# pos

id: cord-003539-tazd6dvm
pos: NNP
token:
  S)-1-(2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-1-oxopropan-2-aminium

lemma:
  S)-1-(2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-1-oxopropan-2-aminium


id: cord-003539-tazd6dvm
pos: NNP
token:
  S)-1-(2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-3-hydroxy-1-oxopropan-2-aminium

lemma:
  S)-1-(2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-3-hydroxy-1-oxopropan-2-aminium


id: cord-003539-tazd6dvm
pos: NNP
token:
  R)-1-(2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-3-methyl-1-oxobutan-2-aminium

lemma:
  R)-1-(2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-3-methyl-1-oxobutan-2-aminium


id: cord-003539-tazd6dvm
pos: CD
token:
  1-(2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-2-methyl-1-oxopropan-2aminium

lemma:
  1-(2-(4,5-dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-2-methyl-1-oxopropan-2aminium


id: cord-003539-tazd6dvm
pos: CD
token:
  3-((2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)carbonyl)oxetan-3-aminium

lemma:
  3-((2-(4,5-dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)carbonyl)oxetan-3-aminium


id: cord-003539-tazd6dvm
pos: NNP
token:
  R)-2-((2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)carbonyl)-pyrrolidinium

lemma:
  R)-2-((2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)carbonyl)-pyrrolidinium


id: cord-003539-tazd6dvm
pos: NN
token:
  S)-2-((2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)carbonyl)-pyrrolidinium

lemma:
  s)-2-((2-(4,5-dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)carbonyl)-pyrrolidinium


id: cord-003539-tazd6dvm
pos: NNP
token:
  R)-2-(2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-2-oxo-1-phenylethanaminium

lemma:
  R)-2-(2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-2-oxo-1-phenylethanaminium


id: cord-003539-tazd6dvm
pos: NNP
token:
  R)-2-(2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-1-(4-hydroxyphenyl)-2-oxoethanaminium

lemma:
  R)-2-(2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-1-(4-hydroxyphenyl)-2-oxoethanaminium


id: cord-003539-tazd6dvm
pos: NN
token:
  S)-2-(2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-1-(4-hydroxyphenyl)-2-oxoethanaminium

lemma:
  s)-2-(2-(4,5-dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-1-(4-hydroxyphenyl)-2-oxoethanaminium


id: cord-003539-tazd6dvm
pos: NNP
token:
  R)-2-(2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-1-(4-fluorophenyl)-2-oxoethanaminium

lemma:
  R)-2-(2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-1-(4-fluorophenyl)-2-oxoethanaminium


id: cord-003539-tazd6dvm
pos: NNP
token:
  S)-2-(2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-1-(4-fluorophenyl)-2oxoethanaminium

lemma:
  S)-2-(2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-1-(4-fluorophenyl)-2oxoethanaminium


id: cord-003539-tazd6dvm
pos: NNP
token:
  R)-1-(2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-3-(4-hydroxyphenyl)-1-oxopropan-2-aminium

lemma:
  R)-1-(2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-3-(4-hydroxyphenyl)-1-oxopropan-2-aminium


id: cord-003539-tazd6dvm
pos: NNP
token:
  S)-1-(2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-3-(4-hydroxyphenyl)-1-oxopropan-2-aminium

lemma:
  S)-1-(2-(4,5-Dihydroxy-7-methyl-9,10-dioxo-9,10-dihydroanthracen-2-yloxy)ethoxy)-3-(4-hydroxyphenyl)-1-oxopropan-2-aminium


id: cord-331504-b68y9hxw
pos: NNP
token:
  trans-(2-methyl-5-(3-(3-nitrobenzyl)-4-oxo-3,4-dihydroquinazolin-2-yl)isoxazolidin-3-yl)-phosphonate

lemma:
  trans-(2-methyl-5-(3-(3-nitrobenzyl)-4-oxo-3,4-dihydroquinazolin-2-yl)isoxazolidin-3-yl)-phosphonate


id: cord-287123-ldkuwcc7
pos: CD
token:
  3-phenyl-1-((R)-1-(3-phenyl-1-((S)-1-(3-phenylureido)propan-2-yl)ureido)hexan-2-yl)-1-(4-phenylbutyl)urea

lemma:
  3-phenyl-1-((r)-1-(3-phenyl-1-((s)-1-(3-phenylureido)propan-2-yl)ureido)hexan-2-yl)-1-(4-phenylbutyl)urea


id: cord-287123-ldkuwcc7
pos: NNP
token:
  R)-4-(cyclohexylmethyl)-5-(4hydroxybenzyl)-1-((R)-1-((S)-2-(((S)-6-isopropyl-2,3-dioxopiperazin-1-yl)methyl)pyrrolidin-1-yl)-3-(naphthalen-2-yl)propan-2-yl)piperazine-2,3-dione

lemma:
  R)-4-(cyclohexylmethyl)-5-(4hydroxybenzyl)-1-((R)-1-((S)-2-(((S)-6-isopropyl-2,3-dioxopiperazin-1-yl)methyl)pyrrolidin-1-yl)-3-(naphthalen-2-yl)propan-2-yl)piperazine-2,3-dione


# ent

id: cord-003329-zhauwxye
type: ORG
entity:
  Investigation of Neuraminidase Substrate Recognition Using Molecular Dynamics and Free Energy Calculations Molecular


id: cord-003329-zhauwxye
type: CHEMICAL
entity:
  Influenza A H2N2 Virus date 2011 08 03 journal Molecules DOI 10 3390 molecules16086489 sha f2d842780b9928cc70f38a4458553f2431877603 doc_id 3329 cord_uid


id: cord-003329-zhauwxye
type: CHEMICAL
entity:
  influenza B viruses Influenza neuraminidase inhibitors Structure based design of a novel inhibitor series On the lower susceptibility of oseltamivir


id: cord-003539-tazd6dvm
type: PROTEIN
entity:
  anti tumour 5 6 7 anti inflammatory 8 9 antiviral 10 antibacterial 11 anti allergic 12 anti osteoporotic 13 anti diabetic 14 15 immunosuppressive 16 neuroprotective 17 and hepatoprotective 18 19


id: cord-003539-tazd6dvm
type: PROTEIN
entity:
  anti tumor anti osteoporotic 13 anti diabetic 14 15 immunosuppressive 16 neuroprotective 17 and hepatoprotective 18 19


id: cord-003539-tazd6dvm
type: GGP
entity:
  NMR S 1 2 4 5 Dihydroxy 7 methyl 9 10 dioxo 9 10 dihydroanthracen 2 yloxy ethoxy 3 hydroxy 1 oxopropan 2 aminium 2 2 2 trifluoroacetate


id: cord-003539-tazd6dvm
type: CHEMICAL
entity:
  give compound 7f Yellow solid 43 s 3H 1 83 1 76 m 2H 1 75 1 68 m 2H 1 56 1 46 m 2H 1 40 d J 7 1 Hz 3H


id: cord-295229-dxl7wvcx
type: PROTEIN
entity:
  intracellular signalling molecules p38 mitogen activated protein kinase nuclear factor κB and c Jun amino terminal kinase


id: cord-257581-trt6s1wp
type: GGP
entity:
  acetyl 7 8 didehydrocimigenol 3 O β D galactopyranoside 1 7 8 didehydrocimigenol 3 O β D galactopyranoside 2


id: cord-003297-fewy8y4a
type: PROTEIN
entity:
  1 protein connexin43 13 SLC8A1 Sodium calcium exchanger 1 11 ATP2A1 Calcium transporting ATPase fast twitch 1 9 KCNH2 Potassium


id: cord-003297-fewy8y4a
type: PROTEIN
entity:
  pLD 50 Fit Score 2V7O Fit Score 2VZ6 6 1 3 3 20 2 1 12 12 3 4 9 1 4 2 4 11 5 7 2 14 6 8 13 16 7 5 6 7 8 17 15 8 9 10 11 27 10 23 17 13 11 12 19 15 12 11 5 32 13 18 18 5 14 22 8 33 15 13 29 21 16 15 1 25 17 9 20 22 18 25 25 17 19 20 16 28 20 24 30 9 21 16 32 29 22 32 14 2 23 30 24 30 24 31 26 18 25 21 27 10 26 26 21 23 27 29 31 31 28 33 7 26 29 14 23 4 30 28 33 3 31 6 10 19 32 27 28 24 33 19 22 NDCG 1 0 9122 0 8503 The


id: cord-003297-fewy8y4a
type: WORK_OF_ART
entity:
  A Comprehensive In Silico Method to Study the QSTR of the Aconitine Alkaloids for Designing Novel Drugs


id: cord-272113-j82z4q8x
type: PROTEIN
entity:
  peptidomimetic alpha beta unsaturated esters Synthesis crystal structure structure activity relationships and antiviral activity of a potent SARS coronavirus 3CL protease


id: cord-003990-15rg623y
type: DISEASE
entity:
  HSV 1 Vaccinia virus para influenza 3 virus Sindbis virus Coxsackie virus Punta toro virus vesicular stomatitis virus VSV Coxsackie virus B4 CV B4 respiratory syncytial virus RSV feline corona virus and feline herpes virus


id: cord-011969-bvun86eh
type: PROTEIN
entity:
  N quinolin 8 yl 4 R benzene sulfonamide metal II QBSC and N quinolin 8 yl quinoline 8 sulfonamide metal II


id: cord-011969-bvun86eh
type: PROTEIN
entity:
  N quinolin 8 yl 4 R benzene sulfonamide metal II QBSC and N quinolin 8 yl quinoline 8 sulfonamide metal II QQSC Scheme 1 Scheme 1


id: cord-011969-bvun86eh
type: ORG
entity:
  Gilman s the Pharmacological Basis of Therapeutics The Organic Chemistry of Drug Design and Drug Action WHO Global Strategy for Containment of Antimicrobial Resistance


id: cord-280292-90i45kjk
type: CHEMICAL
entity:
  phenyl ring C O H bending C C H bending in aryl group C N stretching C C stretching in amide group C O H bending C C H bending in aryl group C N rocking in amide group C O H bending C H rocking C C stretching in aryl group C N H bending in amide group C N stretching C O stretching C C stretching in aryl group C O stretching in amide group symmetrical C H stretching in amide group


id: cord-259985-uysf83sh
type: CHEBI
entity:
  constituents astragaloside calycosin formononetin atractylenolide II cimicifugoside 4 O beta D glucosyl


id: cord-259985-uysf83sh
type: WORK_OF_ART
entity:
  Using UPLC MS MS for Characterization of Active Components in Extracts of Yupingfeng and Application to a Comparative Pharmacokinetic Study in Rat Plasma after Oral Administration


id: cord-259985-uysf83sh
type: WORK_OF_ART
entity:
  Screening for the anti inflammatory activity of fractions and compounds from Atractylodes macrocephala koidz Houshiheisan compound prescription protects neurovascular units after cerebral ischemia Characterization


id: cord-259985-uysf83sh
type: CHEMICAL
entity:
  astragaloside calycosin formononetin atractylenolide II cimicifugoside 4 O beta D glucosyl 5 O methylvisamminol


id: cord-259985-uysf83sh
type: CHEMICAL
entity:
  Astragali radix seven constituents atractylodes lactone class polysaccharide in Atractylodis rhizoma


id: cord-259985-uysf83sh
type: CHEMICAL
entity:
  Astragali radix seven constituents atractylodes lactone class polysaccharide from Atractylodis rhizoma


id: cord-299985-9954q0zg
type: DNA
entity:
  High Fat Diet date 2020 09 27 journal Molecules DOI 10 3390 molecules25194433 sha d124b2fdadc6aee33ddf37a088c22bd76fdd47e3 doc_id 299985 cord_uid 9954q0zg Objective Obesity


id: cord-299985-9954q0zg
type: PROTEIN
entity:
  sterol regulatory element binding protein 1c SREBP 1c peroxisome proliferator activated receptor gamma PPAR


id: cord-299985-9954q0zg
type: PROTEIN
entity:
  pro inflammatory NF κB system EPA and HT co supplementation diminished HFD dependent effects additively reaching values close or similar to controls Conclusion Data presented strengthen the importance of combined protocols such as EPA plus HT


id: cord-299985-9954q0zg
type: DNA
entity:
  5 3 direction Nuclear factor erythroid 2 related factor 2 Nrf2 glutathione S transferase GST glutamate cysteine ligase GCL sterol regulatory element binding protein 1c SREBP 1c fatty acid synthase FAS acetyl CoA carboxylase ACC peroxisome proliferator activated receptor gamma PPAR


id: cord-299985-9954q0zg
type: GGP
entity:
  sterol regulatory element binding protein 1c SREBP 1c peroxisome proliferator activated receptor gamma PPAR γ nuclear factor kappa light chain enhancer


id: cord-299985-9954q0zg
type: GGP
entity:
  sterol regulatory element binding protein 1c SREBP 1c fatty acid synthase FAS acetyl CoA carboxylase ACC peroxisome proliferator activated receptor gamma PPAR γ Fatty acid transport protein 1 FATP1 lipoprotein lipase LPL nuclear factor kappa light chain enhancer


id: cord-299985-9954q0zg
type: WORK_OF_ART
entity:
  Protective Effects of Eicosapentaenoic Acid Plus Hydroxytyrosol Supplementation Against White Adipose Tissue Abnormalities in Mice Fed a High Fat Diet date 2020


id: cord-268902-npug5c8p
type: PROTEIN
entity:
  hepatocyte asialoglycoprotein receptor Human mannose binding protein carbohydrate recognition domain


id: cord-268902-npug5c8p
type: GGP
entity:
  mannose 6 phosphate receptor Herpes simplex virus glycoprotein D acquires mannose 6 phosphate residues


id: cord-003070-6oca1mrm
type: DNA
entity:
  e Caenorhabditis elegans Drosophila melanogaster Escherichia coli Homo sapiens Mus musculus and Saccharomyces cerevisiae


id: cord-003070-6oca1mrm
type: PROTEIN
entity:
  amino acid sequence A Study of Cross Validation and Bootstrap for Accuracy Estimation and Model Selection The noncoding RNAs


id: cord-013412-gj443yei
type: PROTEIN
entity:
  hemagglutinin HA neuraminidase NA matrix protein 1 M1 proton channel protein M2 nucleoprotein NP RNA polymerase PA PB1


id: cord-013412-gj443yei
type: CHEMICAL
entity:
  Cationic tetrakis N methyl 4 pyridiniumyl porphyrin tetrakis N n butyl 4 pyridiniumyl porphyrin tetrakis N n octyl 4 pyridiniumyl porphyrin


id: cord-034363-6uscua0y
type: CHEMICAL
entity:
  indolyl propyl 4 methylbencensulfonate 1b 268 mg 0 72 mmol in CH 3 CN 50 mL 1 7 Fluoro 2 3 dihydro benzo b 1 4 1 4 oxazin 4 yl ethanamide


id: cord-034363-6uscua0y
type: CHEMICAL
entity:
  anhydrous K 2 CO 3 13 s 2H H 6 3 39 q 2H H 8 J 6 4 Hz 3 58 t 4H H 2 J 4 2 Hz 6 96 t 1H H 5 or H 6 J 7 2 Hz 7 06 t 1H H 6 or H 5 Piperazin 1 yl propyl 1H indole 9a


id: cord-280807-0g1uo0rd
type: CHEMICAL
entity:
  Quercetin 3 O glucoside isoquercetin Figure S2 13C spectrum of Quercetin 3 O glucoside isoquercetin DMSO d6 500 MHz Figure S3 1H 13C HMBC of Quercetin 3 O Glucoside isoquercetin DMSO d6 500 MHz Figure S4 Effect of different H noldeae s constituents


id: cord-266149-h8bu3jrq
type: ORG
entity:
  the Solid State Para Hydrogen Induced Polarization PHIP Para Hydrogen Induced Polarization in Hydrogenation Reactions Reversible Interactions


id: cord-266149-h8bu3jrq
type: FAC
entity:
  Organic Reaction Monitoring of a Glycine Derivative Using Signal Amplification by Reversible Exchange Hyperpolarized Benchtop Nuclear Magnetic Resonance Spectroscopy Strategies


id: cord-264326-teahway7
type: PROTEIN
entity:
  RNA polymerase DPP 4 dipeptidyl peptidase 4 COVID 19 Outbreak Situation COVID 19 Coronavirus Pandemic


id: cord-289288-46nyje11
type: DNA
entity:
  Homonucleosides date 2019 11 06 journal Molecules DOI 10 3390 molecules24224014 sha 8a2ca0a9b9108a56a79d6a610c6537102c124697 doc_id 289288 cord_uid 46nyje11


id: cord-289288-46nyje11
type: CELL_LINE
entity:
  human embryonic lung HEL cell cultures herpes simplex virus 1 KOS strain herpes simplex virus 2 G strain vaccinia virus thymidine kinase deficient acyclovir resistant herpes simplex virus 1 TK KOS ACV r adenovirus 2 human coronavirus 229E strain cytomegalovirus AD 169


id: cord-289288-46nyje11
type: CELL_LINE
entity:
  1 pancreatic adenocarcinoma Hap1 chronic myeloid leukemia HCT 116 colorectal carcinoma NCI H460 lung carcinoma DND 41 acute lymphoblastic leukemia HL 60 acute myeloid leukemia K 562 chronic myeloid leukemia MM 1S multiple myeloma and Z 138 non Hodgkin lymphoma


id: cord-289288-46nyje11
type: PROTEIN
entity:
  C3 1 73 ddd 1H 2 J H3β H3α 13 4 Hz 3 J H3β H4 7 0 Hz C O 171 29 C4 154 26 C2 68 99 C4 55 97 CH 2 dihydroUra Yield 34


id: cord-289288-46nyje11
type: DISEASE
entity:
  influenza B virus Ganciclovir cidofovir acyclovir brivudin zalcitabine zanamivir alovudine mycophenolic acid amantadine rimantadine ribavirin dextran sulfate


id: cord-289288-46nyje11
type: CHEMICAL
entity:
  Ganciclovir cidofovir acyclovir brivudin zalcitabine zanamivir alovudine mycophenolic acid amantadine rimantadine ribavirin dextran sulfate


id: cord-289288-46nyje11
type: CHEMICAL
entity:
  s 3H CH 3 3 44 s 3H CH 3 2 96 s 3H 36 C4 141 63 C8 106 83 C5 69 26 C4 57 75 CH 2 The Yield 28 a colorless amorphous solid m p 230 C


id: cord-289288-46nyje11
type: CHEMICAL
entity:
  s 3H CH 3 N 2 27 2 23 m 1H H α C3 1 45 dt 1H 2 J 14 2 Hz 3 J 7 0 Hz H β C3 Synthesis of γ Lactams cis 15d


id: cord-256838-8rzibpbl
type: WORK_OF_ART
entity:
  Unraveling the Molecular Mechanism of Traditional Chinese Medicine Formulas Against Acute Airway Viral Infections as Examples


id: cord-256838-8rzibpbl
type: CHEMICAL
entity:
  1 2 3 4 6 penta O galloyl β D glucopyranose from Paeonia lactiflora show antiviral activity against rhinovirus 57 Of its anti inflammatory


id: cord-256838-8rzibpbl
type: CHEMICAL
entity:
  1 2 3 4 6 penta O galloyl β d glucopyranose from Paeonia lactiflora show antiviral activity against rhinovirus 57 Of its anti inflammatory


id: cord-256838-8rzibpbl
type: CHEMICAL
entity:
  Aristolochia fangchi Aristolochia debilis Sieb et Zucc Aristolochia manshuriensis Aristolochia debilis


id: cord-290855-6umgvt28
type: ORG
entity:
  Antioxidant and Immunomodulatory Properties of Essential Oils A Systematic Review Chemical Composition


id: cord-324829-0nz0qioh
type: PROTEIN
entity:
  gp120 V3 Loop Peptide Toward Fully Synthetic HIV Vaccine Candidates Surface Engineered Gold Nanorods Promising DNA Vaccine Adjuvant for HIV 1


id: cord-324829-0nz0qioh
type: ORG
entity:
  Tracking Targeted Bimodal Nanovaccines Immune Responses and Routing in Cells Tissue and Whole Organism Protection of non


id: cord-003427-0dddrh4e
type: PROTEIN
entity:
  anti microbial 2 3 4 anti mycobacterial 5 6 anti convulsant 7 analgesic 8 anti inflammatory 9 anti platelet


id: cord-306633-69ljgkqy
type: CELL_LINE
entity:
  Madin Darby canine kidney MDCK influenza A H1N1 H3N2 and influenza B cell cultures Confluent cell cultures


id: cord-281281-knelqmzx
type: WORK_OF_ART
entity:
  Function and Antigenicity of the SARS Structure Function and Antigenicity of the SARS CoV 2 Spike Glycoprotein Dysregulated Type


id: cord-331504-b68y9hxw
type: PROTEIN
entity:
  J H3 H4α 9 3 Hz 41 J H3 H4β 8 3 Hz J H4α P 9 9 Hz 42 43 J H4β P 16 9 Hz J H4α H5 6 2 Hz J H4β H5 8 3 Hz J CCCP 8 5 Hz 44 45


id: cord-331504-b68y9hxw
type: PROTEIN
entity:
  C4 J H3 H4β 7 7 Hz 2 J H3 P 2 7 Hz 1H HC3 2 79 dddd 3 J H4β P 15 4 Hz 2 J H4β H4α 12 7 Hz J H4β H3 7 7 Hz 3 J H4β H5 7 7 Hz 1H H β C4 37 d 3 J CCCP 7 8 Hz C5 64 38 d 1 J CP 170 6 Hz C3 63 02 d 2 J COP 6 6


id: cord-331504-b68y9hxw
type: PROTEIN
entity:
  camphan zur Bestimmung von 3 J CCCP Vicinalkopplungen 13 C and 31 P NMR spectra of 1 diethylphosphono 1


id: cord-331504-b68y9hxw
type: CHEMICAL
entity:
  2 vinyl 3H quinazolin 4 ones 13 substituted at N3 Scheme 1 Scheme 1 Retrosynthesis of isoxazolidinyl phosphonates trans 11 cis 11 2 Vinyl 3H quinazolin 4 ones


id: cord-331504-b68y9hxw
type: CHEMICAL
entity:
  Ganciclovir cidofovir acyclovir brivudin zalcitabine zanamivir alovudine amantadine rimantadine ribavirin dextran sulfate


id: cord-331504-b68y9hxw
type: CHEMICAL
entity:
  phosphonates Ganciclovir cidofovir acyclovir brivudin zalcitabine zanamivir alovudine amantadine rimantadine ribavirin dextran sulfate


id: cord-331504-b68y9hxw
type: CHEMICAL
entity:
  eluents Diethyl trans 2 methyl 5 4 oxo 3 4 dihydroquinazolin 2 yl isoxazolidin 3 yl phosphonate trans 11a Yellowish oil IR


id: cord-331504-b68y9hxw
type: CHEMICAL
entity:
  3085 2980 2929 2782 1687 1610 1469 1331 1132 1098 1052 13 Diethyl trans 2 methyl 5 3 3 nitrobenzyl 4 oxo 3 4 dihydroquinazolin 2 yl isoxazolidin 3 yl phosphonate trans 11d


