4.5 Article

Benzohydroxamic acids as potent and selective anti-HCV agents

Journal

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 23, Issue 21, Pages 5936-5940

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2013.08.081

Keywords

Benzohydroxamic acids; Hepatitis C virus; Poliomyelitis virus; Metal-depending enzymes

Funding

  1. Russian Foundation for Basic Research [11-04-01202]
  2. program of the Presidium of the Russian Academy of Sciences 'Molecular and Cell Biology'

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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. (C) 2013 Elsevier Ltd. All rights reserved.

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