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.
Maxim V Kozlov  1 ,  Alla A Kleymenova  2 ,  Lyudmila I Romanova  3 ,  Konstantin A Konduktorov  2 ,  Kamila A Kamarova  2 ,  Olga A Smirnova  2 ,  Vladimir S Prassolov  2 ,  Sergey N Kochetkov  2
Affiliations
  • 1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str. 32, 119991 Moscow, Russia. Electronic address: [email protected].
  • 2. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Str. 32, 119991 Moscow, Russia.
  • 3. Chumakov Institute of Poliomyelitis, Russian Academy of Medical Sciences, 142782 Moscow Region, Russia.
PMID: 25937017 DOI: 10.1016/j.bmcl.2015.04.016
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.
Products