id: cord-331504-b68y9hxw
type: CHEMICAL
entity:
  s 3H CH 3 N 3 10 2 96 m 2H H α C4 H β C4 1 55 t 3 J 7 1 Hz 3H CH 3 CH 2 1 42 t 3 J 7 0 Hz 3H CH 3 CH 2 OP 1 39 t 3 J 7 1 Hz 3H CH 3 CH 2 OP 13 C NMR 151 MHz


id: cord-331504-b68y9hxw
type: CHEMICAL
entity:
  E 2 1 4 Dimethylpiperazin 2 ylidene amino 5 nitro Nphenylbenzamide ML336 Novel 2 Amidinophenylbenzamides


id: cord-268088-y4vg7frb
type: CELL_TYPE
entity:
  human tumors breast skin ovary stomach prostate colon liver pancreas cervix thyroid carcinoma cells lymphoid and myeloid cancer cells


id: cord-268088-y4vg7frb
type: CELL_TYPE
entity:
  colorectal cancer cells 92 93 U S Department of Health and Human Services Public Health Service Food


id: cord-268088-y4vg7frb
type: ORG
entity:
  Caspase 3 U S Department of Health and Human Services Public Health Service Food and Drug Administration Status Bulk


id: cord-268088-y4vg7frb
type: ORG
entity:
  U S Department of Health and Human Services Public Health Service Food and Drug Administration Status Drug


id: cord-310268-8q4tk6fd
type: DNA
entity:
  3390 molecules201219739 sha 8d0dc902f68228a84345abe956a41bb58ea01ef3 doc_id 310268 cord_uid 8q4tk6fd Aptamers


id: cord-310268-8q4tk6fd
type: ORG
entity:
  Myoglobin Using a Positive and Negative Selection Units Integrated Microfluidic Chip and Its Biosensing Application Development


id: cord-313668-zz32fpvz
type: DISEASE
entity:
  Aspergillus sp SCSIO XWS02F40 21 22 Thus this establishes the absolute configuration of C 12 to be S Thus the structure of compound 4 was determined and named as 7 hydroxy 2 2hydroxypropyl


id: cord-276781-ujvkcz4s
type: CHEMICAL
entity:
  s 3H CH 3 CO 2 11 s 3H CH 3 CO 2 16 s 3H 65 dd 1H H 5 J 5 4 1 9 Hz J 5 5 12 5 Hz 5 39 dd 1H H 3 J 3 4 3 2 Hz J 3 2 6 2 Hz 5 47 m 1H H 2 5 89 d 1H H 1 J 1 2 7 5 Hz 7 47 br s 2H D 2 O exchangeable NH 2 7 52 s 1H H 7 13 C NMR 151 MHz CDCl 3 δ 20 36 CH 3 CO 20 65 CH 3 CO β d ribofuranosyl 3H imidazo 4 5 b pyridin 2 amine


id: cord-284113-qboon2uv
type: PROTEIN
entity:
  G and Gbacteria and yeast and the effect depended on the cultivar and seeding date 14 This study addresses a knowledge gap and current industry interest


id: cord-309722-04pp3lv0
type: PROTEIN
entity:
  stem cell factor receptor DCs dendritic cells HMGB1A high mobility group box 1 A peptide IFU infectious unit LPS lipopolysaccharide Mpl myeloproliferative leukemia virus oncogene OVA


id: cord-309722-04pp3lv0
type: PROTEIN
entity:
  cytokine signaling protein 3 STAT6 signal transducer and activator of transcription factor 6 Syk spleen tyrosine kinase Tf


id: cord-309722-04pp3lv0
type: DNA
entity:
  miR 1 Mpl myeloproliferative leukemia virus oncogene P selectin axis Receptor interacting protein 2 gene


id: cord-309722-04pp3lv0
type: CL
entity:
  stem and two loops and is claimed to be stable against nuclease degradation Inhibition of lung tumor growth was observed without any signs of toxicity after treatment The antitumor effect was triggered by PnkRNA targeting RPN2 without


id: cord-272465-i2l4cq8h
type: GGP
entity:
  Alzheimer s disease Inositol and IP3 levels regulate autophagy Biology and therapeutic speculations Lithium


id: cord-272465-i2l4cq8h
type: CHEMICAL
entity:
  Nelumbo nucifera Syzygium samarangense Mallotus philippensis Rhizoma anemarrhenae Radix glehniae Radix ophiopogonis Radix glycyrrhizae Radix dipsaci Radix ginseng Radix codonopsis Rhizoma


id: cord-272465-i2l4cq8h
type: CHEMICAL
entity:
  Rhizoma alismatis Cortex magnoliae officinalis Fructus piperis longi Radix salviae miltiorrhizae Rhizoma chuanxiong Garcinia hanburyi Radix


id: cord-272465-i2l4cq8h
type: DISEASE
entity:
  neurodegenerative disorders Nelumbo nucifera Mallotus philippensis Rhizoma anemarrhenae Radix ginseng Radix tripterygii wilfordii


id: cord-272465-i2l4cq8h
type: CHEMICAL
entity:
  bangladeshi fruits Artocarpus heterophyllus Annona squamosa Terminalia bellirica Syzygium samarangense Averrhoa carambola and Olea europa


id: cord-300872-blycbi4u
type: CHEMICAL
entity:
  umbelliferone 8hydroxyquinoline n 2 umbelliferone 8 hydroxyquinoline n 4 and umbelliferone 4hydroxyquinoline n


id: cord-330253-9sqizkio
type: ORG
entity:
  degradation kinetic study Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research CDER Center for Veterinary Medicine CVM Ethnic


id: cord-330253-9sqizkio
type: CHEMICAL
entity:
  glucagon like peptide 1 GLP 1 increasing insulin secretion Contrary to the once daily administered DPP 4 inhibitors


id: cord-302190-co4tju7u
type: WORK_OF_ART
entity:
  A Review on the Phytochemistry Pharmacology and Pharmacokinetics of Amentoflavone a Naturally Occurring Biflavonoid


id: cord-302190-co4tju7u
type: CHEMICAL
entity:
  Gingko biloba Lobelia chinensis Polygala sibirica Ranunculus ternatus Selaginella pulvinata Selagenella


id: cord-287754-dh6abx2t
type: GGP
entity:
  concanavalin A 26 Urtica diocia agglutinin 27 Myrianthus holstii lectin P tetragonolobus lectin 28 and Narcissus pseudonarcissus lectin


id: cord-352513-15nalst7
type: ORG
entity:
  Active Digital Microfluidic Paper Chips with Inkjet Printed Patterned Electrodes Paper microfluidics


id: cord-352513-15nalst7
type: ORG
entity:
  HPV Oligonucleotides Semiquantitative Nucleic Acid Test with Simultaneous Isotachophoretic Extraction and Amplification Simpler Faster and


id: cord-276598-tm0yj2sn
type: PROTEIN
entity:
  Zur Umsetzung des Zweikomponentensystems Trialkylphosphit Tetrachlorkohlenstoff mit wasserstoffhaltigen Nucleophilen 2 Die Reaktion mit Ammoniak


id: cord-276598-tm0yj2sn
type: WORK_OF_ART
entity:
  Anchimerically Activatable Antiviral ProTides New and Efficient Approach to Aryl Phosphoramidate Derivatives of AZT


id: cord-276598-tm0yj2sn
type: CHEMICAL
entity:
  bromomethyl benzene 1 bromomethyl 2 nitrobenzene 1 chloromethyl 4 nitrobenzene chloromethyl benzene 1 bromomethyl 3 5 dimethoxybenzene or 3 4 bromomethyl 1H 1 2 3 triazol 1 yl benzyl acetate


id: cord-276598-tm0yj2sn
type: CHEMICAL
entity:
  dimethyl or diethyl H P 1 chloromethyl 4 nitrobenzene chloromethyl benzene 1 bromomethyl 3 5 dimethoxybenzene or 3 4 bromomethyl 1H 1 2 3 triazol 1 yl benzyl acetate


id: cord-355685-wgad0eoh
type: CELL_LINE
entity:
  mammalian cell culture assays 24 25 26 27 The antiviral activity data obtained by microscopic inspection of the viral CPE


id: cord-355685-wgad0eoh
type: WORK_OF_ART
entity:
  Functionalized Benzimidazole Scaffolds Privileged Heterocycle for Drug Design in Therapeutic Medicine


id: cord-355685-wgad0eoh
type: CHEMICAL
entity:
  s 1H NH 2 4 33 s 2H CH 2 Ar 4 17 pseudo s 2H CH 2 CH 2 CH 2 N CH 2 CH 3 2 2 47 2 27 m superimposed 6H 2H CH 2 CH 2 CH 2 N CH 2 CH 3 2 and 4H CH 2 CH 2 N CH 2 CH 3 2 2 26 s superimposed 3H CH 3 C N 1 62 pseudo s 2H CH 2 CH 2 CH 2 N CH 2 CH 3 2 0 90 pseudo s 6H N CH 2 CH 3 2 13 C


id: cord-355685-wgad0eoh
type: CHEMICAL
entity:
  s 2H NH 2 4 25 s 2H CH 2 Ar 4 22 4 07 m superimposed 2H CH 2 CH 2 CH 2 N CH 2 CH 3 2 3 71 s 3H OCH 3 2 46 2 20 m superimposed 6H 2H CH 2 CH 2 CH 2 N CH 2 CH 3 2 and 4H N CH 2 CH 3 2 2 26 s 3H CH 3 C N 15 2C Anal calcd


id: cord-307731-a2fqmaly
type: PROTEIN
entity:
  GPER 1 selective agonist 1 3aR 4S 9bS 4 6 bromobenzo d 1 3 dioxol 5 yl 3a 4 5 9b tetrahydro 3H cyclopenta c quinolin


id: cord-307731-a2fqmaly
type: PROTEIN
entity:
  dihydrofolate reductase glucocorticoid receptor HIV 1 protease vascular endothelial growth factor receptor 2 adenosine A2A receptor


id: cord-334511-lx9608vy
type: DNA
entity:
  High Fat Diet Pharmacometabonomics Analysis Reveals Serum Formate and Acetate Potentially Associated with Varying Response to Gemcitabine Carboplatin Chemotherapy


id: cord-334511-lx9608vy
type: DNA
entity:
  Nuclear Magnetic Resonance Experiment Part II Pulse and Fourier Transform NMR Spin Lattice Relaxation Time in Drug Discovery and Design NMR Methods to Characterize Protein Ligand


id: cord-334511-lx9608vy
type: GGP
entity:
  nuclei i e 13 C 146 thereby reducing the time needed for the acquisition of spectra 147 Heteronuclear Single Quantum Coherence HSQC


id: cord-334511-lx9608vy
type: ORG
entity:
  Solvent and Anion Dependent Li O2 Coupling Strength and Implications on the Thermodynamics and Kinetics of Li O2 Batteries


id: cord-334511-lx9608vy
type: ORG
entity:
  NMR Spectroscopy Study of Heavy Fuel Oil Recommendations and Standardization of Biomarker Quantification


id: cord-334511-lx9608vy
type: PRODUCT
entity:
  Chemoselective 15N Tag for Sensitive and High Resolution Nuclear Magnetic Resonance Profiling of the Carboxyl Containing Metabolome 15N Cholamine A


id: cord-334511-lx9608vy
type: ORG
entity:
  An Improved 15N Relaxation Dispersion Experiment for the Measurement of Millisecond Time Scale Dynamics


id: cord-334511-lx9608vy
type: ORG
entity:
  Metabonomic Profiles Delineate the Effect of Traditional Chinese Medicine Sini Decoction on Myocardial Infarction


id: cord-334511-lx9608vy
type: ORG
entity:
  Virtual High Throughput Screening Using Machine Learning Methods Introduction to Fragment Based Drug Discovery


id: cord-334511-lx9608vy
type: ORG
entity:
  High Throughput Screening and Fragment Based Design General Considerations for Lead Discovery and Optimization NMR Screening and Hit Validation in Fragment Based Drug Discovery Structural


id: cord-334511-lx9608vy
type: WORK_OF_ART
entity:
  Fragment Based Drug Discovery Using NMR Spectroscopy Chapter Nine Practical Aspects of NMR Based Fragment Screening Fragment Based Drug Design


id: cord-334511-lx9608vy
type: ORG
entity:
  Krimm I Fragment Linking Strategies for Structure Based Drug Design Discovery and Development of Venetoclax a Selective Antagonist


id: cord-334511-lx9608vy
type: ORG
entity:
  Development of Second Generation CDK2 Inhibitors for the Prevention of Cisplatin Induced Hearing Loss Practical Fragments Fragments


id: cord-334511-lx9608vy
type: WORK_OF_ART
entity:
  DOSY NMR Open Chem Structure Based Virtual Screening for Drug Discovery Principles Applications and Recent Advances


id: cord-334511-lx9608vy
type: ORG
entity:
  Ultra High Throughput Structure Based Virtual Screening for Small Molecule Inhibitors of Protein Protein Interactions


id: cord-334511-lx9608vy
type: ORG
entity:
  Screening Acceleration of the Drug Discovery Process A Combinatorial Approach Using NMR Spectroscopy and Virtual Screening Complementarity between


id: cord-334511-lx9608vy
type: WORK_OF_ART
entity:
  Using Ligand Induced Protein Chemical Shift Perturbations To Determine Protein Ligand Structures Automatic


id: cord-334511-lx9608vy
type: ORG
entity:
  Inventions A Review of Nondestructive Characterization of Composites Using NMR Chapter 2 Mass Spectrometry Dehydrodimerization


id: cord-334511-lx9608vy
type: CHEMICAL
entity:
  methyl group 1 of ligand 1 aromatic proton 8 of ligand 2 and aromatic proton 8 of ligand 1 exhibit strong water NOE This information enabled


id: cord-334511-lx9608vy
type: CHEMICAL
entity:
  2 4 Dihydroxy 5 isopropylphenyl 5 4 methylpiperazin 1 ylmethyl 1 3 dihydroisoindol 2 yl methanone AT13387


id: cord-287123-ldkuwcc7
type: CHEMICAL
entity:
  N substituted benzimidazoles pyridazin 3 2H ones chiral pyridazines N phenylureas chiral 3 1H indol 3 yl 2 3 4 nitrophenyl ureido propanamides 2 N Piperazinyl acetamide derivatives quinazolinones


id: cord-281668-960trqex
type: PROTEIN
entity:
  Human Cathepsin L date 2020 02 06 journal Molecules DOI 10 3390 molecules25030698 sha c11eac2f07f5ad430230013f3eba74ff74a5c8a2 doc_id 281668 cord_uid 960trqex Human cathepsin L


id: cord-281668-960trqex
type: PROTEIN
entity:
  N peptidyl O acyl hydroxylamines Novel N peptidyl O acyl hydroxamates Selective inhibitors of cysteine proteinases N peptidyl O carbamoyl amino acid hydroxamates Irreversible inhibitors


id: cord-281668-960trqex
type: PROTEIN
entity:
  Cathepsin L Inhibitors Synthesis and biological evaluation of a water soluble phosphate prodrug salt


id: cord-281668-960trqex
type: GGP
entity:
  tick s survival 45 In addition it also possess a potent anti inflammatory and immunosuppressive activity by inhibiting cytotoxic killer T cells


id: cord-281668-960trqex
type: ORG
entity:
  Fluorine Scan of Inhibitors of the Cysteine Protease Human Cathepsin L Dipolar and Quadrupolar Effects


id: cord-281668-960trqex
type: ORG
entity:
  A Combined Crystallographic and Molecular Dynamics Study of Cathepsin L Retrobinding Inhibitors Identification


# bib

id: cord-002026-wybmer7o
title: HTS-Driven Discovery of New Chemotypes with West Nile Virus Inhibitory Activity
author: Chung, Dong Hoon
date: 2010-03-12
txt: ./txt/cord-002026-wybmer7o.txt
cache: ./cache/cord-002026-wybmer7o.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839297/
doi: 10.3390/molecules15031690
summary:
  We developed a high throughput screen to discover small molecule probes that inhibit virus infection of Vero E6 cells. Twenty-six compounds showed a dose response in the HT screen and were further evaluated in a time of addition assay and in a titer reduction assay. To confirm the activity and to test the cytotoxicity, the top 110 inhibitory compounds were evaluated in a dose response assay using the identical screen. All seven compounds screened in the time of addition experiment were confirmed to have anti-WNV activity based on the titer reduction assay and EC 90 values between 2.14~26.16 µM. None of the compounds showed anti-WNV activity as good as the positive control drug, MPA, however, the mechanism of MPA is not specific to the virus making the probes we identified of significant interest. The serially diluted compounds were also used for time of addition studies adding to the infected cells in 384-well plates at -1, 4, 8 and18 h post-infection with WNV (0.02 MOI).

abstract:
  West Nile virus (WNV) is a positive sense, single-stranded RNA virus that can cause illness in humans when transmitted via mosquito vectors. Unfortunately, no antivirals or vaccines are currently available, and therefore efficient and safe antivirals are urgently needed. We developed a high throughput screen to discover small molecule probes that inhibit virus infection of Vero E6 cells. A primary screen of a 13,001 compound library at a 10 μM final concentration was conducted using the 384-well format. Z′ values ranged from 0.54–0.83 with a median of 0.74. Average S/B was 17 and S/N for each plate ranged from 10.8 to 23.9. Twenty-six compounds showed a dose response in the HT screen and were further evaluated in a time of addition assay and in a titer reduction assay. Seven compounds showed potential as small molecule probes directed at WNV. The hit rate from the primary screen was 0.185% (24 compounds out of 13,001 compounds) and from the secondary screens was 0.053% (7 out of 13,001 compounds) respectively.


id: cord-003070-6oca1mrm
title: RPiRLS: Quantitative Predictions of RNA Interacting with Any Protein of Known Sequence
author: Shen, Wen-Jun
date: 2018-02-28
txt: ./txt/cord-003070-6oca1mrm.txt
cache: ./cache/cord-003070-6oca1mrm.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017498/
doi: 10.3390/molecules23030540
summary:
  On the non-redundant benchmark test sets extracted from the PRIDB, the RPiRLS method outperformed RPI-Pred and IPMiner in terms of accuracy, specificity and sensitivity. The computational results showed that the RPiRLS classifier outperformed the RPiRLS-7G classifier in terms of various performance measurements, indicating that the diversity of amino acids at a sequence is important for the prediction of RPIs. The performance of predicting RPIs was evaluated by using 10-fold stratified cross-validation on the RPI2662 data set. For the RPI369 data set as shown in Table 4 , the performance of the RPiRLS method was 0.85, 0.92, 0.84 and 0.86 for predictive accuracy, AUC, specificity and sensitivity, respectively. The work presented here provided a computational method, called RPiRLS, to classify RNA-protein pairs as interacting or non-interacting by integrating a sequence-based derived kernel with regularized least squares.

abstract:
  RNA-protein interactions (RPIs) have critical roles in numerous fundamental biological processes, such as post-transcriptional gene regulation, viral assembly, cellular defence and protein synthesis. As the number of available RNA-protein binding experimental data has increased rapidly due to high-throughput sequencing methods, it is now possible to measure and understand RNA-protein interactions by computational methods. In this study, we integrate a sequence-based derived kernel with regularized least squares to perform prediction. The derived kernel exploits the contextual information around an amino acid or a nucleic acid as well as the repetitive conserved motif information. We propose a novel machine learning method, called RPiRLS to predict the interaction between any RNA and protein of known sequences. For the RPiRLS classifier, each protein sequence comprises up to 20 diverse amino acids but for the RPiRLS-7G classifier, each protein sequence is represented by using 7-letter reduced alphabets based on their physiochemical properties. We evaluated both methods on a number of benchmark data sets and compared their performances with two newly developed and state-of-the-art methods, RPI-Pred and IPMiner. On the non-redundant benchmark test sets extracted from the PRIDB, the RPiRLS method outperformed RPI-Pred and IPMiner in terms of accuracy, specificity and sensitivity. Further, RPiRLS achieved an accuracy of 92% on the prediction of lncRNA-protein interactions. The proposed method can also be extended to construct RNA-protein interaction networks. The RPiRLS web server is freely available at http://bmc.med.stu.edu.cn/RPiRLS.


id: cord-003297-fewy8y4a
author: Wang, Ming-Yang
date: 2018-09-18
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225272/
doi: 10.3390/molecules23092385
title:
  A Comprehensive In Silico Method to Study the QSTR of the Aconitine Alkaloids for Designing Novel Drugs

abstract:
  A combined in silico method was developed to predict potential protein targets that are involved in cardiotoxicity induced by aconitine alkaloids and to study the quantitative structure–toxicity relationship (QSTR) of these compounds. For the prediction research, a Protein-Protein Interaction (PPI) network was built from the extraction of useful information about protein interactions connected with aconitine cardiotoxicity, based on nearly a decade of literature and the STRING database. The software Cytoscape and the PharmMapper server were utilized to screen for essential proteins in the constructed network. The Calcium-Calmodulin-Dependent Protein Kinase II alpha (CAMK2A) and gamma (CAMK2G) were identified as potential targets. To obtain a deeper insight on the relationship between the toxicity and the structure of aconitine alkaloids, the present study utilized QSAR models built in Sybyl software that possess internal robustness and external high predictions. The molecular dynamics simulation carried out here have demonstrated that aconitine alkaloids possess binding stability for the receptor CAMK2G. In conclusion, this comprehensive method will serve as a tool for following a structural modification of the aconitine alkaloids and lead to a better insight into the cardiotoxicity induced by the compounds that have similar structures to its derivatives.


id: cord-003329-zhauwxye
author: Wu, Huaxing
date: 2011-08-03
txt: ./txt/cord-003329-zhauwxye.txt
cache: ./cache/cord-003329-zhauwxye.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264369/
doi: 10.3390/molecules16086489
summary:
  Flexible docking and molecular dynamic simulations indicated that patchouli alcohol was bound to the neuraminidase protein of influenza virus, with an interaction energy of –40.38 kcal mol(–1). Therefore, the aim of the present study was to evaluate the anti-influenza A virus (H2N2) activity of patchouli alcohol by MTT assay and mouse influenza model. On such basis, explicitly solvated docking and molecular dynamic (MD) methods were applied to investigative the binding mode involving patchouli alcohol with influenza virus NA protein. Until now, it has been found that patchouli alcohol showed dose-dependent anti-influenza virus (A/PR/8/34, H1N1) activity, with an IC 50 value of 2.635 µM. As shown in Figure 2 , patchouli alcohol showed anti-influenza A (H2N2) virus activity in a timedependent manner. For pretreatment virus, Influenza A (H2N2) was incubated in medium containing patchouli alcohol for 1h at room temperature prior to infection of MDCK cells.

