Abstract
A series of C6-rigid S-DABO analogs characterized by a substituted benzoyl group at C6 position of the pyrimidine ring has been synthesized and biological evaluation as NNRTIs against wild-type HIV-1 strain IIIB, double RT mutant (K103N+Y181C) strain RES056 as well as HIV-2 strain ROD in MT-4 cell cultures. Most of the compounds exhibited moderate antiviral activities. Among them, compound 7q displayed the highest anti-HIV-1 activity with an EC50 value of 0.26μM and a selectivity index (SI) of 541. The preliminary structure-activity relationship (SAR) of these new S-DABOs was investigated, the target RT was confirmed and docking study was performed.
Keywords:
HIV-1 reverse transcriptase; NNRTIs; Rigid conformation; S-DABO; SAR.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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HIV Reverse Transcriptase / antagonists & inhibitors*
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HIV Reverse Transcriptase / metabolism
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HIV-1 / enzymology*
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Humans
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Molecular Docking Simulation
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Protein Binding
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Protein Structure, Tertiary
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Pyrimidines / chemical synthesis
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Pyrimidines / chemistry*
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Pyrimidines / metabolism
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Pyrimidinones / chemical synthesis*
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Pyrimidinones / chemistry
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Pyrimidinones / metabolism
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Reverse Transcriptase Inhibitors / chemical synthesis*
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Reverse Transcriptase Inhibitors / chemistry
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Reverse Transcriptase Inhibitors / metabolism
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Structure-Activity Relationship
Substances
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(4-methoxybenzylthio)-6-(3-chlorobenzoyl)-5-methylpyrimidin-4(3H)-one
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Pyrimidines
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Pyrimidinones
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Reverse Transcriptase Inhibitors
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reverse transcriptase, Human immunodeficiency virus 1
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HIV Reverse Transcriptase