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. Epub 2019 Jun 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Hepacivirus / drug effects*
  • Histone Deacetylase Inhibitors / chemical synthesis
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / metabolism
  • Humans
  • Hydrazines / chemical synthesis
  • Hydrazines / chemistry
  • Hydrazines / pharmacology*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / metabolism
  • Structure-Activity Relationship
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Histone Deacetylase Inhibitors
  • Hydrazines
  • Repressor Proteins
  • HDAC4 protein, human
  • HDAC5 protein, human
  • HDAC7 protein, human
  • Histone Deacetylases