title:
  Inhibitory Effect and Possible Mechanism of Action of Patchouli Alcohol against Influenza A (H2N2) Virus

abstract:
  In the present study, the anti-influenza A (H2N2) virus activity of patchouli alcohol was studied in vitro, in vivo and in silico. The CC(50) of patchouli alcohol was above 20 µM. Patchouli alcohol could inhibit influenza virus with an IC(50) of 4.03 ± 0.23 µM. MTT assay showed that the inhibition by patchouli alcohol appears strongly after penetration of the virus into the cell. In the influenza mouse model, patchouli alcohol showed obvious protection against the viral infection at a dose of 5 mg/kg/day. Flexible docking and molecular dynamic simulations indicated that patchouli alcohol was bound to the neuraminidase protein of influenza virus, with an interaction energy of –40.38 kcal mol(–1). The invariant key active-site residues Asp151, Arg152, Glu119, Glu276 and Tyr406 played important roles during the binding process. Based on spatial and energetic criteria, patchouli alcohol interfered with the NA functions. Results presented here suggest that patchouli alcohol possesses anti-influenza A (H2N2) virus properties, and therefore is a potential source of anti-influenza agents for the pharmaceutical industry.


id: cord-003341-z5w56zeq
title: In Vitro Evaluation of Novel Inhibitors against the NS2B-NS3 Protease of Dengue Fever Virus Type 4
author: Nguyen, Thi Thanh Hanh
date: 2013-12-13
txt: ./txt/cord-003341-z5w56zeq.txt
cache: ./cache/cord-003341-z5w56zeq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269914/
doi: 10.3390/molecules181215600
summary:
  Virtual screening of 300,000 compounds using Autodock 3 on the GVSS platform was conducted to identify novel inhibitors against the NS2B-NS3(pro). pastoris DENV4 NS2B-NS3 pro , fused to the α-factor secretion signal sequence and placed under the control of the methanol inducible alcohol oxidase promoter, was constructed to express the secreted protein in P. Thirty-six compounds were selected for in vitro assay based on their free energy binding (Table S1 ) and H-bonds interactions with amino acid residues at the NS3 pro active site. Among 300,000 compounds, 36 were selected for testing in vitro inhibitory activity against NS2B-NS3 pro based on hydrogen bond interactions [25, 36] . Activity of recombinant dengue 2 virus NS3 protease in the presence of a truncated NS2B co-factor, small peptide substrates, and inhibitors Novel dengue virus-specific NS2B/NS3 protease inhibitor, BP2109, discovered by a high-throughput screening assay

abstract:
  The discovery of potent therapeutic compounds against dengue virus is urgently needed. The NS2B-NS3 protease (NS2B-NS3(pro)) of dengue fever virus carries out all enzymatic activities needed for polyprotein processing and is considered to be amenable to antiviral inhibition by analogy. Virtual screening of 300,000 compounds using Autodock 3 on the GVSS platform was conducted to identify novel inhibitors against the NS2B-NS3(pro). Thirty-six compounds were selected for in vitro assay against NS2B-NS3(pro) expressed in Pichia pastoris. Seven novel compounds were identified as inhibitors with IC(50) values of 3.9 ± 0.6–86.7 ± 3.6 μM. Three strong NS2B-NS3(pro) inhibitors were further confirmed as competitive inhibitors with K(i) values of 4.0 ± 0.4, 4.9 ± 0.3, and 3.4 ± 0.1 μM, respectively. Hydrophobic and hydrogen bond interactions between amino acid residues in the NS3(pro) active site with inhibition compounds were also identified.


id: cord-003342-wmmbkmrg
title: Two Methods for Increased Specificity and Sensitivity in Loop-Mediated Isothermal Amplification
author: Wang, De-Guo
date: 2015-04-07
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272222/
doi: 10.3390/molecules20046048
abstract:
  The technique of loop-mediated isothermal amplification (LAMP) utilizes four (or six) primers targeting six (or eight) regions within a fairly small segment of a genome for amplification, with concentration higher than that used in traditional PCR methods. The high concentrations of primers used leads to an increased likelihood of non-specific amplification induced by primer dimers. In this study, a set of LAMP primers were designed targeting the prfA gene sequence of Listeria monocytogenes, and dimethyl sulfoxide (DMSO) as well as Touchdown LAMP were employed to increase the sensitivity and specificity of the LAMP reactions. The results indicate that the detection limit of this novel LAMP assay with the newly designed primers and additives was 10 fg per reaction, which is ten-fold more sensitive than a commercial Isothermal Amplification Kit and hundred-fold more sensitive than previously reported LAMP assays. This highly sensitive LAMP assay has been shown to detect 11 strains of Listeria monocytogenes, and does not detect other Listeria species (including Listeria innocua and Listeria invanovii), providing some advantages in specificity over commercial Isothermal Amplification Kits and previously reported LAMP assay.


id: cord-003344-rhld75dy
title: Discovery of Metal Ions Chelator Quercetin Derivatives with Potent Anti-HCV Activities
author: Zhong, Dongwei
date: 2015-04-16
txt: ./txt/cord-003344-rhld75dy.txt
cache: ./cache/cord-003344-rhld75dy.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272327/
doi: 10.3390/molecules20046978
summary:
  Analogues or isosteres of α,γ-diketoacid (DKA) 1a show potent inhibition of hepatitis C virus (HCV) NS5B polymerase through chelation of the two magnesium ions at the active site. Hence, this paper also described a series of novel quercetin-3-O-benzoic acid esters (compounds 4, Figure 2 ) in an attempt to investigate whether the introduction of another carbonyl group at 3-position would result in an improved anti-HCV activity. The maintenance of anti-HCV activities for quercetin-3-O-benzoic acid-ester derivatives instead of the 3-O-aliphatic substituents revealed that the introduction of an electronegative carbonyl group at 3-O position could enhance the chelation ability between the inhibitor and metal ions, which contribute to the binding affinity in a similar way as the 3-hydroxyl group. To rationalize the observed activities of different substituents of quercetin and investigate the binding modes with NS5B, docking calculations were performed on the basis of the reported X-ray crystallographic structure of HCV genotype 1b RdRp complexed with uridine triphosphate (UTP) and divalent metal ions (PDB code: 1GX6 [22] ).

abstract:
  Analogues or isosteres of α,γ-diketoacid (DKA) 1a show potent inhibition of hepatitis C virus (HCV) NS5B polymerase through chelation of the two magnesium ions at the active site. The anti-HCV activity of the flavonoid quercetin (2) could partly be attributed to it being a structural mimic of DKAs. In order to delineate the structural features required for the inhibitory effect and improve the anti-HCV potency, two novel types of quercetin analogues, 7-O-arylmethylquercetins and quercetin-3-O-benzoic acid esters, were designed, synthesized and evaluated for their anti-HCV properties in cell-based assays. Among the 38 newly synthesized compounds, 7-O-substituted derivative 3i and 3-O-substituted derivative 4f were found to be the most active in the corresponding series (EC(50) = 3.8 μM and 9.0 μΜ, respectively). Docking studies suggested that the quercetin analogues are capable of establishing key coordination with the two magnesium ions as well as interactions with residues at the active site of HCV NS5B.


id: cord-003427-0dddrh4e
author: El-Faham, Ayman
date: 2015-08-13
txt: ./txt/cord-003427-0dddrh4e.txt
cache: ./cache/cord-003427-0dddrh4e.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332339/
doi: 10.3390/molecules200814638
summary:
  title: Synthesis, Characterization, and Anti-Cancer Activity of Some New N′-(2-Oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazones Derivatives The cyto-toxicity and in vitro anti-cancer evaluation of the prepared compounds have been assessed against two different human tumour cell lines including human liver (HepG2) and leukaemia (Jurkat), as well as in normal cell lines derived from human embryonic kidney (HEK293) using MTT assay. As a continuation to our previously reported data [49] [50] [51] , herein we designed eight isatin hydrazide-hydrazone derivatives, considering some of the factors responsible for such activity, including (i) the presence of isatin moiety; (ii) the presence of the hydrazide-hydrazone functionality; and (iii) valproic acid moiety ( Figure 1 ). All the prepared compounds were assessed against two different human tumour cell lines, including human liver (HepG2) and leukaemia (Jurkat), as well as in normal cell lines derived from human embryonic kidney (HEK293) using MTT assay. The presence of the valproic acid moiety as hydrazide-hydrazone derivatives 4a make the compound more targeted towards Jurakt cells in vitro.

title:
  Synthesis, Characterization, and Anti-Cancer Activity of Some New N′-(2-Oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazones Derivatives

abstract:
  Eight novel N′-(2-oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazone derivatives 4a–h were synthesized and fully characterized by IR, NMR ((1)H-NMR and (13)C-NMR), elemental analysis, and X-ray crystallography. The cyto-toxicity and in vitro anti-cancer evaluation of the prepared compounds have been assessed against two different human tumour cell lines including human liver (HepG2) and leukaemia (Jurkat), as well as in normal cell lines derived from human embryonic kidney (HEK293) using MTT assay. The compounds 3e, 3f, 4a, 4c, and 4e revealed promising anti-cancer activities in tested human tumour cells lines (IC(50) values between 3 and 7 μM) as compared to the known anti-cancer drug 5-Fluorouracil (IC(50) 32–50 μM). Among the tested compounds, 4a showed specificity against leukaemia (Jurkat) cells, with an IC(50) value of 3.14 μM, but this compound was inactive in liver cancer and normal cell lines.


id: cord-003539-tazd6dvm
author: Yang, Kun
date: 2019-03-02
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429262/
doi: 10.3390/molecules24050884
title:
  Design and Synthesis of Novel Anti-Proliferative Emodin Derivatives and Studies on their Cell Cycle Arrest, Apoptosis Pathway and Migration

abstract:
  Emodin is a cell arrest and apoptosis-inducing compound that is widely distributed in different plants (rhubarb, aloe), lichens and terrestrial fungi, and also isolated from marine-derived fungi and marine sponge-associated fungi. In this study, we designed and synthesized a novel series of emodin derivatives by binding emodin to an amino acid using linkers of varying lengths and composition, and evaluated their anti-proliferative activities using HepG2 cells (human hepatic carcinoma), MCF-7 cells (human breast cancer) and human normal liver L02 cells. Most of these derivatives showed moderate to potent anti-proliferative activities. Notably, compound 7a exhibited potent anti-proliferative activity against HepG2 cells with the half maximal inhibitory concentration (IC(50)) value of 4.95 µM, which was enhanced 8.8-fold compared to the parent compound emodin (IC(50) = 43.87 µM), and it also exhibited better selective anti-proliferative activity and specificity than emodin. Moreover, further experiments demonstrated that compound 7a displayed a significant efficacy of inducing apoptosis through mitochondrial pathway via release of cytochrome c from mitochondria and subsequent activation of caspase-9 and caspase-3, inducing cell arrest at G0/G1 phase, as well as suppression of cell migration of tumor cells. The preliminary results suggested that compound 7a could be a promising lead compound for the discovery of novel anti-tumor drugs and has the potential for further investigations as an anti-cancer drug.


id: cord-003990-15rg623y
title: Synthetic, Structural, and Anticancer Activity Evaluation Studies on Novel Pyrazolylnucleosides
author: Yadav, Yogesh
date: 2019-10-30
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864788/
doi: 10.3390/molecules24213922
abstract:
  The synthesis of novel pyrazolylnucleosides 3a–e, 4a–e, 5a–e, and 6a–e are described. The structures of the regioisomers were elucidated by using extensive NMR studies. The pyrazolylnucleosides 5a–e and 6a–e were screened for anticancer activities on sixty human tumor cell lines. The compound 6e showed good activity against 39 cancer cell lines. In particular, it showed significant inhibition against the lung cancer cell line Hop-92 (GI(50) 9.3 µM) and breast cancer cell line HS 578T (GI(50) 3.0 µM).


id: cord-011969-bvun86eh
title: Hybrid Quinoline-Sulfonamide Complexes (M(2+)) Derivatives with Antimicrobial Activity
author: Diaconu, Dumitrela
date: 2020-06-26
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356327/
doi: 10.3390/molecules25122946
abstract:
  Two new series of hybrid quinoline-sulfonamide complexes (M(2+): Zn(2+), Cu(2+), Co(2+) and Cd(2+)) derivatives (QSC) were designed, synthesized and tested for their antimicrobial activity. The synthesis is straightforward and efficient, involving two steps: acylation of aminoquinoline followed by complexation with metal acetate (Cu(2+), Co(2+) and Cd(2+)) or chloride (Zn(2+)). The synthesized QSC compounds were characterized by FTIR and NMR spectroscopy and by X-ray diffraction on single crystal. The QSC compounds were preliminary screened for their antibacterial and antifungal activity and the obtained results are very promising. In this respect, the hybrid N-(quinolin-8-yl)-4-chloro-benzenesulfonamide cadmium (II), considered as leading structure for further studies, has an excellent antibacterial activity against Staphylococcus aureus ATCC25923 (with a diameters of inhibition zones of 21 mm and a minimum inhibitory concentration (MIC) of 19.04 × 10(−5) mg/mL), a very good antibacterial activity against Escherichia coli ATCC25922 (with a diameters of inhibition zones of 19 mm and a MIC of 609 × 10(−5) mg/mL), and again an excellent antifungal activity against Candida albicans ATCC10231 (with a diameters of inhibition zones of 25 mm and a MIC of 19.04 × 10(−5) mg/mL).


id: cord-012391-53hgrs40
title: Anti-Acne Action of Peptides Isolated from Burdock Root—Preliminary Studies and Pilot Testing
author: Miazga-Karska, Malgorzata
date: 2020-04-27
txt: ./txt/cord-012391-53hgrs40.txt
cache: ./cache/cord-012391-53hgrs40.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248785/
doi: 10.3390/molecules25092027
summary:
  The fraction of 46 Br-p peptides isolated from burdock root with a molecular weight below 5000 Da and theoretic pI (isoelectric point) of 3.67–11.83 showed a narrow spectrum of activity against Gram-positive acne bacterial strains. To sum up: preliminary biological studies confirmed the anti-acne properties of the isolated peptide fraction from burdock root and pointed to the possibility of using it to create an active dressing on the skin. The burdock roots samples, isolated using ultrasound and salting out procedure, were fractionated using a Sephadex G-50 gel filtration (Materials and Methods, Section 4.1.) The obtained fractions were evaluated for the amount of protein and antibacterial properties (the diffusion test in solid medium). Br-f was initially tested for antibacterial activity (Figure 1, Table 1 ), and the remaining Br-f part was further ultrafiltrated in Amicon (10 kDa cut-off), followed by freeze-drying to obtain final Br-p peptide samples (the protein content was 51 µg/mL).

abstract:
  This work aimed to study the anti-bacterial, anti-biofilm and anti-oxidant potential effects of low molecular weight (LMW) peptides (Br-p) isolated from burdock (Arctium lappa L.) roots. We conducted a preliminary study to exclude or confirm the antibiotic activity of the LMW peptides fraction of this plant. Br-p were isolated using gel filtration and a 10 kDa cut-off membrane. The obtained peptides were identified by MALDI TOF/TOF. Antibacterial activity was tested against acne strains using diffusion tests, MIC and MBC. The fibroblast cytotoxicity of Br-p was tested, and the selectivity index (SI) value was determined. The fraction of 46 Br-p peptides isolated from burdock root with a molecular weight below 5000 Da and theoretic pI (isoelectric point) of 3.67–11.83 showed a narrow spectrum of activity against Gram-positive acne bacterial strains. One of the Br-p peptides assessed on MALDI RapidDeNovo was LRCDYGRFFASKSLYDPLKKRR cationic peptide. It was analogous to that contained in A. lappa protein, and theoretically it was matched as a peptide with antibiotic nature. Br-p did not show toxicity to fibroblasts in the tested concentration up to 10 mg/mL, obtaining CC(50) 10 mg/mL. The SI value for the tested Propionibacterium strains ranged from 160 to 320. Finally, an active dressing based on chitosan/alginate/genipin was prepared using freeze-drying. The formed dressing was evaluated for its anti-acne activity. To sum up: preliminary biological studies confirmed the anti-acne properties of the isolated peptide fraction from burdock root and pointed to the possibility of using it to create an active dressing on the skin.


id: cord-012419-tmcm4kxn
author: Nakamura, Shingo
date: 2020-06-30
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412244/
doi: 10.3390/molecules25133001
title:
  Concentrated Bioshell Calcium Oxide (BiSCaO) Water Kills Pathogenic Microbes: Characterization and Activity

abstract:
  Bioshell calcium oxide (BiSCaO) exhibits deodorizing properties and broad microbicidal activity. In this study, we examined possible utility of BiSCaO Water for that purpose. BiSCaO Water was prepared by adding 10 wt% BiSCaO to clean water and gently collecting the supernatant in a bottle. The same volume of clean water was gently poured onto the BiSCaO precipitate and the supernatant was gently collected in a bottle; this process was repeated fifty times. The produced BiSCaO Water contained nanoparticles (about 400–800 nm) composed of smaller nanoparticles (100–200 nm), and was colorless and transparent, with a pH > 12.7. In vitro assays demonstrated that BiSCaO Water eliminated more than 99.9% of influenza A (H1N1) and Feline calicivirus, Escherichia coli such as NBRC 3972 and O-157:H7, Pseudomonas aeruginosa, Salmonella, and Staphylococcus aureus within 15 min. We compared BiSCaO Water with the other microbicidal reagents such as ethanol, BiSCaO, BiSCa(OH)(2) suspensions, povidone iodine, NaClO, BiSCaO dispersion and colloidal dispersion with respect to deodorization activity and microbicidal efficacy. The results showed that BiSCaO Water was a potent reagent with excellent deodorization and disinfection activities against pathogenic bacteria and viruses (including both enveloped and nonenveloped viruses).


id: cord-013364-pq9obtrc
title: Selective Targeting of αvβ5 Integrin in HepG2 Cell Line by RGDechi15D Peptide
author: Capasso, Domenica
date: 2020-09-19
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570809/
doi: 10.3390/molecules25184298
abstract:
  Recently, the research community has become increasingly concerned with the receptor αvβ5, a member of the well-known integrin family. Different ongoing studies have evidenced that αvβ5 integrin regulates not only physiological processes but also a wide array of pathological events, suggesting the receptor as a valuable biomarker to specifically target for therapeutic/diagnostic purposes. Remarkably, in some tumors the involvement of the receptor in cell proliferation, tumor dissemination and angiogenesis is well-documented. In this scenario, the availability of a selective αvβ5 antagonist without ‘off-target’ protein effects may improve survival rate in patients with highly aggressive tumors, such as hepatocellular carcinoma. We recently reported a cyclic peptide, RGDechi15D, obtained by structure-activity studies. To our knowledge it represents the first peptide-based molecule reported in the literature able to specifically bind αvβ5 integrin and not cross react with αvβ3. Here we demonstrated the ability of the peptide to diminish both adhesion and invasion of HepG2 cells, an in vitro model system for hepatocellular carcinoma, to reduce the cell proliferation through an apoptotic process, and to interfere with the PI3K pathway. The peptide, also decreases the formation of new vessels in endothelial cells. Taken together these results indicate that the peptide can be considered a promising molecule with properties suited to be assessed in the future for its validation as a selective therapeutic/diagnostic weapon in hepatocarcinoma.


id: cord-013366-sbdtpsz6
author: Ramírez-Pérez, Sergio
date: 2020-09-21
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570868/
doi: 10.3390/molecules25184322
title:
  Downregulation of Inflammatory Cytokine Release from IL-1β and LPS-Stimulated PBMC Orchestrated by ST2825, a MyD88 Dimerisation Inhibitor

abstract:
  The inflammatory process implicates homeostasis disruption and increased production of inflammatory mediators. Myeloid differentiation primary response 88 (MyD88) is an essential protein recruited after lipopolysaccharide (LPS) and interleukin (IL)-1β stimulation, a process that converges in nuclear factor kappa B (NF-κB) activation, as well as a transcription of several genes of both pro- and anti-inflammatory cytokines. The inhibition of MyD88 has shown efficacy by decrease inflammatory response, and has demonstrated potential application as a therapeutic target in chronic diseases. In this study, we investigate the effect of MyD88 dimerisation inhibitor ST2825 on cytokine production from rhIL-1β and LPS-stimulated peripheral blood mononuclear cells (PBMC) from healthy blood donors (HBD). ST2825 significantly downregulates the production of IFN-γ, IL-6, IL-12, IL-2, IL-15, IL-7, VEGF, IL-1Ra, IL-4, IL-5, IL-13 and IL-9 (p < 0.05) in LPS-stimulated PBMC. Moreover, ST2825 had a relatively low impact on IL-1β signalling pathway inhibition, showing that only a few specific cytokines, such as IFN-γ and IL-1Ra, are inhibited in rhIL-1β-stimulated PBMC (p < 0.01). In conclusion, MyD88 dimerisation inhibitor ST2825 showed high efficacy by inhibiting pro- and anti-inflammatory cytokine production in LPS-stimulated PBMC. Moreover, although rhIL-1β induced a sustained cytokine production (p < 0.05), ST2825 did not show a significant effect in the secretion of neither pro- nor anti-inflammatory cytokines in rhIL-1β-stimulated PBMC.


id: cord-013412-gj443yei
title: The Application of Porphyrins and Their Analogues for Inactivation of Viruses
author: Lebedeva, Natalya Sh.
date: 2020-09-23
txt: ./txt/cord-013412-gj443yei.txt
cache: ./cache/cord-013412-gj443yei.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583985/
doi: 10.3390/molecules25194368
summary:
  The purpose of this review paper is to summarize the main approaches developed to date in the chemical and photodynamic inactivation of human and animal viruses using porphyrins and their analogues and to analyze and discuss the information on viral targets and antiviral activity of porphyrins, chlorins, of their conjugates with organic/inorganic compounds obtained in the last 10–15 years in order to identify the most promising areas. A cationic substituent is necessary to increase the solubility of porphyrins and their analogues in aqueous media, and three nitro groups provide linking of the gp120 protein with the glycoprotein ( Figure 3 ) and thereby inhibit fusion between the virus and the cell membrane. A cationic substituent is necessary to increase the solubility of porphyrins and their analogues in aqueous media, and three nitro groups provide linking of the gp120 protein with the glycoprotein ( Figure 3 ) and thereby inhibit fusion between the virus and the cell membrane.

abstract:
  The problem of treating viral infections is extremely relevant due to both the emergence of new viral diseases and to the low effectiveness of existing approaches to the treatment of known viral infections. This review focuses on the application of porphyrin, chlorin, and phthalocyanine series for combating viral infections by chemical and photochemical inactivation methods. The purpose of this review paper is to summarize the main approaches developed to date in the chemical and photodynamic inactivation of human and animal viruses using porphyrins and their analogues and to analyze and discuss the information on viral targets and antiviral activity of porphyrins, chlorins, of their conjugates with organic/inorganic compounds obtained in the last 10–15 years in order to identify the most promising areas.


