title: Benzohydroxamic acids as potent and selective anti-HCV agents.
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.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str. 32, 119991 Moscow, Russia. Electronic address: kozlovmv@hotmail.com.
authors.forename: Maxim V
authors.initials: MV
authors.lastname: Kozlov
authors.forename: Alla A
authors.initials: AA
authors.lastname: Kleymenova
authors.forename: Lyudmila I
authors.initials: LI
authors.lastname: Romanova
authors.forename: Konstantin A
authors.initials: KA
authors.lastname: Konduktorov
authors.forename: Olga A
authors.initials: OA
authors.lastname: Smirnova
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Prasolov
authors.forename: Sergey N
authors.initials: SN
authors.lastname: Kochetkov
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D016679:Genome, Viral / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000494:pharmacology*; D017955:Poliovirus / Q000187:drug effects; D012093:Replicon / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D006877:Hydroxamic Acids; C006696:benzohydroxamic acid
keywords: Benzohydroxamic acids; Hepatitis C virus; Metal-depending enzymes; Poliomyelitis virus