Synthesis of N'-propylhydrazide analogs of hydroxamic inhibitors of histone deacetylases (HDACs) and evaluation of their impact on activities of HDACs and replication of hepatitis C virus (HCV)

  • Bioorg Med Chem Lett. 2019 Aug 15;29(16):2369-2374. doi: 10.1016/j.bmcl.2019.06.006.
Maxim V Kozlov  1 ,  Konstantin A Konduktorov  2 ,  Anastasia S Shcherbakova  2 ,  Sergey N Kochetkov  2
Affiliations
  • 1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova 32, Moscow 119991, Russia. Electronic address: [email protected].
  • 2. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova 32, Moscow 119991, Russia.
PMID: 31201063 DOI: 10.1016/j.bmcl.2019.06.006
Abstract

N'-Propylhydrazide analogs of hydroxamic inhibitors of histone deacetylases (HDACs), including tubastatin A, vorinostat and belinostat, were synthesized. All prepared compounds inhibited HDAC1/2/3, but not HDAC6, except for one hydrazide analog of HDAC4/5/7 inhibitor that was completely inactive. A novel 4-substituted derivative of N'-propylbenzohydrazide with extremely high anti-HCV activity was discovered.

Keywords
HCV; HDAC; Hydroxamic acid; Inhibitor; N′-Propylhydrazide; Pharmacophore.