id: cord-034363-6uscua0y
author: Cerda-Cavieres, Christopher
date: 2020-10-10
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594025/
doi: 10.3390/molecules25204614
title:
  Synthesis, Docking, 3-D-Qsar, and Biological Assays of Novel Indole Derivatives Targeting Serotonin Transporter, Dopamine D2 Receptor, and Mao-A Enzyme: In the Pursuit for Potential Multitarget Directed Ligands

abstract:
  A series of 27 compounds of general structure 2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-{4-[3-(1H-3indolyl)-propyl]-1-piperazinyl}-ethanamides, Series I: 7(a–o) and (2-{4-[3-(1H-3-indolyl)-propyl]-1-piperazinyl}-acetylamine)-N-(2-morfolin-4-yl-ethyl)-fluorinated benzamides Series II: 13(a–l) were synthesized and evaluated as novel multitarget ligands towards dopamine D(2) receptor, serotonin transporter (SERT), and monoamine oxidase-A (MAO-A) directed to the management of major depressive disorder (MDD). All the assayed compounds showed affinity for SERT in the nanomolar range, with five of them displaying Ki values from 5 to 10 nM. Compounds 7k, Ki = 5.63 ± 0.82 nM, and 13c, Ki = 6.85 ± 0.19 nM, showed the highest potencies. The affinities for D(2) ranged from micro to nanomolar, while MAO-A inhibition was more discrete. Nevertheless, compounds 7m and 7n showed affinities for the D(2) receptor in the nanomolar range (7n: Ki = 307 ± 6 nM and 7m: Ki = 593 ± 62 nM). Compound 7n was the only derivative displaying comparable affinities for SERT and D(2) receptor (D(2)/SERT ratio = 3.6) and could be considered as a multitarget lead for further optimization. In addition, docking studies aimed to rationalize the molecular interactions and binding modes of the designed compounds in the most relevant protein targets were carried out. Furthermore, in order to obtain information on the structure–activity relationship of the synthesized series, a 3-D-QSAR CoMFA and CoMSIA study was conducted and validated internally and externally (q(2) = 0.625, 0.523 for CoMFA and CoMSIA and r(2)(ncv) = 0.967, 0.959 for CoMFA and CoMSIA, respectively).


id: cord-253616-7jyui5ca
title: Harringtonine Inhibits Zika Virus Infection through Multiple Mechanisms
author: Lai, Zheng-Zong
date: 2020-09-07
url: https://www.ncbi.nlm.nih.gov/pubmed/32906689/
doi: 10.3390/molecules25184082
abstract:
  Mosquito-borne Zika virus (ZIKV) is a Flavivirus that came under intense study from 2014 to 2016 for its well-known ability to cause congenital microcephaly in fetuses and neurological Guillain–Barré disease in adults. Substantial research on screening antiviral agents against ZIKV and preventing ZIKV infection are globally underway, but Food and Drug Administration (FDA)-approved treatments are not available yet. Compounds from Chinese medicinal herbs may offer an opportunity for potential therapies for anti-ZIKV infection. In this study, we evaluated the antiviral efficacy of harringtonine against ZIKV. Harringtonine possessed anti-ZIKV properties against the binding, entry, replication, and release stage through the virus life cycle. In addition, harringtonine have strong virucidal effects in ZIKV and exhibited prophylaxis antiviral ability prior ZIKV infection. The antiviral activity also observed in the treatment against Japanese encephalitis reporter virus (RP9-GFP strain). Overall, this study demonstrated that harringtonine would be a favorable potential candidate for the development of anti-ZIKV infection therapies.


id: cord-254194-962vynwk
title: Silver Nanoparticles as Potential Antiviral Agents
author: Galdiero, Stefania
date: 2011-10-24
url: https://doi.org/10.3390/molecules16108894
doi: 10.3390/molecules16108894
abstract:
  Virus infections pose significant global health challenges, especially in view of the fact that the emergence of resistant viral strains and the adverse side effects associated with prolonged use continue to slow down the application of effective antiviral therapies. This makes imperative the need for the development of safe and potent alternatives to conventional antiviral drugs. In the present scenario, nanoscale materials have emerged as novel antiviral agents for the possibilities offered by their unique chemical and physical properties. Silver nanoparticles have mainly been studied for their antimicrobial potential against bacteria, but have also proven to be active against several types of viruses including human imunodeficiency virus, hepatitis B virus, herpes simplex virus, respiratory syncytial virus, and monkey pox virus. The use of metal nanoparticles provides an interesting opportunity for novel antiviral therapies. Since metals may attack a broad range of targets in the virus there is a lower possibility to develop resistance as compared to conventional antivirals. The present review focuses on the development of methods for the production of silver nanoparticles and on their use as antiviral therapeutics against pathogenic viruses.


id: cord-256838-8rzibpbl
author: Eng, Yi Shin
date: 2019-09-27
txt: ./txt/cord-256838-8rzibpbl.txt
cache: ./cache/cord-256838-8rzibpbl.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/molecules24193505
doi: 10.3390/molecules24193505
summary:
  There are still issues regarding the conflicting pharmacologic effects, pharmacokinetics, drug interactions, adverse and clinical effects of herbal medicine and TCM. Several factors may affect the molecular mechanisms and subsequent clinical effects of TCM formulas, including individual gene-based response, composition and amount of active molecules in TCM formulas, complex interactions, and appropriateness of use of TCM formulas. From the viewpoint of pathophysiology, TCM formulas used to manage airway viral infections need to have antiviral activity against such viruses listed above, and/or to induce antiviral cytokines, and/or anti-inflammatory effect, and/or to relieve symptoms commonly presented in airway infections ( Figure 1 ). To simplify the molecular mechanisms and to correlate the pharmacologic activities with their clinical effects, five formulas of A-physicians will be used as examples against airway infections: Several health benefits of herbal medicine and TCM are claimed; for example, herbs and TCM formulas, including those discussed above, are believed to have anti-oxidative activities helpful against several diseases.

title:
  Unraveling the Molecular Mechanism of Traditional Chinese Medicine: Formulas Against Acute Airway Viral Infections as Examples

abstract:
  Herbal medicine, including traditional Chinese medicine (TCM), is widely used worldwide. Herbs and TCM formulas contain numerous active molecules. Basically, they are a kind of cocktail therapy. Herb-drug, herb-food, herb-herb, herb-microbiome, and herb-disease interactions are complex. There is potential for both benefit and harm, so only after understanding more of their mechanisms and clinical effects can herbal medicine and TCM be helpful to users. Many pharmacologic studies have been performed to unravel the molecular mechanisms; however, basic and clinical studies of good validity are still not enough to translate experimental results into clinical understanding and to provide tough evidence for better use of herbal medicines. There are still issues regarding the conflicting pharmacologic effects, pharmacokinetics, drug interactions, adverse and clinical effects of herbal medicine and TCM. Understanding study validation, pharmacologic effects, drug interactions, indications and clinical effects, adverse effects and limitations, can all help clinicians in providing adequate suggestions to patients. At present, it would be better to use herbs and TCM formulas according to their traditional indications matching the disease pathophysiology and their molecular mechanisms. To unravel the molecular mechanisms and understand the benefits and harms of herbal medicine and TCM, there is still much work to be done.


id: cord-257581-trt6s1wp
title: Three New Cycloartenol Triterpenoid Saponins from the Roots of Cimicifuga simplex Wormsk
author: Kuang, Haixue
date: 2011-05-25
txt: ./txt/cord-257581-trt6s1wp.txt
cache: ./cache/cord-257581-trt6s1wp.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/21613976/
doi: 10.3390/molecules16064348
summary:
  title: Three New Cycloartenol Triterpenoid Saponins from the Roots of Cimicifuga simplex Wormsk Three new cycloartenol triterpene saponins, named shengmaxinsides A-C, have been isolated from the ethyl acetate soluble fraction of an ethanol extract of Cimicifuga simplex Wormsk roots. simplex by column chromatography afforded three new cycloartane-type triterpenoid saponins ( Figure 1 ). The 13 C-NMR spectrum (Table 1) displayed a total of thirty eight carbon signals due to the aglycon moiety, along with a sugar unit and an acetyl unit. Its molecular formula was established as C 36 In the 13 C-NMR spectrum ( Table 1 ) a total of thirty six carbon signals due to the aglycon moiety were observed, along with a sugar unit. Four new glycosides from the aerial parts of Cimicifuga simplex Wormsk Eight new glycosides from Cimicifuga simplex Wormsk Twelve new cyclolanostanol glycosides from the underground parts of Cimicifuga simplex Wormsk

abstract:
  Three new cycloartenol triterpene saponins, named shengmaxinsides A-C, have been isolated from the ethyl acetate soluble fraction of an ethanol extract of Cimicifuga simplex Wormsk roots. Their structures were established by chemical tests and detailed spectroscopic analysis as 25-O-acetyl-7,8-didehydrocimigenol-3-O-β-D-galactopyranoside (1), 7,8-didehydrocimigenol-3-O-β-D-galactopyranoside (2) and 7,8-didehydro-24S-O-acetylhydroshengmanol-3-O-β-D-galactopyranoside (3), respectively.


id: cord-259985-uysf83sh
author: Jia, Meng-Qi
date: 2017-05-17
url: https://www.ncbi.nlm.nih.gov/pubmed/28513568/
doi: 10.3390/molecules22050810
title:
  Using UPLC-MS/MS for Characterization of Active Components in Extracts of Yupingfeng and Application to a Comparative Pharmacokinetic Study in Rat Plasma after Oral Administration

abstract:
  Yupingfeng (YPF), a famous traditional Chinese medicine, which contains a large array of compounds, has been effectually used in health protection. A two-dimensional liquid chromatography ((2)D-LC) combined with quadrupole time-of-flight mass spectrometry (QTOF-MS) method was firstly established to separate and identify chemical components in YPF. A total of 33 compounds were identified, including 15 constituents (flavonoids and saponins) in Astragali radix; seven constituents (sesquiterpenoids and polysaccharide) in Atractylodis rhizoma; and 11 constituents (chromone and coumarins) in Saposhnikoviae radix. The corresponding fragmentation pathway of typical substances was investigated. Then, seven active constituents (astragaloside, calycosin, formononetin, cimicifugoside, 4-O-beta-d-glucosyl-5-O-methylvisamminol, sec-O-glucosylhamaudol, and atractylenolide II) derived from three medicinal plants were chosen to further investigate the pharmacokinetic behavior of YPF formula using ultrahigh-performance liquid chromatography with triple quadrupole mass spectrometry system. The method was sensitive, accurate and reliable. We also used the area under the plasma concentration–time curve from zero to infinity (AUC(0−∞)) as weighting factor to make an integrated pharmacokinetic curve. Results show that the constituents of Saposhnikoviae radix have the best absorption and pharmacokinetic behavior and may play important role in leading to the changes of overall therapeutic effects of YPF. Further study is needed to confirm the association between them.


id: cord-262094-b4yuh5y9
author: Shi, Yanhong
date: 2018-05-29
url: https://www.ncbi.nlm.nih.gov/pubmed/29844266/
doi: 10.3390/molecules23061305
title:
  Separation and Quantification of Four Main Chiral Glucosinolates in Radix Isatidis and Its Granules Using High-Performance Liquid Chromatography/Diode Array Detector Coupled with Circular Dichroism Detection

abstract:
  As chemical drugs, separation and quantification of the specific enantiomer from the chiral compounds in herbal medicines are becoming more important. To clarify the chemical characterization of chiral glucosinolates—the antiviral active ingredients of Radix Isatidis, an optimized efficient method of HPLC-UV-CD was developed to simultaneously separate and quantify the four main chiral glucosinolates: progoitrin, epiprogoitrin, and R,S-goitrin. The first step was to determine progoitrin, epiprogoitrin, and R,S-goitrin using HPLC-UV, and then determine the R-goitrin and S-goitrin by coupling with CD detection. Subsequently, through the linear relations between anisotropy factor (g factor) and the percent optical purity of R-goitrin, the contents of R-goitrin and S-goitrin from the R,S-goitrin mixture were calculated separately. Furthermore, the chemical composition features of the four chiral glucosinolates in 37 samples from crude drugs, decoction pieces, and granules of R. Isatidis were conducted. The total content of the four glucosinolates was obviously higher in crude drugs, and the variance character of each glucosinolate contents was different. In summary, the accurate measurement method reported here allows for better control of the internal quality of R. Isatidis and its granules and provides a powerful approach for the analysis of other chiral components in traditional Chinese medicines.


id: cord-264326-teahway7
author: Eleftheriou, Phaedra
date: 2020-05-29
txt: ./txt/cord-264326-teahway7.txt
cache: ./cache/cord-264326-teahway7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32485894/
doi: 10.3390/molecules25112529
summary:
  According to docking analysis the most promising results were found for HCV protease, DPP-4, α-thrombin and coagulation Factor Xa known inhibitors, with several of them exhibiting estimated free binding energy lower than −8.00 kcal/mol and better prediction results than reference compounds. Since the 3D structure of the active site of the enzyme is crucial for catalytic activity, we proceeded to a comparison of the SARS-CoV-2 main protease, Mpro, with the HIV-1 protease, the HCV protease (NS3 protein) and the human proteases DPP-4, thrombin, Factor Xa, renin and ACE, which constitute known drug targets with approved inhibitors. The structural similarity between the SARS-CoV-2 protease and some of the selected proteases, in combination with the existence of the same amino acids at certain positions of the substrate cleavage site, such as Ser at the P1'' position of the recognition sequence of the HCV protease and thrombin are promising features in the effort to identify effective SARS-CoV-2 protease inhibitors among the approved drugs of the selected proteases.

title:
  In Silico Evaluation of the Effectivity of Approved Protease Inhibitors against the Main Protease of the Novel SARS-CoV-2 Virus

abstract:
  The coronavirus disease, COVID-19, caused by the novel coronavirus SARS-CoV-2, which first emerged in Wuhan, China and was made known to the World in December 2019 turned into a pandemic causing more than 126,124 deaths worldwide up to April 16th, 2020. It has 79.5% sequence identity with SARS-CoV-1 and the same strategy for host cell invasion through the ACE-2 surface protein. Since the development of novel drugs is a long-lasting process, researchers look for effective substances among drugs already approved or developed for other purposes. The 3D structure of the SARS-CoV-2 main protease was compared with the 3D structures of seven proteases, which are drug targets, and docking analysis to the SARS-CoV-2 protease structure of thirty four approved and on-trial protease inhibitors was performed. Increased 3D structural similarity between the SARS-CoV-2 main protease, the HCV protease and α-thrombin was found. According to docking analysis the most promising results were found for HCV protease, DPP-4, α-thrombin and coagulation Factor Xa known inhibitors, with several of them exhibiting estimated free binding energy lower than −8.00 kcal/mol and better prediction results than reference compounds. Since some of the compounds are well-tolerated drugs, the promising in silico results may warrant further evaluation for viral anticipation. DPP-4 inhibitors with anti-viral action may be more useful for infected patients with diabetes, while anti-coagulant treatment is proposed in severe SARS-CoV-2 induced pneumonia.


id: cord-266149-h8bu3jrq
title: Hyperpolarization of Nitrile Compounds Using Signal Amplification by Reversible Exchange
author: Kim, Sarah
date: 2020-07-23
txt: ./txt/cord-266149-h8bu3jrq.txt
cache: ./cache/cord-266149-h8bu3jrq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32717970/
doi: 10.3390/molecules25153347
summary:
  Signal Amplification by Reversible Exchange (SABRE), a hyperpolarization technique, has been harnessed as a powerful tool to achieve useful hyperpolarized materials by polarization transfer from parahydrogen. By performing SABRE in various magnetic fields and concentrations on nitrile compounds, we unveiled its hyperpolarization properties to maximize the spin polarization and its transfer to the next spins. Its optimal polarization factor with different magnetic fields and concentrations also showed the same trend as the butyronitrile case-an approximately 100-fold Its optimal polarization factor with different magnetic fields and concentrations also showed the same trend as the butyronitrile case-an approximately 100-fold enhancement in 70 G with a 5 µL amount of valeronitrile. By performing SABRE with various magnetic fields and substrate concentrations, we unveiled its hyperpolarization characteristics and properties to maximize the polarization and its transfer efficiency. By performing SABRE with various magnetic fields and substrate concentrations, we unveiled its hyperpolarization characteristics and properties to maximize the polarization and its transfer efficiency.

abstract:
  Signal Amplification by Reversible Exchange (SABRE), a hyperpolarization technique, has been harnessed as a powerful tool to achieve useful hyperpolarized materials by polarization transfer from parahydrogen. In this study, we systemically applied SABRE to a series of nitrile compounds, which have been rarely investigated. By performing SABRE in various magnetic fields and concentrations on nitrile compounds, we unveiled its hyperpolarization properties to maximize the spin polarization and its transfer to the next spins. Through this sequential study, we obtained a ~130-fold enhancement for several nitrile compounds, which is the highest number ever reported for the nitrile compounds. Our study revealed that the spin polarization on hydrogens decreases with longer distances from the nitrile group, and its maximum polarization is found to be approximately 70 G with 5 μL of substrates in all structures. Interestingly, more branched structures in the ligand showed less effective polarization transfer mechanisms than the structural isomers of butyronitrile and isobutyronitrile. These first systematic SABRE studies on a series of nitrile compounds will provide new opportunities for further research on the hyperpolarization of various useful nitrile materials.


id: cord-268088-y4vg7frb
title: Current Perspectives of the Applications of Polyphenols and Flavonoids in Cancer Therapy
author: Montané, Xavier
date: 2020-07-23
txt: ./txt/cord-268088-y4vg7frb.txt
cache: ./cache/cord-268088-y4vg7frb.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/molecules25153342
doi: 10.3390/molecules25153342
summary:
  Among the natural compounds that produce beneficial effects on human health, polyphenols have shown potential therapeutic applications in cancer due to their protective functions in plants, their use as food additives, and their excellent antioxidant properties. This review shows a wide range of trials in which polyphenolic compounds play a crucial role as anticancer medicines alone or in combination with other drugs at different stages of cancer: cancer initiation, promotion, and growth or progression. In point of fact, studies demonstrated that resveratrol has in vitro effects against a large range of human tumors: breast, skin, ovary, stomach, prostate, colon, liver, pancreas, cervix, thyroid carcinoma cells, lymphoid, and myeloid cancer cells [22] . In point of fact, studies demonstrated that resveratrol has in vitro effects against a large range of human tumors: breast, skin, ovary, stomach, prostate, colon, liver, pancreas, cervix, thyroid carcinoma cells, lymphoid, and myeloid cancer cells [22] .

abstract:
  The development of anticancer therapies that involve natural drugs has undergone exponential growth in recent years. Among the natural compounds that produce beneficial effects on human health, polyphenols have shown potential therapeutic applications in cancer due to their protective functions in plants, their use as food additives, and their excellent antioxidant properties. The possibility of combining conventional drugs—which are usually more aggressive than natural compounds—with polyphenols offers very valuable advantages such as the building of more efficient anticancer therapies with less side effects on human health. This review shows a wide range of trials in which polyphenolic compounds play a crucial role as anticancer medicines alone or in combination with other drugs at different stages of cancer: cancer initiation, promotion, and growth or progression. Moreover, the future directions in applications of various polyphenols in cancer therapy are emphasized.


id: cord-268902-npug5c8p
title: The Roles of Direct Recognition by Animal Lectins in Antiviral Immunity and Viral Pathogenesis
author: Liu, Yang
date: 2015-01-29
url: https://www.ncbi.nlm.nih.gov/pubmed/25642837/
doi: 10.3390/molecules20022272
abstract:
  Lectins are a group of proteins with carbohydrate recognition activity. Lectins are categorized into many families based on their different cellular locations as well as their specificities for a variety of carbohydrate structures due to the features of their carbohydrate recognition domain (CRD) modules. Many studies have indicated that the direct recognition of particular oligosaccharides on viral components by lectins is important for interactions between hosts and viruses. Herein, we aim to globally review the roles of this recognition by animal lectins in antiviral immune responses and viral pathogenesis. The different classes of mammalian lectins can either recognize carbohydrates to activate host immunity for viral elimination or can exploit those carbohydrates as susceptibility factors to facilitate viral entry, replication or assembly. Additionally, some arthropod C-type lectins were recently identified as key susceptibility factors that directly interact with multiple viruses and then facilitate infection. Summarization of the pleiotropic roles of direct viral recognition by animal lectins will benefit our understanding of host-virus interactions and could provide insight into the role of lectins in antiviral drug and vaccine development.


id: cord-272113-j82z4q8x
author: Akaji, Kenichi
date: 2020-08-27
url: https://doi.org/10.3390/molecules25173920
doi: 10.3390/molecules25173920
title:
  Design and Evaluation of Anti-SARS-Coronavirus Agents Based on Molecular Interactions with the Viral Protease

abstract:
  Three types of new coronaviruses (CoVs) have been identified recently as the causative viruses for the severe pneumonia-like respiratory illnesses, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and corona-virus disease 2019 (COVID-19). Neither therapeutic agents nor vaccines have been developed to date, which is a major drawback in controlling the present global pandemic of COVID-19 caused by SARS coronavirus 2 (SARS-CoV-2) and has resulted in more than 20,439,814 cases and 744,385 deaths. Each of the 3C-like (3CL) proteases of the three CoVs is essential for the proliferation of the CoVs, and an inhibitor of the 3CL protease (3CL(pro)) is thought to be an ideal therapeutic agent against SARS, MERS, or COVID-19. Among these, SARS-CoV is the first corona-virus isolated and has been studied in detail since the first pandemic in 2003. This article briefly reviews a series of studies on SARS-CoV, focusing on the development of inhibitors for the SARS-CoV 3CL(pro) based on molecular interactions with the 3CL protease. Our recent approach, based on the structure-based rational design of a novel scaffold for SARS-CoV 3CL(pro) inhibitor, is also included. The achievements summarized in this short review would be useful for the design of a variety of novel inhibitors for corona-viruses, including SARS-CoV-2.


id: cord-272465-i2l4cq8h
title: New Potential Pharmacological Functions of Chinese Herbal Medicines via Regulation of Autophagy
author: Law, Betty Yuen Kwan
date: 2016-03-17
txt: ./txt/cord-272465-i2l4cq8h.txt
cache: ./cache/cord-272465-i2l4cq8h.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26999089/
doi: 10.3390/molecules21030359
summary:
  Hinders α-synuclein accumulation in neural cells and suppression of the proliferation of glioma cells through induction of autophagy [162, 163] Radix salviae miltiorrhizae (Dan shen) Moves blood, breaks up blood stasis, cools heat, cools blood Tanshinone IIA Induction of autophagic cell death of leukemia via activation of AMPK/mTOR, ERK/mTOR and p70 S6K signaling [164] Ligusticum wallichii (Chuan xiong) Moves blood, moves and regulates qi, dispels wind Ligustrazine Akebia saponin PA (AS) is one of the bioactive components found in Radix dipsaci, AS induced autophagic and apoptotic cell death of gastric cancer cells through both the AMPK/mTOR and PI3K/Akt/mTOR signaling and the downstream activation of p38/JNK molecular pathway, which facilitated capase-3-dependent apoptosis [147] . However, alisol B has been reported as a new autophagy inducer functioning through activation of CaMKK/AMPK/mTOR signaling, induction of apoptosis and triggering of cell death in breast cancer cells [156] . Gambogic acid induced oxidative stress dependent caspase activation regulates both apoptosis and autophagy by targeting various key molecules (Nf-κB, Beclin-1, p62 and NBR1) in human bladder cancer cells

abstract:
  Autophagy is a universal catabolic cellular process for quality control of cytoplasm and maintenance of cellular homeostasis upon nutrient deprivation and environmental stimulus. It involves the lysosomal degradation of cellular components such as misfolded proteins or damaged organelles. Defects in autophagy are implicated in the pathogenesis of diseases including cancers, myopathy, neurodegenerations, infections and cardiovascular diseases. In the recent decade, traditional drugs with new clinical applications are not only commonly found in Western medicines, but also highlighted in Chinese herbal medicines (CHM). For instance, pharmacological studies have revealed that active components or fractions from Chaihu (Radix bupleuri), Hu Zhang (Rhizoma polygoni cuspidati), Donglingcao (Rabdosia rubesens), Hou po (Cortex magnoliae officinalis) and Chuan xiong (Rhizoma chuanxiong) modulate cancers, neurodegeneration and cardiovascular disease via autophagy. These findings shed light on the potential new applications and formulation of CHM decoctions via regulation of autophagy. This article reviews the roles of autophagy in the pharmacological actions of CHM and discusses their new potential clinical applications in various human diseases.


