Design, synthesis and preliminary bioactivity evaluations of substituted quinoline hydroxamic acid derivatives as novel histone deacetylase (HDAC) inhibitors

Bioorg Med Chem. 2015 Aug 1;23(15):4364-4374. doi: 10.1016/j.bmc.2015.06.024. Epub 2015 Jun 17.

Abstract

Inhibition of HDACs activity has become a promising therapeutic strategy in clinical practice to reverse the abnormal epigenetic states of cancer and other diseases. Therefore, HDAC inhibitors become a relatively new class of anti-cancer agent. In the present study, we reported the design and synthesis of a series of novel HDAC inhibitors using various substituted quinoline rings as the cap group. In vitro studies showed that some compounds have good inhibitory activities against HDACs and potent antiproliferative activities in some tumor cell lines. Especially, compound 9w (IC50=85 nM), exhibited better inhibitory effect compared with SAHA (IC50=161 nM).

Keywords: Anti-proliferative; HDAC; Hydroxamic acid; Inhibitor; Quinoline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • Histone Deacetylase Inhibitors / chemical synthesis*
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / toxicity
  • Histone Deacetylases / chemistry*
  • Histone Deacetylases / metabolism
  • Humans
  • Hydroxamic Acids / chemical synthesis
  • Hydroxamic Acids / chemistry*
  • Hydroxamic Acids / toxicity
  • Molecular Docking Simulation
  • Protein Structure, Tertiary
  • Quinolines / chemistry
  • Structure-Activity Relationship

Substances

  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Quinolines
  • quinoline
  • Histone Deacetylases