Pyridine hydroxamic acids are specific anti-HCV agents affecting HDAC6

Bioorg Med Chem Lett. 2015 Jun 1;25(11):2382-5. doi: 10.1016/j.bmcl.2015.04.016. Epub 2015 Apr 16.

Abstract

Recently we reported benzohydroxamic acids (BHAs) as potent and selective inhibitors of hepatitis C virus (HCV) replicon propagation. In this work 12 pyridine hydroxamic acids (PHAs) were synthesized and tested in full-genome replicon assay. It was found that PHAs possessed very similar anti-HCV properties compared to BHAs. Both classes of hydroxamic acids caused hyperacetylation of α-tubulin pointing to inhibition of histone deacetylase 6 (HDAC6) as part of their antiviral activity. The tested compounds did not inhibit the growth of poliovirus, displaying high selectivity against HCV.

Keywords: Benzohydroxamic acids; Hepatitis C virus; Histone deacetylase 6; Pyridine hydroxamic acids; α-Tubulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Cell Line, Tumor
  • Gene Expression Regulation / drug effects
  • Hepacivirus / drug effects*
  • Histone Deacetylase 6
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • Hydroxamic Acids / chemistry
  • Hydroxamic Acids / pharmacology*
  • Molecular Structure
  • Poliovirus / drug effects
  • Pyridines / chemistry*
  • Structure-Activity Relationship
  • Virus Replication / drug effects
  • Viruses

Substances

  • Antiviral Agents
  • Hydroxamic Acids
  • Pyridines
  • HDAC6 protein, human
  • Histone Deacetylase 6
  • Histone Deacetylases