id: cord-276598-tm0yj2sn
title: Opening up the Toolbox: Synthesis and Mechanisms of Phosphoramidates
author: Itumoh, Emeka J.
date: 2020-08-13
txt: ./txt/cord-276598-tm0yj2sn.txt
cache: ./cache/cord-276598-tm0yj2sn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32823507/
doi: 10.3390/molecules25163684
summary:
  For the low yielding derivatives, the reaction was more selective to three identified by-products, H-phosphonate, trialkyl phosphate, and tetraalkyl diphosphate, as well as some other unidentified Jang and coworkers reported a facile synthetic route to form P-Ns using diphenyl phosphoric acid (dPPA) and an amine in the presence of both a chlorinating agent (Cl 3 CCN) and a base (Et 3 N), which was added to sequester the acid formed during the reaction (Scheme 6c) [99] . proposed a reaction mechanism involving single-electron transfer oxidation of the copper catalyst, which favored the formation of the Cu(II)-amine complex (Scheme 27) [103] . proposed a reaction mechanism involving single-electron transfer oxidation of the copper catalyst, which favored the formation of the Cu(II)-amine complex (Scheme 27) [103] . [105] , the mechanism involves the formation of the (RO) 2 oxidized to form the Cu(III)-amine-phosphonate complex, which undergoes reductive elimination of the copper catalyst to yield the desired P-N.

abstract:
  This review covers the main synthetic routes to and the corresponding mechanisms of phosphoramidate formation. The synthetic routes can be separated into six categories: salt elimination, oxidative cross-coupling, azide, reduction, hydrophosphinylation, and phosphoramidate-aldehyde-dienophile (PAD). Examples of some important compounds synthesized through these routes are provided. As an important class of organophosphorus compounds, the applications of phosphoramidate compounds, are also briefly introduced.


id: cord-276781-ujvkcz4s
title: Synthesis of New Imidazopyridine Nucleoside Derivatives Designed as Maribavir Analogues
author: Papadakis, Georgios
date: 2020-10-03
txt: ./txt/cord-276781-ujvkcz4s.txt
cache: ./cache/cord-276781-ujvkcz4s.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/molecules25194531
doi: 10.3390/molecules25194531
summary:
  At the same time, the benzimidazole L-riboside Maribavir is about to be evaluated in Phase III trials involving transplant recipients with HCMV infections that are refractory or resistant to the currently approved drugs as well as for its potential superiority over Valganciclovir in HSCT patients. However, initial Phase III clinical trials failed to prove sufficient benefits for post-transplant At the same time, the benzimidazole l-riboside Maribavir is about to be evaluated in Phase III trials involving transplant recipients with HCMV infections that are refractory or resistant to the currently approved drugs as well as for its potential superiority over Valganciclovir in HSCT patients. The resulting oil was purified by column chromatography, using a mixture of CHCl 3 /MeOH (99/1 to 97/3, v/v) as the eluent, to afford 8a, as a mixture with its corresponding α-anomer 9a (280 mg, total yield 53% for two anomers, 8a:9a (3-β:α) ratio 12:1, as estimated by 1 [4,5-b] pyridin-2-amine (11b): These derivatives were prepared by a procedure analogous to that described for 8a,9a,10a,11a, starting from imidazopyridine 7b (280 mg, 1.14 mmol).

abstract:
  The strong inhibition of Human Cytomegalovirus (HCMV) replication by benzimidazole nucleosides, like Triciribine and Maribavir, has prompted us to expand the structure–activity relationships of the benzimidazole series, using as a central core the imidazo[4,5-b]pyridine scaffold. We have thus synthesized a number of novel amino substituted imidazopyridine nucleoside derivatives, which can be considered as 4-(or 7)-aza-d-isosters of Maribavir and have evaluated their potential antiviral activity. The target compounds were synthesized upon glycosylation of suitably substituted 2-aminoimidazopyridines, which were prepared in six steps starting from 2-amino-6-chloropyridine. Even if the new compounds possessed only a slight structural modification when compared to the original drug, they were not endowed with interesting antiviral activity. Even so, three derivatives showed promising cytotoxic potential.


id: cord-277491-q18b88lm
author: Cao, Ying-Li
date: 2011-02-11
url: https://doi.org/10.3390/molecules16021544
doi: 10.3390/molecules16021544
title:
  Identification and Characterization of Three Novel Small Interference RNAs That Effectively Down-Regulate the Isolated Nucleocapsid Gene Expression of SARS Coronavirus

abstract:
  Nucleocapsid (N) protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is a major pathological determinant in the host that may cause host cell apoptosis, upregulate the proinflammatory cytokine production, and block innate immune responses. Therefore, N gene has long been thought an ideal target for the design of small interference RNA (siRNA). siRNA is a class of small non-coding RNAs with a size of 21-25nt that functions post-transcriptionally to block targeted gene expression. In this study, we analyzed the N gene coding sequences derived from 16 different isolates, and found that nucleotide deletions and substitutions are mainly located at the first 440nt sequence. Combining previous reports and the above sequence information, we create three novel siRNAs that specifically target the conserved and unexploited regions in the N gene. We show that these siRNAs could effectively and specifically block the isolated N gene expression in mammal cells. Furthermore, we provide evidence to show that N gene can effectively up-regulate M gene mediated interferon β (IFNβ) production, while blocking N gene expression by specific siRNA significantly reduces IFNβ gene expression. Our data indicate that the inhibitory effect of siRNA on the isolated N gene expression might be influenced by the sequence context around the targeted sites.


id: cord-279281-gh298gaa
author: Zannou, Oscar
date: 2020-08-14
txt: ./txt/cord-279281-gh298gaa.txt
cache: ./cache/cord-279281-gh298gaa.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32824080/
doi: 10.3390/molecules25163715
summary:
  A natural hydrophilic DES constituted of sodium acetate (hydrogen bond acceptor) and formic acid (hydrogen bond donor) designed to evaluate the total phenolic compound (TPC), total flavonoid (TFC), total anthocyanin (TACN), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and ferric reducing antioxidant power (FRAP) values of Roselle. Nonetheless, C-H stretching weakened upon addition of water and disappeared completely in SAFAm. In the present study, sodium acetate:formic acid (1:2 molar ratio) was employed as a natural DES and coded as SAFA0 to extract polyphenolic compounds, especially anthocyanins and to evaluate the antioxidant activity of Roselle calyces. The reduced second-order models in terms of actual factors for the responses such as TPC, TFC, TACN, FRAP and DPPH radical scavenging values of Roselle calyces as a function of molarity ratio (X 1 ), additional water (X 2 ) and solvent to solid ratio (X 3 ) were obtained as follows: These equations showed up the response patterns for individual measurement and intricacy of sceneries.

title:
  Recovery and Stabilization of Anthocyanins and Phenolic Antioxidants of Roselle (Hibiscus sabdariffa L.) with Hydrophilic Deep Eutectic Solvents

abstract:
  Deep eutectic solvents (DESs) have got huge interest as new green and sustainable solvents for the extraction of bioactive compounds from plants in recent decades. In the present study, we aimed to investigate the effectiveness of hydrophilic DES for the extraction of anthocyanin and polyphenol antioxidants from Roselle. A natural hydrophilic DES constituted of sodium acetate (hydrogen bond acceptor) and formic acid (hydrogen bond donor) designed to evaluate the total phenolic compound (TPC), total flavonoid (TFC), total anthocyanin (TACN), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and ferric reducing antioxidant power (FRAP) values of Roselle. Distilled water, 70% ethanol, and 80% methanol used as conventional solvents for comparison. The results indicated that the DES prepared in molarity ratio (SAFA(m)) was the most efficient. Subsequently, this prominent DES selected for the optimization and the optimum extraction conditions were 1:3.6 molarity ratio, 0% additional water, and 10 mL solvent. TPC, TFC, TACN, FRAP, and DPPH radical scavenging at the optimum point were 233.26 mg GAE/g, 10.14 mg ECE/g, 10.62 mg D3S/g, 493.45 mmol ISE/g, and 343.41 mmol TE/g, respectively. The stability tests showed that anthocyanins were more stable in SAFA(m). These findings revealed that SAFA(m) is an effective green solvent for the extraction of polyphenols from various plants.


id: cord-280292-90i45kjk
author: Daescu, Monica
date: 2020-10-07
txt: ./txt/cord-280292-90i45kjk.txt
cache: ./cache/cord-280292-90i45kjk.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33036335/
doi: 10.3390/molecules25194571
summary:
  The chemical interaction of AC with the NaOH solutions, having the concentration ranging between 0.001 and 0.3 M, induces a gradual enhancement of the photoluminescence excitation (PLE) and PL spectra, when the exposure time of samples at the UV light increases until 140 min, as a result of the formation of p-aminophenol and sodium acetate. According to Figure 2b -e, after 140 min of exposure to UV light, the AC interacted with the NaOH solutions having the concentrations equal to 10 −3 , 10 −2 , 10 −1 and 0.3 M, the intensity of the PL spectra is equal to 6.09 × 10 5 , 3.1 × 10 5 , 7.5 × 10 4 and 2.3 × 10 4 counts/sec, respectively. The interaction of the aqueous solution of Paracetamol with NaOH leads to a shift of the PLE band from 323 nm (Figure 3a ) to 337 nm (Figure 3c ), the subsequent exposure at UV light for 140 min inducing an intensity increase of the PLE band from 2.98 × 10 6 to 1.74 × 10 7 counts/sec.

title:
  Photoluminescence as a Valuable Tool in the Optical Characterization of Acetaminophen and the Monitoring of Its Photodegradation Reactions

abstract:
  In this work, new evidence for the photodegradation reactions of acetaminophen (AC) is reported by photoluminescence (PL), Raman scattering and FTIR spectroscopy. Under excitation wavelength of 320 nm, AC shows a PL band in the spectral range of 340–550 nm, whose intensity decreases by exposure to UV light. The chemical interaction of AC with the NaOH solutions, having the concentration ranging between 0.001 and 0.3 M, induces a gradual enhancement of the photoluminescence excitation (PLE) and PL spectra, when the exposure time of samples at the UV light increases until 140 min, as a result of the formation of p-aminophenol and sodium acetate. This behavior is not influenced by the excipients or other active compounds in pharmaceutical products as demonstrated by PLE and PL studies. Experimental arguments for the obtaining of p-aminophenol and sodium acetate, when AC has interacted with NaOH, are shown by Raman scattering and FTIR spectroscopy.


id: cord-280807-0g1uo0rd
author: Tomani, Jean Claude Didelot
date: 2020-10-14
txt: ./txt/cord-280807-0g1uo0rd.txt
cache: ./cache/cord-280807-0g1uo0rd.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33066442/
doi: 10.3390/molecules25204693
summary:
  noldeae, as well as caffeic acid, isoquercetin, and ER2.4 and ER2.7 fractions revealed significant inhibitory effects on Caspase-1 activities, and on IL-1β and IL-6 production. noldeae, as well as caffeic acid, isoquercetin, and ER2.4 and ER2.7 fractions revealed the highest inhibitory effects on Caspase-1 activities, and on IL-1β and IL-6 production. Therefore, we investigated the effect of our compounds and fractions of interest on inflammasome activation-induced cell death by measuring the release of lactate dehydrogenase (LDH) in the culture Concentrations of 20 µM YVAD and 20 µg/mL Dex were used as controls. Therefore, we investigated the effect of our compounds and fractions of interest on inflammasome activation-induced cell death by measuring the release of lactate dehydrogenase (LDH) in the culture supernatants. Before investigating the anti-inflammatory activity of different fractions, their effect on the cell viability (THP-1, monocytes and derived-macrophages, and RAW264.7) was screened as previously reported [21] .

title:
  The Inhibition of NLRP3 Inflammasome and IL-6 Production by Hibiscus noldeae Baker f. Derived Constituents Provides a Link to Its Anti-Inflammatory Therapeutic Potentials

abstract:
  The activation of NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome and/or its components is associated with the physio-pathogenesis of many respiratory diseases including asthma, COPD (chronic obstructive pulmonary disease), SARS Cov-2 (severe acute respiratory syndrome coronavirus 2), and in several autoimmune diseases. Hibiscus noldeae Baker f. has been widely reported to be traditionally used in the treatment of different ailments, some of which are of inflammatory background such as asthma, wounds, headache, etc. However, the claims have not been supported by evidence at the molecular and functional levels. Here, we report on the bio-guided fractionation of H. noldeae and assessment of the inhibitory properties of some fractions and purified compounds on NLRP3 inflammasome and Interleukin 6 (IL-6). The activation of the NLRP3 inflammasome was determined by detecting the activity of caspase-1 and the production of Interleukin 1β (IL-1β) in Lipopolysaccharide (LPS) and ATP-stimulated Tamm-Horsfall Protein 1 (THP-1) macrophages, while the production of IL-6 was studied in LPS-stimulated RAW264.7 mouse macrophages. It was observed that hexane and ethyl acetate fractions of the crude extract of the aerial parts of H. noldeae, as well as caffeic acid, isoquercetin, and ER2.4 and ER2.7 fractions revealed significant inhibitory effects on Caspase-1 activities, and on IL-1β and IL-6 production. The ER2.4 and ER2.7 fractions downregulated the production of IL-1β and IL-6, in a similar range as the caspase-1 inhibitor AC-YVAD-CHO and the drug Dexamethasone, both used as controls, respectively. Overall, our work does provide the very first scientific based evidence for Hibiscus noldeae anti-inflammatory effects and widespread use by traditional healers in Rwanda for a variety of ailments.


id: cord-281281-knelqmzx
author: Villas-Boas, Gustavo R.
date: 2020-09-07
txt: ./txt/cord-281281-knelqmzx.txt
cache: ./cache/cord-281281-knelqmzx.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32906733/
doi: 10.3390/molecules25184086
summary:
  The use of bioinformatics and other computational tools in addition to molecular modeling has helped researchers from different areas in the search for strategies for diagnosing viral infection, in the development of vaccines for its prevention, as well as in the discovery of new anti-SARS-CoV-2 agents. In the context of COVID-19, this characteristic was important for a better understanding of the origin of SARS-CoV-2 from the comparative analysis of genomic data of the new virus with others from the same family, suggesting its origin from natural selection, with modifications in its spike protein, more specifically in the host receptor binding domain, which may have enhanced its interaction and recognition by the human cell [83, 91] . The contributions of bioinformatics and molecular modeling in elucidating essential targets for the planning and development of new drugs, and the analysis of already known compounds, support the search for safer and more effective treatments against SARS-CoV-2 infection.

title:
  The New Coronavirus (SARS-CoV-2): A Comprehensive Review on Immunity and the Application of Bioinformatics and Molecular Modeling to the Discovery of Potential Anti-SARS-CoV-2 Agents

abstract:
  On March 11, 2020, the World Health Organization (WHO) officially declared the outbreak caused by the new coronavirus (SARS-CoV-2) a pandemic. The rapid spread of the disease surprised the scientific and medical community. Based on the latest reports, news, and scientific articles published, there is no doubt that the coronavirus has overloaded health systems globally. Practical actions against the recent emergence and rapid expansion of the SARS-CoV-2 require the development and use of tools for discovering new molecular anti-SARS-CoV-2 targets. Thus, this review presents bioinformatics and molecular modeling strategies that aim to assist in the discovery of potential anti-SARS-CoV-2 agents. Besides, we reviewed the relationship between SARS-CoV-2 and innate immunity, since understanding the structures involved in this infection can contribute to the development of new therapeutic targets. Bioinformatics is a technology that assists researchers in coping with diseases by investigating genetic sequencing and seeking structural models of potential molecular targets present in SARS-CoV2. The details provided in this review provide future points of consideration in the field of virology and medical sciences that will contribute to clarifying potential therapeutic targets for anti-SARS-CoV-2 and for understanding the molecular mechanisms responsible for the pathogenesis and virulence of SARS-CoV-2.


id: cord-281668-960trqex
title: A Review of Small Molecule Inhibitors and Functional Probes of Human Cathepsin L
author: Dana, Dibyendu
date: 2020-02-06
txt: ./txt/cord-281668-960trqex.txt
cache: ./cache/cord-281668-960trqex.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32041276/
doi: 10.3390/molecules25030698
summary:
  These inhibitors further provided the option of varying the leaving group that targets S2â�² site; more hydrophobic substituents were preferred at this position as comparison of ki/Ki values of the inactivation exhibited the following trend for Aa: Gly < Ala < Val < Leu < Phe < 4-NO2-Ph. The nitrophenyl analog (Entry 7, Table 2 ) which incur both hydrophobicity and electron-withdrawing property exerted the maximum potency and selectivity for cathepsin L over other tested cysteine proteases. These inhibitors further provided the option of varying the leaving group that targets S2â�² site; more hydrophobic substituents were preferred at this position as comparison of ki/Ki values of the inactivation exhibited the following trend for Aa: Gly < Ala < Val < Leu < Phe < 4-NO2-Ph. The nitrophenyl analog (Entry 7, Table 2 ) which incur both hydrophobicity and electron-withdrawing property exerted the maximum potency and selectivity for cathepsin L over other tested cysteine proteases.

abstract:
  Human cathepsin L belongs to the cathepsin family of proteolytic enzymes with primarily an endopeptidase activity. Although its primary functions were originally thought to be only of a housekeeping enzyme that degraded intracellular and endocytosed proteins in lysosome, numerous recent studies suggest that it plays many critical and specific roles in diverse cellular settings. Not surprisingly, the dysregulated function of cathepsin L has manifested itself in several human diseases, making it an attractive target for drug development. Unfortunately, several redundant and isoform-specific functions have recently emerged, adding complexities to the drug discovery process. To address this, a series of chemical biology tools have been developed that helped define cathepsin L biology with exquisite precision in specific cellular contexts. This review elaborates on the recently developed small molecule inhibitors and probes of human cathepsin L, outlining their mechanisms of action, and describing their potential utilities in dissecting unknown function.


id: cord-283127-jetmocvk
author: Wang, Denong
date: 2015-03-12
url: https://www.ncbi.nlm.nih.gov/pubmed/25774492/
doi: 10.3390/molecules20034610
title:
  Targeting N-Glycan Cryptic Sugar Moieties for Broad-Spectrum Virus Neutralization: Progress in Identifying Conserved Molecular Targets in Viruses of Distinct Phylogenetic Origins

abstract:
  Identifying molecular targets for eliciting broadly virus-neutralizing antibodies is one of the key steps toward development of vaccines against emerging viral pathogens. Owing to genomic and somatic diversities among viral species, identifying protein targets for broad-spectrum virus neutralization is highly challenging even for the same virus, such as HIV-1. However, viruses rely on host glycosylation machineries to synthesize and express glycans and, thereby, may display common carbohydrate moieties. Thus, exploring glycan-binding profiles of broad-spectrum virus-neutralizing agents may provide key information to uncover the carbohydrate-based virus-neutralizing epitopes. In this study, we characterized two broadly HIV-neutralizing agents, human monoclonal antibody 2G12 and Galanthus nivalis lectin (GNA), for their viral targeting activities. Although these agents were known to be specific for oligomannosyl antigens, they differ strikingly in virus-binding activities. The former is HIV-1 specific; the latter is broadly reactive and is able to neutralize viruses of distinct phylogenetic origins, such as HIV-1, severe acute respiratory syndrome coronavirus (SARS-CoV), and human cytomegalovirus (HCMV). In carbohydrate microarray analyses, we explored the molecular basis underlying the striking differences in the spectrum of anti-virus activities of the two probes. Unlike 2G12, which is strictly specific for the high-density Man(9)GlcNAc(2)Asn (Man9)-clusters, GNA recognizes a number of N-glycan cryptic sugar moieties. These include not only the known oligomannosyl antigens but also previously unrecognized tri-antennary or multi-valent GlcNAc-terminating N-glycan epitopes (Tri/m-Gn). These findings highlight the potential of N-glycan cryptic sugar moieties as conserved targets for broad-spectrum virus neutralization and suggest the GNA-model of glycan-binding warrants focused investigation.


id: cord-284113-qboon2uv
author: Zheljazkov, Valtcho D.
date: 2020-10-12
txt: ./txt/cord-284113-qboon2uv.txt
cache: ./cache/cord-284113-qboon2uv.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33053634/
doi: 10.3390/molecules25204631
summary:
  The hypothesis was that wild hemp would have a different EO content, composition, and antimicrobial activity compared with the EOs of registered industrial hemp cultivars, new hemp breeding lines, and a hemp strain (unregistered cultivar) that is currently used for the commercial production of CBD. Overall, the EOs of the wild hemps and registered cultivars in this study were similar to those reported previously: 0.23 to 0.31% in fresh inflorescences [14] , 0.29 to 0.19% depending on the collection time with higher EO yield from plants sampled earlier (in September than in October) [13] , and 0.1% in stems and 0.15% in the leaves of wild hemp from Austria [15] , respectively. Overall, the results from this study suggest that wild/spontaneous hemp in Europe is chemotaxonomically related to the industrial hemp varieties (cultivars) grown in Europe and deviate from the chemical profile of the USA hemp strain that was developed from marijuana-type cannabis for the commercial production of CBD.

title:
  Industrial, CBD, and Wild Hemp: How Different Are Their Essential Oil Profile and Antimicrobial Activity?

abstract:
  Hemp (Cannabis sativa L.) is currently one of the most controversial and promising crops. This study compared nine wild hemp (C. sativa spp. spontanea V.) accessions with 13 registered cultivars, eight breeding lines, and one cannabidiol (CBD) hemp strain belonging to C. sativa L. The first three groups had similar main essential oil (EO) constituents, but in different concentrations; the CBD hemp had a different EO profile. The concentration of the four major constituents in the industrial hemp lines and wild hemp accessions varied as follows: β-caryophyllene 11–22% and 15.4–29.6%; α-humulene 4.4–7.6% and 5.3–11.9%; caryophyllene oxide 8.6–13.7% and 0.2–31.2%; and humulene epoxide 2, 2.3–5.6% and 1.2–9.5%, respectively. The concentration of CBD in the EO of wild hemp varied from 6.9 to 52.4% of the total oil while CBD in the EO of the registered cultivars varied from 7.1 to 25%; CBD in the EO of the breeding lines and in the CBD strain varied from 6.4 to 25% and 7.4 to 8.8%, respectively. The concentrations of δ9-tetrahydrocannabinol (THC) in the EO of the three groups of hemp were significantly different, with the highest concentration being 3.5%. The EO of wild hemp had greater antimicrobial activity compared with the EO of registered cultivars. This is the first report to show that significant amounts of CBD could be accumulated in the EO of wild and registered cultivars of hemp following hydro-distillation. The amount of CBD in the EO can be greater than that in the EO of the USA strain used for commercial production of CBD. Furthermore, this is among the first reports that show greater antimicrobial activity of the EO of wild hemp vs. the EO of registered cultivars. The results suggest that wild hemp may offer an excellent opportunity for future breeding and the selection of cultivars with a desirable composition of the EO and possibly CBD-rich EO production.


