Abstract
Synthesis of serine derivatives having the essential functional groups for the inhibitor of SARS 3CL protease and evaluation of their inhibitory activities using SARS 3CL R188I mutant protease are described. The lead compounds, functionalized serine derivatives, were designed based on the tetrapeptide aldehyde and Bai's cinnamoly inhibitor, and additionally performed with simulation on GOLD softwear. Structure activity relationship studies of the candidate compounds were given reasonable inhibitors ent-3 and ent-7k against SARS 3CL R188I mutant protease. These inhibitors showed protease selectivity and no cytotoxicity.
Keywords:
Cathepsin B; Cytotoxicity; Docking simulation; SARS 3CL protease; SARS CoV; Serine derivative.
Copyright © 2016 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Death / drug effects
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Coronavirus 3C Proteases
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Cysteine Endopeptidases / metabolism
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Dose-Response Relationship, Drug
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Drug Design*
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HeLa Cells
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Humans
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Molecular Docking Simulation
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Molecular Structure
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Protease Inhibitors / chemical synthesis*
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Protease Inhibitors / chemistry
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Protease Inhibitors / pharmacology*
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Serine / analogs & derivatives*
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Serine / chemical synthesis
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Serine / pharmacology
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Severe acute respiratory syndrome-related coronavirus / enzymology*
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Small Molecule Libraries / chemical synthesis
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Small Molecule Libraries / chemistry
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Small Molecule Libraries / pharmacology*
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Structure-Activity Relationship
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Viral Proteins / antagonists & inhibitors*
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Viral Proteins / metabolism
Substances
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Protease Inhibitors
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Small Molecule Libraries
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Viral Proteins
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Serine
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Cysteine Endopeptidases
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Coronavirus 3C Proteases