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Benzohydroxamic acids as potent and selective anti-HCV agents
Authors:Maxim V. Kozlov  Alla A. Kleymenova  Lyudmila I. Romanova  Konstantin A. Konduktorov  Olga A. Smirnova  Vladimir S. Prasolov  Sergey N. Kochetkov
Affiliation:1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str. 32, 119991 Moscow, Russia;2. Chumakov Institute of Poliomyelitis, Russian Academy of Medical Sciences, 142782 Moscow Region, Russia
Abstract:A diverse collection of 40 derivatives of benzohydroxamic acid (BHAs) of various structural groups were synthesized and tested against hepatitis C virus (HCV) in full-genome replicon assay. Some of these compounds demonstrated an exceptional activity, suppressing viral replication at sub-micromolar concentrations. The compounds were inactive against key viral enzymes NS3, and NS5B in vitro assays, suggesting host cell inhibition target(s). The testing results were consistent with metal coordination by the BHAs hydroxamic group in complex with a target(s). Remarkably, this class of compounds did not suppress poliomyelitis virus (PV) propagation in RD cells indicating a specific antiviral activity of BHAs against HCV.
Keywords:Benzohydroxamic acids  Hepatitis C virus  Poliomyelitis virus  Metal-depending enzymes
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