id: cord-286655-5vorrnq3
author: Vivek-Ananth, R.P.
date: 2020-08-22
txt: ./txt/cord-286655-5vorrnq3.txt
cache: ./cache/cord-286655-5vorrnq3.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32842606/
doi: 10.3390/molecules25173822
summary:
  Lastly, we filtered the subset of phytochemicals whose binding energy in the best docked pose with TMPRSS2 (respectively, cathepsin L) is ≤−8.5 kcal/mol (respectively, ≤−8.0 In the third stage, we performed protein-ligand docking using AutoDock Vina [34] . Finally, in the fifth stage, for the top three inhibitors of TMPRSS2 namely, T1 (qingdainone), T2 (edgeworoside C) and T3 (adlumidine), and of cathepsin L namely, C1 (ararobinol), C2 ((+)-oxoturkiyenine) and C3 (3α,17α-cinchophylline), their respective protein-ligand complexes were analyzed using 180 ns MD simulation (Section 3; Figures 8 and 9; Supplementary Figures S1 and S2) and their interaction binding energy was computed using MM-PBSA method (Section 3; Table 3 ). As mentioned above, we have identified 96 potential natural product inhibitors of TMPRSS2 by computational screening of 14,011 phytochemicals produced by Indian medicinal plants, and these 96 compounds labelled T1-T96 are listed in Supplementary Table S1 along with their PubChem identifier, common name, IUPAC name and structure in SMILES format.

title:
  In Silico Identification of Potential Natural Product Inhibitors of Human Proteases Key to SARS-CoV-2 Infection

abstract:
  Presently, there are no approved drugs or vaccines to treat COVID-19, which has spread to over 200 countries and at the time of writing was responsible for over 650,000 deaths worldwide. Recent studies have shown that two human proteases, TMPRSS2 and cathepsin L, play a key role in host cell entry of SARS-CoV-2. Importantly, inhibitors of these proteases were shown to block SARS-CoV-2 infection. Here, we perform virtual screening of 14,011 phytochemicals produced by Indian medicinal plants to identify natural product inhibitors of TMPRSS2 and cathepsin L. AutoDock Vina was used to perform molecular docking of phytochemicals against TMPRSS2 and cathepsin L. Potential phytochemical inhibitors were filtered by comparing their docked binding energies with those of known inhibitors of TMPRSS2 and cathepsin L. Further, the ligand binding site residues and non-covalent interactions between protein and ligand were used as an additional filter to identify phytochemical inhibitors that either bind to or form interactions with residues important for the specificity of the target proteases. This led to the identification of 96 inhibitors of TMPRSS2 and 9 inhibitors of cathepsin L among phytochemicals of Indian medicinal plants. Further, we have performed molecular dynamics (MD) simulations to analyze the stability of the protein-ligand complexes for the three top inhibitors of TMPRSS2 namely, qingdainone, edgeworoside C and adlumidine, and of cathepsin L namely, ararobinol, (+)-oxoturkiyenine and 3α,17α-cinchophylline. Interestingly, several herbal sources of identified phytochemical inhibitors have antiviral or anti-inflammatory use in traditional medicine. Further in vitro and in vivo testing is needed before clinical trials of the promising phytochemical inhibitors identified here.


id: cord-287123-ldkuwcc7
title: The Formyl Peptide Receptors: Diversity of Ligands and Mechanism for Recognition
author: He, Hui-Qiong
date: 2017-03-13
txt: ./txt/cord-287123-ldkuwcc7.txt
cache: ./cache/cord-287123-ldkuwcc7.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/molecules22030455
doi: 10.3390/molecules22030455
summary:
  The formyl peptide receptors (FPRs) are G protein-coupled receptors that transduce chemotactic signals in phagocytes and mediate host-defense as well as inflammatory responses including cell adhesion, directed migration, granule release and superoxide production. N-formylated peptides constitute the most commonly studied class of FPR agonists that trigger a variety of biological activities in myeloid cells, such as chemokinesis, chemotaxis, calcium flux, cytokine production and superoxide anion generation. Through binding with the high affinity receptor FPR1, fMLF and other N-formylated peptides serve as potent chemoattractants, which also include activated complements (C5a, C3a) and chemokines, in recruiting and guiding leukocytes to the site of bacterial infection and to damaged tissues. As the first identified endogenous peptide agonist for FPR [56] , documented studies have shown that it exerts pro-inflammatory activities through FPR2 in phagocytes, epithelial cells and T lymphocytes, including stimulating production of inflammatory mediators and enhancing the expression of cytokine receptors [109] [110] [111] [112] [113] .

abstract:
  The formyl peptide receptors (FPRs) are G protein-coupled receptors that transduce chemotactic signals in phagocytes and mediate host-defense as well as inflammatory responses including cell adhesion, directed migration, granule release and superoxide production. In recent years, the cellular distribution and biological functions of FPRs have expanded to include additional roles in homeostasis of organ functions and modulation of inflammation. In a prototype, FPRs recognize peptides containing N-formylated methionine such as those produced in bacteria and mitochondria, thereby serving as pattern recognition receptors. The repertoire of FPR ligands, however, has expanded rapidly to include not only N-formyl peptides from microbes but also non-formyl peptides of microbial and host origins, synthetic small molecules and an eicosanoid. How these chemically diverse ligands are recognized by the three human FPRs (FPR1, FPR2 and FPR3) and their murine equivalents is largely unclear. In the absence of crystal structures for the FPRs, site-directed mutagenesis, computer-aided ligand docking and structural simulation have led to the identification of amino acids within FPR1 and FPR2 that interact with several formyl peptides. This review article summarizes the progress made in the understanding of FPR ligand diversity as well as ligand recognition mechanisms used by these receptors.


id: cord-287754-dh6abx2t
title: Lectins with Anti-HIV Activity: A Review
author: Akkouh, Ouafae
date: 2015-01-06
txt: ./txt/cord-287754-dh6abx2t.txt
cache: ./cache/cord-287754-dh6abx2t.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/molecules20010648
doi: 10.3390/molecules20010648
summary:
  Examples of lectins that exhibit antiviral activity and bind high-mannose carbohydrates are jacalin [25] , concanavalin A [26] , Urtica diocia agglutinin [27] , Myrianthus holstii lectin, P. The mannose-specific plant lectins Hippeastrum hybrid agglutinin, Galanthus nivalis agglutinin, Narcissus pseudonarcissus agglutinin; Cymbidium agglutinin; cyanovirin-N; and N-acetylglucosamine specific Urtica dioica agglutinin efficiently abrogate dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)-directed HIV-1 capture and subsequent transmission to T lymphocytes [55] . The nematode (Laxus oneistus) Ca 2+ -dependent C-type lectin Mermaid, a structural homologue of DC-SIGN devoid of cytotoxicity, shares the glycan specificity with DC-SIGN, interacts with high mannose structures on gp120 and prevents HIV-1 binding to DC-SIGN on DCs. Mermaid inhibits DC-SIGN-mediated HIV-1 transmission from DC to T cells. Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: Potential applications to microbicide development The high mannose-type glycan binding lectin actinohivin: Dimerization greatly improves anti-HIV activity

abstract:
  Lectins including flowering plant lectins, algal lectins, cyanobacterial lectins, actinomycete lectin, worm lectins, and the nonpeptidic lectin mimics pradimicins and benanomicins, exhibit anti-HIV activity. The anti-HIV plant lectins include Artocarpus heterophyllus (jacalin) lectin, concanavalin A, Galanthus nivalis (snowdrop) agglutinin-related lectins, Musa acuminata (banana) lectin, Myrianthus holstii lectin, Narcissus pseudonarcissus lectin, and Urtica diocia agglutinin. The anti-HIV algal lectins comprise Boodlea coacta lectin, Griffithsin, Oscillatoria agardhii agglutinin. The anti-HIV cyanobacterial lectins are cyanovirin-N, scytovirin, Microcystis viridis lectin, and microvirin. Actinohivin is an anti-HIV actinomycete lectin. The anti-HIV worm lectins include Chaetopterus variopedatus polychaete marine worm lectin, Serpula vermicularis sea worm lectin, and C-type lectin Mermaid from nematode (Laxus oneistus). The anti-HIV nonpeptidic lectin mimics comprise pradimicins and benanomicins. Their anti-HIV mechanisms are discussed.


id: cord-289288-46nyje11
title: Novel Isoxazolidine and γ-Lactam Analogues of Homonucleosides
author: Piotrowska, Dorota G.
date: 2019-11-06
txt: ./txt/cord-289288-46nyje11.txt
cache: ./cache/cord-289288-46nyje11.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31698778/
doi: 10.3390/molecules24224014
summary:
  Homonucleoside analogues cis-16 and trans-17 having a (5-methoxycarbonyl)isoxazolidine framework were synthesized via the 1,3-dipolar cycloaddition of nucleobase-derived nitrones with methyl acrylate. The synthetic strategy for γ-lactam homonucleosides 15 relies on the 1,3-dipolar cycloaddition of nucleobase-derived nitrones 13 with methyl acrylate, followed by the hydrogenolysis of the N-O bond in an isoxazolidine scaffold, which was accompanied by the intramolecular cyclization to transform cycloadducts 14 into compounds 15 (Scheme 1). The synthetic strategy for γ-lactam homonucleosides 15 relies on the 1,3-dipolar cycloaddition of nucleobase-derived nitrones 13 with methyl acrylate, followed by the hydrogenolysis of the N-O bond in an isoxazolidine scaffold, which was accompanied by the intramolecular cyclization to transform cycloadducts 14 into compounds 15 (Scheme 1). A series of isoxazolidine analogues of homonucleosides cis-14 and trans-14 was synthesized by 1,3-dipolar cycloaddition of nucleobase-derived nitrones 13 and methyl acrylate.

abstract:
  Homonucleoside analogues cis-16 and trans-17 having a (5-methoxycarbonyl)isoxazolidine framework were synthesized via the 1,3-dipolar cycloaddition of nucleobase-derived nitrones with methyl acrylate. Hydrogenolysis of the isoxazolidines containing thymine, dihydrouracil, theophylline and adenine moieties efficiently led to the formation of the respective γ-lactam analogues. γ-Lactam analogues having 5-bromouracil and 5-chlorouracil fragments were synthesized by treatment of uracil-containing γ-lactams with NBS and NCS. Isoxazolidine and γ-lactam analogues of homonucleosides obtained herein were evaluated for activity against a broad range of DNA and RNA viruses. None of the compounds that were tested exhibited antiviral or cytotoxic activity at concentrations up to 100 µM. The cytostatic activities of all compounds toward nine cancerous cell lines was tested. γ-Lactams trans-15e (Cl-Ura) and cis-15h (Theo) appeared the most active toward pancreatic adenocarcinoma cells (Capan-1), showing IC(50) values 21.5 and 18.2 µM, respectively. Isoxazolidine cis-15e (Cl-Ura) inhibited the proliferation of colorectal carcinoma (HCT-116).


id: cord-290855-6umgvt28
title: Antiviral Effects of Plant-Derived Essential Oils and Their Components: An Updated Review
author: Ma, Li
date: 2020-06-05
txt: ./txt/cord-290855-6umgvt28.txt
cache: ./cache/cord-290855-6umgvt28.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32516954/
doi: 10.3390/molecules25112627
summary:
  Previous studies have demonstrated essential oils to be excellent candidates to treat antiviral-resistant infection associated with their chemical complexity which confers broad-spectrum mechanisms of action and non-specific antiviral properties. This review provides an up-to-date overview of the antiviral efficacy of essential oils from a wide range of plant species and their characteristic components, as well as their overall mechanisms of action, focusing on the last decade. Virucidal effects of EOs extracted from numerous aromatic and herbal plants are also well documented on a variety of viruses, such as IFV, HSV, HIV, yellow fever virus, and avian influenza, etc. Essential oils from Star Anise, Australian tea tree, oregano, Eucalyptus caesia, to name a few, have been demonstrated to exhibit high anti-HSV-1 activities in vitro (Table 1 ).

abstract:
  The presence of resistance to available antivirals calls for the development of novel therapeutic agents. Plant-derived essential oils may serve as alternative sources of virus-induced disease therapy. Previous studies have demonstrated essential oils to be excellent candidates to treat antiviral-resistant infection associated with their chemical complexity which confers broad-spectrum mechanisms of action and non-specific antiviral properties. However, almost no comprehensive reviews are updated to generalize knowledge in this regard and disclose the interplay between the components and their antiviral activities. This review provides an up-to-date overview of the antiviral efficacy of essential oils from a wide range of plant species and their characteristic components, as well as their overall mechanisms of action, focusing on the last decade. The roles of individual components relative to the overall antiviral efficacy of essential oils, together with the antiviral activity of essential oils in comparison with commercial drugs are also discussed. Lastly, the inadequacies in current research and future research are put forward. This review will provide references in the design of new drug prototypes and improve our understanding of the proper applications of essential oils in the future.


id: cord-291180-xurmzmwj
title: A Review on Applications of Computational Methods in Drug Screening and Design
author: Lin, Xiaoqian
date: 2020-03-18
txt: ./txt/cord-291180-xurmzmwj.txt
cache: ./cache/cord-291180-xurmzmwj.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/molecules25061375
doi: 10.3390/molecules25061375
summary:
  Then, virtual screening methods (e.g., molecular docking, pharmacophore modeling, and QSAR) as well as structureand ligand-based classical/de novo drug design were introduced and discussed. On the other hand, ligand-based drug design can also use quantitative structure-activity relationships (QSAR) [50, 51] in which a correlation between calculated properties of molecules and their experimentally determined biological activity is derived, to predict the activity of new analogs. With the assembly of reasonable molecular fragments, the objective of drug design method is to produce a certain novel molecule that display highest biological activity, absorption, metabolism, elimination (ADME) and lowest toxicity properties at different environments, which belong to the application range of QSAR models. With the booming era of "big" data, machine learning methods have developed into deep learning approaches, which are a more efficient way for drug designers to deal with important biological properties from large amount of compound databases.

abstract:
  Drug development is one of the most significant processes in the pharmaceutical industry. Various computational methods have dramatically reduced the time and cost of drug discovery. In this review, we firstly discussed roles of multiscale biomolecular simulations in identifying drug binding sites on the target macromolecule and elucidating drug action mechanisms. Then, virtual screening methods (e.g., molecular docking, pharmacophore modeling, and QSAR) as well as structure- and ligand-based classical/de novo drug design were introduced and discussed. Last, we explored the development of machine learning methods and their applications in aforementioned computational methods to speed up the drug discovery process. Also, several application examples of combining various methods was discussed. A combination of different methods to jointly solve the tough problem at different scales and dimensions will be an inevitable trend in drug screening and design.


id: cord-295171-vx4cypf7
title: In Vitro and in Vivo Antiviral Activity of Mizoribine Against Foot-And-Mouth Disease Virus
author: Li, Shi-Fang
date: 2019-05-03
url: https://doi.org/10.3390/molecules24091723
doi: 10.3390/molecules24091723
abstract:
  Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals, which has significant economic consequences in affected countries. As the currently available vaccines against FMD provide no protection until 4–7 days post-vaccination, the only alternative method to control the spread of FMD virus (FMDV) during outbreaks is the application of antiviral agents. Hence, it is important to identify effective antiviral agents against FMDV infection. In this study, we found that mizoribine has potent antiviral activity against FMDV replication in IBRS-2 cells. A time-of-drug-addition assay demonstrated that mizoribine functions at the early stage of replication. Moreover, mizoribine also showed antiviral effect on FMDV in vivo. In summary, these results revealed that mizoribine could be a potential antiviral drug against FMDV.


id: cord-295229-dxl7wvcx
author: Liu, Kelly Y. P.
date: 2013-02-25
txt: ./txt/cord-295229-dxl7wvcx.txt
cache: ./cache/cord-295229-dxl7wvcx.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/molecules18032483
doi: 10.3390/molecules18032483
summary:
  The aim of this study was to elucidate the potential anti-inflammatory and anti-allergic activities of PHF, Moutan Cortex (Danpi/DP) and gallic acid (GA) using human basophils (KU812 cells), which are crucial effector cells in allergic inflammation. The aim of the present study was to elucidate the mechanisms of the in vitro anti-inflammatory and anti-allergic activities of PHF, Danpi and GA via their modulation of: (i) expression of cell surface adhesion molecules and (ii) the release of chemokines and cytokines from allergy-related alarmin IL-33-activated human basophils, which are crucial effector cells of allergic inflammation in allergic asthma and AD [27] . . Suppressive effect of inflammatory cytokine IL-6 release from IL-33-activated human basophilic KU812 cells treated with PHF (100, 500 and 1,000 μg/mL), DP (100, 500 and 1,000 μg/mL) or GA (10 and 100 μg/mL) for 18 h.

title:
  Anti-Inflammatory and Anti-Allergic Activities of Pentaherb Formula, Moutan Cortex (Danpi) and Gallic Acid

abstract:
  Pentaherb formula (PHF) has been proven to improve the quality of life of children with atopic dermatitis without side effects. The aim of this study was to elucidate the potential anti-inflammatory and anti-allergic activities of PHF, Moutan Cortex (Danpi/DP) and gallic acid (GA) using human basophils (KU812 cells), which are crucial effector cells in allergic inflammation. PHF, DP and GA could significantly suppress the expression of allergic inflammatory cytokine IL-33-upregulated intercellular adhesion molecule (ICAM)-1, and the release of chemokines CCL2, CCL5, CXCL8 and inflammatory cytokine IL-6 from KU812 cells (all p < 0.05). With the combined use of dexamethasone (0.01 μg/mL) and GA (10 μg/mL), the suppression of ICAM-1 expression and CCL5 and IL-6 release of IL-33-activated KU812 cells were significantly greater than the use of GA alone (all p < 0.05). The suppression of the IL-33-induced activation of intracellular signalling molecules p38 mitogen activated protein kinase, nuclear factor-κB and c-Jun amino-terminal kinase in GA-treated KU812 cells could be the underlying mechanism for the suppression on ICAM-1, chemokines and cytokines. The combined use of dexamethasone with the natural products PHF or DP or GA might therefore enhance the development of a novel therapeutic modality for allergic inflammatory diseases with high potency and fewer side effects.


id: cord-299985-9954q0zg
author: Illesca, Paola
date: 2020-09-27
url: https://www.ncbi.nlm.nih.gov/pubmed/32992508/
doi: 10.3390/molecules25194433
title:
  Protective Effects of Eicosapentaenoic Acid Plus Hydroxytyrosol Supplementation Against White Adipose Tissue Abnormalities in Mice Fed a High-Fat Diet

abstract:
  Objective: Obesity induced by high-fat diet (HFD) elicits white adipose tissue dysfunction. In this study, we have hypothesized that the metabolic modulator eicosapentaenoic acid (EPA) combined with the antioxidant hydroxytyrosol (HT) attenuates HFD-induced white adipose tissue (WAT) alterations. Methods: C57BL/6J mice were administered with a HFD (60% fat, 20% protein, 20% carbohydrates) or control diet (CD; 10% fat, 20% protein, 70% carbohydrates), with or without EPA (50 mg/kg/day), HT (5 mg/kg/day), or both for 12 weeks. Determinations in WAT include morphological parameters, EPA and docosahexaenoic acid content in phospholipids (gas chromatography), lipogenesis, oxidative stress (OS) and inflammation markers, and gene expression and activities of transcription factors, such as sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-gamma (PPAR-γ), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (p65 subunit) and nuclear factor erythroid 2-related factor 2 (Nrf2) (quantitative polymerase chain reaction and enzyme linked immunosorbent assay). Results: HFD led to WAT hypertrophy in relation to PPAR-γ downregulation. WAT metabolic dysfunction was characterized by upregulation of lipogenic SREBP-1c system, mitochondrial energy metabolism depression, loss of the antioxidant Nrf2 signaling with OS enhancement, n-3 long-chain polyunsaturated fatty acids depletion and activation of the pro-inflammatory NF-κB system. EPA and HT co-supplementation diminished HFD-dependent effects additively, reaching values close or similar to controls. Conclusion: Data presented strengthen the importance of combined protocols such as EPA plus HT to attenuate metabolic-inflammatory states triggered by obesity.


id: cord-300872-blycbi4u
title: Recent Advances in the Synthesis and Biological Activity of 8-Hydroxyquinolines
author: Saadeh, Haythem A.
date: 2020-09-21
txt: ./txt/cord-300872-blycbi4u.txt
cache: ./cache/cord-300872-blycbi4u.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/molecules25184321
doi: 10.3390/molecules25184321
summary:
  Some of these strains have even become resistant to many antibiotics and chemotherapeutic agents; These prepared compounds were subjected to bioactivity screening against the highly pathogenic H5N1 avian influenza viruses, with the results expressed as percentages of growth inhibition, and to cytotoxicity evaluation against the A549 cell line. A synthetic procedure (Scheme 13) involved a condensation reaction between the amino group (NH2) in 49 and the carbonyl group in salicylic aldehyde (50), followed by intramolecular cyclization under a These prepared compounds were screened for potential anticancer activity against MCF-7, HCT 116, HepG-2, and A549 using the MMT assay. This compound was screened against MCF-7 and Hela cancer cell lines using MMT assay, giving IC50 values of 21.02 and 27.73 mM, respectively In addition, Shamsi and coworkers prepared 16 quinoline-based 1,3,4-oxadiazole-triazole derivatives (Scheme 14) based on the hybrid strategy of nitrogen-containing heterocyclic scaffolds [36] .

abstract:
  Compounds containing the 8-hydroxyquinoline (8-HQ) 1 nucleus exhibit a wide range of biological activities, including antimicrobial, anticancer, and antifungal effects. The chemistry and biology of this group have attracted the attention of chemists, medicinal chemists, and professionals in health sciences. A number of prescribed drugs incorporate this group, and numerous 8-HQ- based molecules can be used to develop potent lead compounds with good efficacy and low toxicity. This review focusses on the recent advances in the synthesis of 8-HQ derivatives with different pharmacological properties, including anticancer, antiviral, and antibacterial activities. For this purpose, recent relevant references were searched in different known databases and search engines, such as MEDLINE (PubMed), Google Scholar, Science Direct, Scopus, Cochrane, Scientific Information Database (SID), SciFinder, and Institute for Scientific Information (ISI) Web of Knowledge. This review article provides a literature overview of the various synthetic strategies and biological activities of 8-HQ derivatives and covers the recent related literature. Taken together, compounds containing the 8-HQ moiety have huge therapeutic value and can act as potential building blocks for various pharmacologically active scaffolds. In addition, several described compounds in this review could act leads for the development of drugs against numerous diseases including cancer.


id: cord-302190-co4tju7u
author: Yu, Sheng
date: 2017-02-16
txt: ./txt/cord-302190-co4tju7u.txt
cache: ./cache/cord-302190-co4tju7u.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/molecules22020299
doi: 10.3390/molecules22020299
summary:
  As a ubiquitous biflavonoid, amentoflavone has been found with a large number of pharmacological functions, such as anti-inflammation, anti-oxidation, anti-tumor, anti-senescence, anti-virus, anti-diabetes, neuroprotective activities, and effects on cardiovascular system and central nervous system. In another study, it was found that the naturally-occurring biflavonoid could prevent scopolamine-induced memory impairment, inhibit AChE and enhance antioxidant enzyme activity in mice, which exhibited its protection against memory deficits [176] . From the contents above, we could conclude that amentoflavone is a bioactive biflavonoid with a variety of pharmacological effects, which has been derived from many natural plants. Taken together, since amentoflavone is a promising and naturally-occurring biflavonoid with so many bioactivities, its systematic druggability research as a candidate drug is obviously necessary, including its preparation study (extraction and isolation from plants, chemical synthesis, or biological synthesis), structural modification study, Absorption-Distribution-Metabolism-Excretion (ADME) study in normal animals and animal models, acute and chronic toxicological studies.

title:
  A Review on the Phytochemistry, Pharmacology, and Pharmacokinetics of Amentoflavone, a Naturally-Occurring Biflavonoid

abstract:
  Amentoflavone (C(30)H(18)O(10)) is a well-known biflavonoid occurring in many natural plants. This polyphenolic compound has been discovered to have some important bioactivities, including anti-inflammation, anti-oxidation, anti-diabetes, and anti-senescence effects on many important reactions in the cardiovascular and central nervous system, etc. Over 120 plants have been found to contain this bioactive component, such as Selaginellaceae, Cupressaceae, Euphorbiaceae, Podocarpaceae, and Calophyllaceae plant families. This review paper aims to profile amentoflavone on its plant sources, natural derivatives, pharmacology, and pharmacokinetics, and to highlight some existing issues and perspectives in the future.


id: cord-306633-69ljgkqy
author: Završnik, Davorka
date: 2011-07-19
txt: ./txt/cord-306633-69ljgkqy.txt
cache: ./cache/cord-306633-69ljgkqy.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/molecules16076023
doi: 10.3390/molecules16076023
summary:
  title: Benzylidene-bis-(4-Hydroxycoumarin) and Benzopyrano-Coumarin Derivatives: Synthesis, (1)H/(13)C-NMR Conformational and X-ray Crystal Structure Studies and In Vitro Antiviral Activity Evaluations We report on the synthesis of 4-hydroxycoumarin dimers 1–15 bearing an aryl substituent on the central linker and fused benzopyranocoumarin derivatives 16–20 and on their in vitro broad anti-DNA and RNA virus activity evaluations. The X-ray crystal structure analysis revealed that two 4-hydroxycoumarin moieties in the 4-trifluoromethylphenyland 2-nitrophenyl derivatives (compounds 7 and 9, respectively) are intramolecularly hydrogen-bonded between hydroxyl and carbonyl oxygen atoms. The 4-hydroxycoumarin moieties are intramolecularly hydrogen bonded between hydroxyl and carbonyl oxygen atoms in both structures (see Figures 4a and 4b and Table S1 in ESI), thus forming two eight-membered rings. X-ray crystal structure analysis of 4-trifluoromethylphenyl-and 2-nitrophenyl derivatives 7 and 9 revealed intramolecular hydrogen bonding between hydroxyl and carbonyl oxygen atoms of two 4-hydroxycoumarin moieties resulting in the formation of two eight-membered rings.

title:
  Benzylidene-bis-(4-Hydroxycoumarin) and Benzopyrano-Coumarin Derivatives: Synthesis, (1)H/(13)C-NMR Conformational and X-ray Crystal Structure Studies and In Vitro Antiviral Activity Evaluations

abstract:
  We report on the synthesis of 4-hydroxycoumarin dimers 1–15 bearing an aryl substituent on the central linker and fused benzopyranocoumarin derivatives 16–20 and on their in vitro broad anti-DNA and RNA virus activity evaluations. The chemical identities and structure of compounds 1–20 were deduced from their homo- and heteronuclear NMR measurements whereas the conformational properties of 5, 14 and 20 were assessed by the use of 1D difference NOE enhancements. Unequivocal proof of the stereostructure of compounds 7, 9, 16 and 18 was obtained by single crystal X-ray diffraction method. The X-ray crystal structure analysis revealed that two 4-hydroxycoumarin moieties in the 4-trifluoromethylphenyl- and 2-nitrophenyl derivatives (compounds 7 and 9, respectively) are intramolecularly hydrogen-bonded between hydroxyl and carbonyl oxygen atoms. Consequently, the compounds 7 and 9 adopt conformations in which two 4-hydroxy-coumarin moieties are anti-disposed. Antiviral activity evaluation results indicated that the 4-bromobenzylidene derivative of bis-(4-hydroxycoumarin) (compound 3) possesses inhibitory activity against HSV-1 (KOS), HSV-2 (G), vaccinia virus and HSV-1 TK(-) KOS (ACV(r)) at a concentration of 9–12 μM and at a minimum cytotoxic concentration (MCC) greater than 20 μM. Compounds 4–6, 8, and 20 were active against feline herpes virus (50% effective concentration, EC(50) = 5–8.1 μM), that is at a 4-7-fold lower concentration than the MCC.


id: cord-307731-a2fqmaly
author: Vázquez, Javier
date: 2020-10-15
txt: ./txt/cord-307731-a2fqmaly.txt
cache: ./cache/cord-307731-a2fqmaly.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/molecules25204723
doi: 10.3390/molecules25204723
summary:
  In particular, the compounds obtained in the final rank order lead to meaningful increases in both performance and robustness over the single-modality approaches, but the results also demonstrate the sensitivity of the performance to the target structural details (i.e., the nature of the template ligand in measurements of molecular similarity and the reference protein pocket in docking studies) [67, 68] . In particular, the compounds obtained in the final rank order lead to meaningful increases in both performance and robustness over the single-modality approaches, but the results also demonstrate the sensitivity of the performance to the target structural details (i.e., the nature of the template ligand in measurements of molecular similarity and the reference protein pocket in docking studies) [67, 68] .

title:
  Merging Ligand-Based and Structure-Based Methods in Drug Discovery: An Overview of Combined Virtual Screening Approaches

abstract:
  Virtual screening (VS) is an outstanding cornerstone in the drug discovery pipeline. A variety of computational approaches, which are generally classified as ligand-based (LB) and structure-based (SB) techniques, exploit key structural and physicochemical properties of ligands and targets to enable the screening of virtual libraries in the search of active compounds. Though LB and SB methods have found widespread application in the discovery of novel drug-like candidates, their complementary natures have stimulated continued efforts toward the development of hybrid strategies that combine LB and SB techniques, integrating them in a holistic computational framework that exploits the available information of both ligand and target to enhance the success of drug discovery projects. In this review, we analyze the main strategies and concepts that have emerged in the last years for defining hybrid LB + SB computational schemes in VS studies. Particularly, attention is focused on the combination of molecular similarity and docking, illustrating them with selected applications taken from the literature.


id: cord-309722-04pp3lv0
title: Delivery of RNAi Therapeutics to the Airways—From Bench to Bedside
author: Qiu, Yingshan
date: 2016-09-20
txt: ./txt/cord-309722-04pp3lv0.txt
cache: ./cache/cord-309722-04pp3lv0.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27657028/
doi: 10.3390/molecules21091249
summary:
  Notes: AHR, airway hyperresponsiveness; ALI, Acute lung injury; BALF, bronchoalveolar lavage fluid; CD86, cluster of differentiation 86; C-kit, a stem cell factor receptor; DCs, dendritic cells; HMGB1A, high mobility group box-1 A peptide; IFU, infectious unit; LPS, lipopolysaccharide; Mpl, myeloproliferative leukemia virus oncogene; OVA, ovalbumin; R3V6, an arginine-rich peptide; Rip2, receptor-interacting protein 2; RSV, respiratory syncytial virus; S1Plyase, sphingosine-1-phosphate lyase, SOCS, Suppressors of cytokine signaling protein 3; STAT6, signal transducer and activator of transcription factor 6; Syk, spleen tyrosine kinase; Tf-PEI, transferrin polyethylenimine; T h 2, T helper 2 cells; TNF-α, tumor necrosis factor-α; VEGFR, Vascular endothelial growth factor. After siRNA targeting, SOCS3 was intranasally administered to the lungs of chronic asthmatic mouse model [12] , the silencing of SOCS3 down-regulated the expression of T h 2 cell associated cytokines, IL-4, IL-5 and IL-13, leading to substantial reduction of airway inflammation, AHR as well as IgE production.

abstract:
  RNA interference (RNAi) is a potent and specific post-transcriptional gene silencing process. Since its discovery, tremendous efforts have been made to translate RNAi technology into therapeutic applications for the treatment of different human diseases including respiratory diseases, by manipulating the expression of disease-associated gene(s). Similar to other nucleic acid-based therapeutics, the major hurdle of RNAi therapy is delivery. Pulmonary delivery is a promising approach of delivering RNAi therapeutics directly to the airways for treating local conditions and minimizing systemic side effects. It is a non-invasive route of administration that is generally well accepted by patients. However, pulmonary drug delivery is a challenge as the lungs pose a series of anatomical, physiological and immunological barriers to drug delivery. Understanding these barriers is essential for the development an effective RNA delivery system. In this review, the different barriers to pulmonary drug delivery are introduced. The potential of RNAi molecules as new class of therapeutics, and the latest preclinical and clinical studies of using RNAi therapeutics in different respiratory conditions are discussed in details. We hope this review can provide some useful insights for moving inhaled RNAi therapeutics from bench to bedside.


id: cord-310268-8q4tk6fd
title: DNA Aptamers in the Diagnosis and Treatment of Human Diseases
author: Zhu, Qinchang
date: 2015-11-25
txt: ./txt/cord-310268-8q4tk6fd.txt
cache: ./cache/cord-310268-8q4tk6fd.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26610462/
doi: 10.3390/molecules201219739
summary:
  Nucleic acid aptamers are RNA and single-stranded (ss) DNA oligonucleotides with lengths typically ranging from 15 to 70 mers, which have the same level of target-binding affinity as monoclonal antibodies (the dissociation constant (K d ) usually ranges from 0.1 to 50 nM) [5, 6] . This SELEX is able to generate DNA aptamers that recognize the cell-surface or intracellular target protein in their native conformation, which shows great potential in cell-specific therapeutics and diagnostic applications [26] [27] [28] . Recently, modified cell-SELEX methods have been developed to select aptamers targeting specific cells like disease state cells and metastatic cells. In the era of personalized medicine, DNA aptamer-based therapeutics and diagnostics are believed to have great potential for extensive application because of their flexibility to specifically bind to any molecule targets.

abstract:
  Aptamers have a promising role in the field of life science and have been extensively researched for application as analytical tools, therapeutic agents and as vehicles for targeted drug delivery. Compared with RNA aptamers, DNA aptamers have inherent advantages in stability and facility of generation and synthesis. To better understand the specific potential of DNA aptamers, an overview of the progress in the generation and application of DNA aptamers in human disease diagnosis and therapy are presented in this review. Special attention is given to researches that are relatively close to practical application. DNA aptamers are expected to have great potential in the diagnosis and treatment of human diseases.


id: cord-313668-zz32fpvz
author: Tian, Yong-Qi
date: 2015-12-26
txt: ./txt/cord-313668-zz32fpvz.txt
cache: ./cache/cord-313668-zz32fpvz.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/26712735/
doi: 10.3390/molecules21010034
summary:
  title: Asteltoxins with Antiviral Activities from the Marine Sponge-Derived Fungus Aspergillus sp. Two new asteltoxins named asteltoxin E (2) and F (3), and a new chromone (4), together with four known compounds were isolated from a marine sponge–derived fungus, Aspergillus sp. Marine sponge-derived fungus tends to produce structurally unique and biologically active natural products which have been documented in recent years; however, only a handful of reports have described new metabolites which have antiviral activities [7, 8] . The fungal strain SCSIO XWS02F40 was isolated from the sponge Callyspongia sp., which was collected from the sea area near Xuwen County, Guangdong Province, China, during August 2013. The fungal strain SCSIO XWS02F40 was isolated from the sponge Callyspongia sp., which was collected from the sea area near Xuwen County, Guangdong Province, China, during August 2013. In conclusion, three new compounds, Asteltoxin E (2), Asteltoxin F (3) and 7-hydroxy-2-(2-hydroxypropyl)-5-pentyl chromone (4), together with four known compounds were isolated from a marine sponge-derived fungus, Aspergillus sp.

title:
  Asteltoxins with Antiviral Activities from the Marine Sponge-Derived Fungus Aspergillus sp. SCSIO XWS02F40

abstract:
  Two new asteltoxins named asteltoxin E (2) and F (3), and a new chromone (4), together with four known compounds were isolated from a marine sponge–derived fungus, Aspergillus sp. SCSIO XWS02F40. The structures of the compounds (1–7) were determined by the extensive 1D- and 2D-NMR spectra, and HRESIMS spectrometry. All the compounds were tested for their antiviral (H1N1 and H3N2) activity. Compounds 2 and 3 showed significant activity against H3N2 with the prominent IC(50) values of 6.2 ± 0.08 and 8.9 ± 0.3 μM, respectively. In addition, compound 2 also exhibited inhibitory activity against H1N1 with an IC(50) value of 3.5 ± 1.3 μM.


id: cord-316474-407bthqj
title: Bioinformatics Resources and Tools for Phage Display
author: Huang, Jian
date: 2011-01-18
txt: ./txt/cord-316474-407bthqj.txt
cache: ./cache/cord-316474-407bthqj.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/molecules16010694
doi: 10.3390/molecules16010694
summary:
  Since the pioneering work described above, phage display technology has further been developed and improved by scientists from various fields, and its applications has extended from epitope mapping to antibody engineering and organ targeting [2] [3] [4] [5] . Mimotopes can now be obtained in a relatively cheap, efficient and convenient way, i.e. screening phage-displayed random peptide libraries with a given target. In this review, we will summarize the special databases, algorithms, programs, web servers and their applications in the phage display area, focusing on the tools for mimotope-based epitope mapping. With these tools, phage display technology has shown its power in exploring the interactions between proteins, peptides and small molecule ligands. Powered by special computational tools developed for phage display technology, not only linear epitope but also conformational epitope formed by discontinuous residues brought into spatial proximity by protein folding can be mapped reasonably.

abstract:
  Databases and computational tools for mimotopes have been an important part of phage display study. Five special databases and eighteen algorithms, programs and web servers and their applications are reviewed in this paper. Although these bioinformatics resources have been widely used to exclude target-unrelated peptides, characterize small molecules-protein interactions and map protein-protein interactions, a lot of problems are still waiting to be solved. With the improvement of these tools, they are expected to serve the phage display community better.


id: cord-320143-08gk0nmi
title: Antioxidant Potential of Antiviral Drug Umifenovir
author: Proskurnina, Elena V.
date: 2020-03-30
url: https://www.ncbi.nlm.nih.gov/pubmed/32235534/
doi: 10.3390/molecules25071577
abstract:
  Free radical reactions play an important role in biological functions of living systems. The balance between oxidants and antioxidants is necessary for the normal homeostasis of cells and organisms. Experimental works demonstrate the role of oxidative stress that is caused by influenza virus as well as the toxic effects of some antiviral drugs. Therefore, antiviral drugs should be characterized by its pro- and antioxidant activity, because it can affect its therapeutic efficiency. The aim of the study was to quantify the antioxidant capacity and propose the mechanism of the antioxidant effect of the antiviral drug Umifenovir (Arbidol(®)). The kinetic chemiluminescence with the 2,2’-azobis (2-amidinopropane) dihydrochloride + luminol system was used to quantify the antioxidant capacity of Umifenovir relative to the standard compound Trolox. With computer simulation, the reaction scheme and rate constants were proposed. The antioxidant capacity of 0.9 μM Umifenovir (maximum concentration of Umifenovir in blood after oral administration of 200 mg) was as high as 1.65 ± 0.18 μM of Trolox. Thus, the total antioxidant capacity of Umifenovir is comparable to the antioxidant capacity of Trolox. Unlike Trolox, Umifenovir reacts with free radicals in two stages. For Trolox, the free radical scavenging rate constant was k = 2000 nM(−1) min.(−1), for Umifenovir k(1) = 300 nM(−1)min.(−1), k(2) = 4 nM(−1)min.(−1). Slower kinetics of Umifenovir provides the prolonged antioxidant effect when compared to Trolox. This phenomenon can make a serious contribution to the compensation of oxidative stress that is caused by a viral disease and the therapeutic effect of the drug.


id: cord-324829-0nz0qioh
title: Applications of Gold Nanoparticles in Nanomedicine: Recent Advances in Vaccines †
author: Carabineiro, Sónia Alexandra Correia
date: 2017-05-22
txt: ./txt/cord-324829-0nz0qioh.txt
cache: ./cache/cord-324829-0nz0qioh.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28531163/
doi: 10.3390/molecules22050857
summary:
  Gold nanoparticles, in general, have remarkably high surface-to-volume ratio, are biocompatible and inert, and can be easily functionalized with several molecules; thus, they can also play an important role in the vaccine field as adjuvants, reducing toxicity, enhancing immunogenic activity, and providing stability of vaccine in storage, and have great potential as carriers for the development of a great diversity of fully synthetic vaccines [8] [9] [10] [11] [12] 15, 20, 21, 26, [48] [49] [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] [60] [61] . Gold nanoparticles, in general, have remarkably high surface-to-volume ratio, are biocompatible and inert, and can be easily functionalized with several molecules; thus, they can also play an important role in the vaccine field as adjuvants, reducing toxicity, enhancing immunogenic activity, and providing stability of vaccine in storage, and have great potential as carriers for the development of a great diversity of fully synthetic vaccines [8] [9] [10] [11] [12] 15, 20, 21, 26, [48] [49] [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] [60] [61] .

abstract:
  Nowadays, gold is used in (nano-)medicine, usually in the form of nanoparticles, due to the solid proofs given of its therapeutic effects on several diseases. Gold also plays an important role in the vaccine field as an adjuvant and a carrier, reducing toxicity, enhancing immunogenic activity, and providing stability in storage. An even brighter golden future is expected for gold applications in this area.


id: cord-330253-9sqizkio
author: Mowaka, Shereen
date: 2020-09-15
txt: ./txt/cord-330253-9sqizkio.txt
cache: ./cache/cord-330253-9sqizkio.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32942678/
doi: 10.3390/molecules25184232
summary:
  Six different batches of blank human plasma, OTN raw material (99.0%), Alogliptin raw material, internal standard (IS) (99.2%), Marizev ® (12.5 mg) tablets, tertiary butyl methyl ether (TBME), diethyl ether (DEE) were kindly donated by the British University in Egypt (CDRD, BUE) based on previous research collaborations (Repositioning CDRD-BUE project). Therefore, an advanced analytical technique and enhanced extraction of drugs from human plasma become a challenging approach that greatly affects pharmacokinetics, other clinical studies based on the drug C min and C max values and the bio-analytical methods sensitivity. The authors mentioned in the current study modified the rats'' plasma method [18] in another repositioning publication [11] but with direct precipitation with acetonitrile, the LLOQ was 50 ng/mL which is very high in comparison to the LLOQ in the current work with the enhanced extraction technique (9.98 ng/mL equivalent to 25 nM).

title:
  Enhanced Extraction Technique of Omarigliptin from Human Plasma—Applied to Biological Samples from Healthy Human Volunteers

abstract:
  Enhancing drug extraction from human plasma is a challenging approach that critically affects pharmacokinetic and any further clinical studies based on the drug C(min) and C(max) values. It also has a serious impact on the sensitivity and the lower limit of quantification (LLOQ) value of the bio-analytical methods. An advanced liquid chromatography tandem mass spectrometry (LC-MS/MS) bio-analytical method of omarigliptin (25–1000 nM) was established in human plasma using one-step liquid-liquid extraction. Alogliptin was used as an internal standard (IS) to attain good recovery and reproducibility while reducing the effects of the matrix. Enhanced plasma extraction of omarigliptin was successfully achieved with tertiary butyl methyl ether—diethyl ether (TBME-DEE) mixture as the extracting solvent, while using acetonitrile as the diluent solvent for the IS to effectively decrease the formed emulsion. Multiple Reaction Monitoring (MRM) of the transition pairs of m/z 399.2 to 153.0 for omarigliptin and m/z 340.2 to 116.0 for alogliptin was employed in positive Electro Spray Ionization (ESI) mode. Human plasma samples were collected after 1.5 h (t(max)) of Marizev(®) (12.5 mg) tablets administration to healthy human volunteers showing average concentration of 292.18 nM. Validation results were all satisfactory including successful stability studies with bias below 12%. The proposed study will be valuable for ethnicity comparison studies that will be commenced on omarigliptin in Egypt by the authors in prospective study, following the FDA recommends, to evaluate possible sub-group dissimilarities that include pharmacokinetic parameters.


id: cord-330813-43l9m0yh
author: Ishihara, Masayuki
date: 2020-10-01
txt: ./txt/cord-330813-43l9m0yh.txt
cache: ./cache/cord-330813-43l9m0yh.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/molecules25194502
doi: 10.3390/molecules25194502
summary:
  These results suggest that the insoluble powder was CaCO3 generated by an interaction between Ca 2+ ions in BiSCaO Water and CO2 in the air, and that the BiSCaO suspension, dispersion, and colloidal dispersion contained insoluble CaO and/or Ca(OH)2 in the form of micro-/nano-particles or precipitates that provide hydroxyl ions (OH -) to maintain the alkaline pH. Although the CFU/mL for TC and CF following treatment with undiluted (final two-fold diluted) BiSCaO Water and 0.4 (final 0.2 wt.%) BiSCaO suspension, dispersion, and colloidal dispersion exhibited high disinfection activities (>5 log decreases in CFU/mL), a small part of TC (>1000 CFU/mL) and CF (>100 CFU/mL) remained viable (Figure 7) . Although the CFU/mL for TC and CF following treatment with undiluted (final two-fold diluted) BiSCaO Water and 0.4 (final 0.2 wt.%) BiSCaO suspension, dispersion, and colloidal dispersion exhibited high disinfection activities (>5 log decreases in CFU/mL), a small part of TC (>1000 CFU/mL) and CF (>100 CFU/mL) remained viable (Figure 7) .

title:
  Safety of Concentrated Bioshell Calcium Oxide Water Application for Surface and Skin Disinfections against Pathogenic Microbes

abstract:
  Immediately post-production, commercially available bioshell calcium oxide (BiSCaO) water is colorless, transparent, and strongly alkaline (pH 12.8), and is known to possess deodorizing properties and broad microbicidal activity. However, BiSCaO Water may represent a serious safety risk to the living body, given the strong alkalinity. This study aimed to investigate the safety of BiSCaO Water for use as an antiseptic/disinfectant despite concerns regarding its high alkalinity. The change over time in pH of BiSCaO Water was measured during air contact (stirring BiSCaO Water in ambient air). When sprayed on metal, plastic, wood piece, paper, and skin surfaces, the pH of BiSCaO Water decreased rapidly, providing a white powder coating upon drying. Scanning electron microscopy images, energy dispersive X-ray elemental mapping, and X-ray diffractograms showed that the dried powder residues of BiSCaO Water were composed primarily of calcium carbonate. These results suggested that BiSCaO Water is a potent reagent that may overcome the obstacles of being strongly alkaline, making this material appropriate for use in disinfection against pathogenic microbes.


id: cord-331504-b68y9hxw
title: New Isoxazolidine-Conjugates of Quinazolinones—Synthesis, Antiviral and Cytostatic Activity
author: Piotrowska, Dorota G.
date: 2016-07-22
txt: ./txt/cord-331504-b68y9hxw.txt
cache: ./cache/cord-331504-b68y9hxw.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/27455228/
doi: 10.3390/molecules21070959
summary:
  Our synthetic strategy to compounds trans-11/cis-11 relies on the 1,3-dipolar cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone 12 [36] with 2-vinyl-3H-quinazolin-4-ones 13 substituted at N3 (Scheme 1). Our synthetic strategy to compounds trans-11/cis-11 relies on the 1,3-dipolar cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone 12 [36] with 2-vinyl-3H-quinazolin-4-ones 13 substituted at N3 (Scheme 1). Our synthetic strategy to compounds trans-11/cis-11 relies on the 1,3-dipolar cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone 12 [36] with 2-vinyl-3H-quinazolin-4-ones 13 substituted at N3 (Scheme 1). However, attempts to isolate pure diastereoisomers were fruitful for trans-11a The relative configurations of isoxazolidines trans-11a and cis-11a were established based on our previous studies on stereochemistry of cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone (12) with various vinyl aryls [39, 40] since similar 1 H-NMR spectral patters for the respective series of trans-and cis-isoxazolidines were observed. After incubation at 37˝C for two (L1210), three (CEM) or four (HeLa) days, the cell number was determined of isoxazolidine-containing quinazolinones trans-11 and cis-11 have been synthesised from N-methyl-C-diethoxyphosphorylnitrone (12) and the respective N3-substituted 2-vinyl-quinazolin-ones 13 via the 1,3-dipolar cycloaddition.

abstract:
  A novel series of (3-diethoxyphosphoryl)isoxazolidines substituted at C5 with various quinazolinones have been synthesized by the 1,3-dipolar cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone with N3-substitued 2-vinyl-3H-quinazolin-4-ones. All isoxazolidines were assessed for antiviral activity against a broad range of DNA and RNA viruses. Isoxazolidines trans-11f/cis-11f (90:10), trans-11h and trans-11i/cis-11i (97:3) showed weak activity (EC(50) = 6.84, 15.29 and 9.44 μM) toward VZV (TK(+) strain) which was only one order of magnitude lower than that of acyclovir used as a reference drug. Phosphonates trans-11b/cis-11b (90:10), trans-11c, trans-11e/cis-11e (90:10) and trans-11g appeared slightly active toward cytomegalovirus (EC(50) = 27–45 μM). Compounds containing benzyl substituents at N3 in the quinazolinone skeleton exhibited slight antiproliferative activity towards the tested immortalized cells with IC(50) in the 21–102 μM range.


id: cord-334511-lx9608vy
title: NMR as a “Gold Standard” Method in Drug Design and Discovery
author: Emwas, Abdul-Hamid
date: 2020-10-09
txt: ./txt/cord-334511-lx9608vy.txt
cache: ./cache/cord-334511-lx9608vy.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/molecules25204597
doi: 10.3390/molecules25204597
summary:
  The nearly ubiquitous use of virtual screening is due to its efficiency in searching massive chemical databases in order to generate lead molecules [313] that inhibit protein-protein interactions [314] , and its ability to help identity ligand (drug) binding sites on the target of interest [310] to lend insight to the mechanisms of action for lead compounds [315, 316] . The nearly ubiquitous use of virtual screening is due to its efficiency in searching massive chemical databases in order to generate lead molecules [313] that inhibit protein-protein interactions [314] , and its ability to help identity ligand (drug) binding sites on the target of interest [310] to lend insight to the mechanisms of action for lead compounds [315, 316] . Clearly, combining virtual screening with NMR-based methods is advantageous in studying how ligands (drugs) bind and interact with targets (proteins) of interest. The interactions between targets (proteins) and ligands (small molecules) can be analyzed independently of the biological systems by using ''cell-based'' NMR drug design approaches.

abstract:
  Studying disease models at the molecular level is vital for drug development in order to improve treatment and prevent a wide range of human pathologies. Microbial infections are still a major challenge because pathogens rapidly and continually evolve developing drug resistance. Cancer cells also change genetically, and current therapeutic techniques may be (or may become) ineffective in many cases. The pathology of many neurological diseases remains an enigma, and the exact etiology and underlying mechanisms are still largely unknown. Viral infections spread and develop much more quickly than does the corresponding research needed to prevent and combat these infections; the present and most relevant outbreak of SARS-CoV-2, which originated in Wuhan, China, illustrates the critical and immediate need to improve drug design and development techniques. Modern day drug discovery is a time-consuming, expensive process. Each new drug takes in excess of 10 years to develop and costs on average more than a billion US dollars. This demonstrates the need of a complete redesign or novel strategies. Nuclear Magnetic Resonance (NMR) has played a critical role in drug discovery ever since its introduction several decades ago. In just three decades, NMR has become a “gold standard” platform technology in medical and pharmacology studies. In this review, we present the major applications of NMR spectroscopy in medical drug discovery and development. The basic concepts, theories, and applications of the most commonly used NMR techniques are presented. We also summarize the advantages and limitations of the primary NMR methods in drug development.


id: cord-340879-gu91cact
author: Li, Miao
date: 2017-01-23
txt: ./txt/cord-340879-gu91cact.txt
cache: ./cache/cord-340879-gu91cact.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28125005/
doi: 10.3390/molecules22010187
summary:
  title: Isolation and Characterization of a Phaseolus vulgaris Trypsin Inhibitor with Antiproliferative Activity on Leukemia and Lymphoma Cells The intent of the present study was to isolate a trypsin inhibitor from the gold bean and to test it for inhibitory action on tumor cells, viral enzymes, and fungal growth. Gold bean trypsin inhibitor is also devoid of any inhibitory effect on HIV-1 integrase and SARS coronavirus proteinase. Gold bean trypsin inhibitor is also devoid of any inhibitory effect on HIV-1 integrase and SARS coronavirus proteinase. A lectin, an antifungal protein and a trypsin inhibitor can be isolated from the gold bean [24, 25] . A homodimeric sporamin-type trypsin inhibitor with antiproliferative, hiv reverse transcriptase-inhibitory and antifungal activities from wampee (clausena lansium) seeds The isolation of two proteins, glycoprotein i and a trypsin inhibitor, from the seeds of kidney bean (Phaseolus vulgaris)

title:
  Isolation and Characterization of a Phaseolus vulgaris Trypsin Inhibitor with Antiproliferative Activity on Leukemia and Lymphoma Cells

abstract:
  A 17.5-kDa trypsin inhibitor was purified from Phaseolus vulgaris cv. “gold bean” with an isolation protocol including ion exchange chromatography on DEAE-cellulose (Diethylaminoethyl-cellulose), affinity chromatography on Affi-gel blue gel, ion exchange chromatography on SP-sepharose (Sulfopropyl-sepharose), and gel filtration by FPLC (Fast protein liquid chromatography) on Superdex 75. It dose-dependently inhibited trypsin with an IC(50) value of 0.4 μM, and this activity was reduced in the presence of dithiothreitol in a dose- and time-dependent manner, signifying the importance of the disulfide linkage to the activity. It inhibited [methyl-(3)H] thymidine incorporation by leukemia L1210 cells and lymphoma MBL2 cells with an IC(50) value of 2.3 μM and 2.5 μM, respectively. The inhibitor had no effect on fungal growth and the activities of various viral enzymes when tested up to 100 μM.


id: cord-344175-e2m9o8c2
title: COVID-19, Chloroquine Repurposing, and Cardiac Safety Concern: Chirality Might Help
author: Lentini, Giovanni
date: 2020-04-16
url: https://www.ncbi.nlm.nih.gov/pubmed/32316270/
doi: 10.3390/molecules25081834
abstract:
  The desperate need to find drugs for COVID-19 has indicated repurposing strategies as our quickest way to obtain efficacious medicines. One of the options under investigation is the old antimalarial drug, chloroquine, and its analog, hydroxychloroquine. Developed as synthetic succedanea of cinchona alkaloids, these chiral antimalarials are currently in use as the racemate. Besides the ethical concern related to accelerated large-scale clinical trials of drugs with unproven efficacy, the known potential detrimental cardiac effects of these drugs should also be considered. In principle, the safety profile might be ameliorated by using chloroquine/hydroxychloroquine single enantiomers in place of the racemate.


id: cord-347992-coby2m6e
author: Marton, Soledad
date: 2010-06-28
txt: ./txt/cord-347992-coby2m6e.txt
cache: ./cache/cord-347992-coby2m6e.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/20657381/
doi: 10.3390/molecules15074610
summary:
  Although ribozymes and DNAzymes have been extensively assayed as potential therapeutic agents, and different clinical trials have already tested their efficiency against various diseases [49] [50] [51] [52] , very few reports have described the direct application of in vitro selection strategies in the development of potentially therapeutic catalytic nucleic acids. Molecular studies have shown that this aptamer binds to the cell surface protein nucleolin and inhibits the activity of NF-KB, a ubiquitous transcription factor, through intracellular complex formation [108] . In a different approach, SELEX has been performed with the E2F1 protein to find in vitro selected RNA aptamers that bind to and inhibit E2F activity. Astier-Gi''s group described the characterization of two DNA aptamers (27v and 127v) that specifically bind to hepatitis C virus (HCV) RNA polymerase (NS5B), inhibiting its activity in vitro [146] . In vitro selection procedures for identifying DNA and RNA aptamers targeted to nucleic acids and proteins

title:
  In Vitro and Ex Vivo Selection Procedures for Identifying Potentially Therapeutic DNA and RNA Molecules

abstract:
  It was only relatively recently discovered that nucleic acids participate in a variety of biological functions, besides the storage and transmission of genetic information. Quite apart from the nucleotide sequence, it is now clear that the structure of a nucleic acid plays an essential role in its functionality, enabling catalysis and specific binding reactions. In vitro selection and evolution strategies have been extremely useful in the analysis of functional RNA and DNA molecules, helping to expand our knowledge of their functional repertoire and to identify and optimize DNA and RNA molecules with potential therapeutic and diagnostic applications. The great progress made in this field has prompted the development of ex vivo methods for selecting functional nucleic acids in the cellular environment. This review summarizes the most important and most recent applications of in vitro and ex vivo selection strategies aimed at exploring the therapeutic potential of nucleic acids.


id: cord-349672-2kt7xw8i
title: Mechanism of Type IA Topoisomerases
author: Dasgupta, Tumpa
date: 2020-10-17
txt: ./txt/cord-349672-2kt7xw8i.txt
cache: ./cache/cord-349672-2kt7xw8i.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/molecules25204769
doi: 10.3390/molecules25204769
summary:
  Here, based on available structural and biochemical data, we discuss how a type IA topoisomerase may recognize and bind single-stranded DNA or RNA to initiate its required catalytic function. In type IA topoisomerases, the hydroxyl group in the side chain of the active site tyrosine residue is responsible for the first nucleophilic attack on the scissile phosphate of a single-stranded DNA resulting in the cleavage of the G-strand and the formation of the transient 5 -phospho-tyrosyl covalent linkage [66] . Though the type IA topoisomerase core domain that forms the characteristic torus structure contains all the highly conserved motifs responsible for G-strand binding and cleavage religation, the C-terminal domains of bacterial topoisomerase I have been shown to be required for removing negative supercoils from DNA rapidly in a processive mechanism [61, 72, [84] [85] [86] [87] .

abstract:
  Topoisomerases in the type IA subfamily can catalyze change in topology for both DNA and RNA substrates. A type IA topoisomerase may have been present in a last universal common ancestor (LUCA) with an RNA genome. Type IA topoisomerases have since evolved to catalyze the resolution of topological barriers encountered by genomes that require the passing of nucleic acid strand(s) through a break on a single DNA or RNA strand. Here, based on available structural and biochemical data, we discuss how a type IA topoisomerase may recognize and bind single-stranded DNA or RNA to initiate its required catalytic function. Active site residues assist in the nucleophilic attack of a phosphodiester bond between two nucleotides to form a covalent intermediate with a 5′-phosphotyrosine linkage to the cleaved nucleic acid. A divalent ion interaction helps to position the 3′-hydroxyl group at the precise location required for the cleaved phosphodiester bond to be rejoined following the passage of another nucleic acid strand through the break. In addition to type IA topoisomerase structures observed by X-ray crystallography, we now have evidence from biophysical studies for the dynamic conformations that are required for type IA topoisomerases to catalyze the change in the topology of the nucleic acid substrates.


id: cord-352513-15nalst7
title: Recent Advances in Microfluidic Paper-Based Analytical Devices toward High-Throughput Screening
author: Boobphahom, Siraprapa
date: 2020-06-28
txt: ./txt/cord-352513-15nalst7.txt
cache: ./cache/cord-352513-15nalst7.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/molecules25132970
doi: 10.3390/molecules25132970
summary:
  Electrophoretic separation technique has been used in µPADs as a sample preparation step in various analytical detection methods such as ion-transmission mass spectrometry (MS) for analysis of amino acids [97] , matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) for detection of albumin and glycated hemoglobin (HBA1c) [98] , and lateral flow immunoassay (LFA) for the detection of IgG [90] Typically, fluid control and programmability are vital to automate and to minimize the processing in the fabrication and the operation, but maximize the use of µPADs. By controlling the fluid flow in the µPAD, researchers have been able to achieve high-sensitivity detection and automated programmable assays [99, 100] . Even though µPADs provide extraordinary advantages, including simple fabrication and mass-scalability at an affordable cost, if an advanced paper-based analytical device providing high performance and sensitivity is to be achieved, suitable detection mechanisms are necessary for the µPADs. The most common detection techniques in µPADs are colorimetric, electrochemical, chemiluminescent, and electrochemiluminescent techniques.

abstract:
  Microfluidic paper-based analytical devices (µPADs) have become promising tools offering various analytical applications for chemical and biological assays at the point-of-care (POC). Compared to traditional microfluidic devices, µPADs offer notable advantages; they are cost-effective, easily fabricated, disposable, and portable. Because of our better understanding and advanced engineering of µPADs, multistep assays, high detection sensitivity, and rapid result readout have become possible, and recently developed µPADs have gained extensive interest in parallel analyses to detect biomarkers of interest. In this review, we focus on recent developments in order to achieve µPADs with high-throughput capability. We discuss existing fabrication techniques and designs, and we introduce and discuss current detection methods and their applications to multiplexed detection assays in relation to clinical diagnosis, drug analysis and screening, environmental monitoring, and food and beverage quality control. A summary with future perspectives for µPADs is also presented.


id: cord-352891-ljmkqdzx
author: Parang, Keykavous
date: 2020-05-17
txt: ./txt/cord-352891-ljmkqdzx.txt
cache: ./cache/cord-352891-ljmkqdzx.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32429580/
doi: 10.3390/molecules25102343
summary:
  title: Comparative Antiviral Activity of Remdesivir and Anti-HIV Nucleoside Analogs against Human Coronavirus 229E (HCoV-229E) Herein, we report the antiviral activity of remdesivir against human coronavirus 229E (HCoV-229E) compared to known anti-HIV agents. These agents included tenofovir (TFV), 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA), alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC), known as nucleoside reverse-transcriptase inhibitors (NRTIs), and a number of 5′-O-fatty acylated anti-HIV nucleoside conjugates. Therefore, HCoV-229E may be a good initial model for the evaluation of antiviral compounds that could have potential applications against other coronaviruses, such as SARS-COV-2, the coronavirus that causes COVID-19. We have previously shown that the conjugation of certain fatty acids to the anti-HIV NRTIs, such as FLT, 3TC and FTC, enhanced activity against X4, R5, cell-associated, and/or multi-drug resistant virus when compared with their parent nucleosides [24] [25] [26] [27] . A series of anti-HIV nucleosides and their fatty acyl derivatives were compared with remdesivir for antiviral activity against HCoV-229E in MRC-5 cells.

title:
  Comparative Antiviral Activity of Remdesivir and Anti-HIV Nucleoside Analogs against Human Coronavirus 229E (HCoV-229E)

abstract:
  Remdesivir is a nucleotide prodrug that is currently undergoing extensive clinical trials for the treatment of COVID-19. The prodrug is metabolized to its active triphosphate form and interferes with the action of RNA-dependent RNA polymerase of SARS-COV-2. Herein, we report the antiviral activity of remdesivir against human coronavirus 229E (HCoV-229E) compared to known anti-HIV agents. These agents included tenofovir (TFV), 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA), alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC), known as nucleoside reverse-transcriptase inhibitors (NRTIs), and a number of 5′-O-fatty acylated anti-HIV nucleoside conjugates. The anti-HIV nucleosides interfere with HIV RNA-dependent DNA polymerase and/or act as chain terminators. Normal human fibroblast lung cells (MRC-5) were used to determine the cytotoxicity of the compounds. The study revealed that remdesivir exhibited an EC(50) value of 0.07 µM against HCoV-229E with TC(50) of > 2.00 µM against MRC-5 cells. Parent NRTIs were found to be inactive against (HCoV-229E) at tested concentrations. Among all the NRTIs and 5′-O-fatty acyl conjugates of NRTIs, 5′-O-tetradecanoyl ester conjugate of FTC showed modest activity with EC(50) and TC(50) values of 72.8 µM and 87.5 µM, respectively. These data can be used for the design of potential compounds against other coronaviruses.


id: cord-353494-72fvkx7f
title: Protease Inhibitory Effect of Natural Polyphenolic Compounds on SARS-CoV-2: An In Silico Study
author: Singh, Rajveer
date: 2020-10-10
txt: ./txt/cord-353494-72fvkx7f.txt
cache: ./cache/cord-353494-72fvkx7f.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/molecules25204604
doi: 10.3390/molecules25204604
summary:
  The RMSD plots of all the three ligand-protein complexes showed very stable conformation throughout the simulation study, which demonstrates that it has a huge impact on the Mpro target ( Figure S2A ) as the reference compound N3. RMSF study of the three natural compounds with SARS-COV-2 Mpro showed very less fluctuations, and the value was found to be less than 0.2 nm, which indicates that the ligands bind properly with the active sites of the protein such as the reference compounds ( Figure S3A ). RMSF study of the three natural compounds with SARS-COV-2 Mpro showed very less fluctuations, and the value was found to be less than 0.2 nm, which indicates that the ligands bind properly with the active sites of the protein such as the reference compounds ( Figure S3A ). The molecular dynamic simulation showed that the selected natural compounds bind and stabilized the active site of both the proteins such as Mpro and TMPRSS2.

abstract:
  The current pandemic, caused by SARS-CoV-2 virus, is a severe challenge for human health and the world economy. There is an urgent need for development of drugs that can manage this pandemic, as it has already infected 19 million people and led to the death of around 711,277 people worldwide. At this time, in-silico studies are providing lots of preliminary data about potential drugs, which can be a great help in further in-vitro and in-vivo studies. Here, we have selected three polyphenolic compounds, mangiferin, glucogallin, and phlorizin. These compounds are isolated from different natural sources but share structural similarities and have been reported for their antiviral activity. The objective of this study is to analyze and predict the anti-protease activity of these compounds on SARS-CoV-2main protease (Mpro) and TMPRSS2 protein. Both the viral protein and the host protein play an important role in the viral life cycle, such as post-translational modification and viral spike protein priming. This study has been performed by molecular docking of the compounds using PyRx with AutoDock Vina on the two aforementioned targets chosen for this study, i.e., SARS-CoV-2 Mpro and TMPRSS2. The compounds showed good binding affinity and are further analyzed by (Molecular dynamic) MD and Molecular Mechanics Poisson-Boltzmann Surface Area MM-PBSA study. The MD-simulation study has predicted that these natural compounds will have a great impact on the stabilization of the binding cavity of the Mpro of SARS-CoV-2. The predicted pharmacokinetic parameters also show that these compounds are expected to have good solubility and absorption properties. Further predictions for these compounds also showed no involvement in drug-drug interaction and no toxicity.


id: cord-355685-wgad0eoh
author: Francesconi, Valeria
date: 2020-03-25
txt: ./txt/cord-355685-wgad0eoh.txt
cache: ./cache/cord-355685-wgad0eoh.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32218301/
doi: 10.3390/molecules25071487
summary:
  Compounds 6, 8, 16 and 17, bearing the 5-(thio)semicarbazone and 5-hydrazone functionalities in combination with the 2-benzyl ring on the benzimidazole core structure, acted as dual inhibitors of influenza A virus and human coronavirus. For respiratory syncytial virus (RSV), activity is limited to the 5-thiosemicarbazone (25) and 5-hydrazone (22) compounds carrying the 2-[(benzotriazol-1/2-yl)methyl]benzimidazole scaffold. The herein-investigated benzimidazole-based derivatives may represent valuable hit compounds, deserving subsequent structural improvements towards more efficient antiviral agents for the treatment of pathologies caused by these human respiratory viruses. For RSV, activity is restricted to the 5-(thio)semicarbazone (25) and hydrazone (22) compounds carrying the 2-[(benzotriazol-1/2-yl)methyl]benzimidazole scaffold, in line with the previously synthesized analogues (see above), which show comparable potency in the low micromolar range. In summary, this study reports the synthesis of a series of (thio)semicarbazone-and hydrazone-containing benzimidazoles for the development of novel antiviral agents which have shown the ability to inhibit the replication of three human respiratory viruses.

title:
  Synthesis and Biological Evaluation of Novel (thio)semicarbazone-Based Benzimidazoles as Antiviral Agents against Human Respiratory Viruses

abstract:
  Respiratory RNA viruses are responsible for recurrent acute respiratory illnesses that still represent a major medical need. Previously we developed a large variety of benzimidazole derivatives able to inhibit these viruses. Herein, two series of (thio)semicarbazone- and hydrazone-based benzimidazoles have been explored, by derivatizing 5-acetyl benzimidazoles previously reported by us, thereby evaluating the influence of the modification on the antiviral activity. Compounds 6, 8, 16 and 17, bearing the 5-(thio)semicarbazone and 5-hydrazone functionalities in combination with the 2-benzyl ring on the benzimidazole core structure, acted as dual inhibitors of influenza A virus and human coronavirus. For respiratory syncytial virus (RSV), activity is limited to the 5-thiosemicarbazone (25) and 5-hydrazone (22) compounds carrying the 2-[(benzotriazol-1/2-yl)methyl]benzimidazole scaffold. These molecules proved to be the most effective antiviral agents, able to reach the potency profile of the licensed drug ribavirin. The molecular docking analysis explained the SAR of these compounds around their binding mode to the target RSV F protein, revealing the key contacts for further assessment. The herein-investigated benzimidazole-based derivatives may represent valuable hit compounds, deserving subsequent structural improvements towards more efficient antiviral agents for the treatment of pathologies caused by these human respiratory viruses.


