Development of novel ferulic acid derivatives as potent histone deacetylase inhibitors

Bioorg Med Chem. 2013 Nov 15;21(22):6973-80. doi: 10.1016/j.bmc.2013.09.021. Epub 2013 Sep 19.

Abstract

Histone deacetylase inhibitors (HDACIs) offer a promising strategy for cancer therapy. The discovery of potent ferulic acid-based HDACIs with hydroxamic acid or 2-aminobenzamide group as zinc binding group was reported. The halogeno-acetanilide was introduced as novel surface recognition moiety (SRM). The majority of title compounds displayed potent HDAC inhibitory activity. In particular, FA6 and FA16 exhibited significant enzymatic inhibitory activities, with IC50 values of 3.94 and 2.82 μM, respectively. Furthermore, these compounds showed moderate antiproliferative activity against a panel of human cancer cells. FA17 displayed promising profile as an antitumor candidate. The results indicated that these ferulic acid derivatives could serve as promising lead compounds for further optimization.

Keywords: Anticancer; Ferulic acid; HDAC inhibitor; Histone deacetylase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Binding Sites
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Coumaric Acids / chemistry*
  • Coumaric Acids / metabolism
  • Coumaric Acids / pharmacology
  • Enzyme Activation / drug effects
  • Histone Deacetylase Inhibitors / chemistry*
  • Histone Deacetylase Inhibitors / metabolism
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / chemistry*
  • Histone Deacetylases / metabolism
  • Humans
  • Molecular Docking Simulation
  • Protein Structure, Tertiary

Substances

  • Antineoplastic Agents
  • Coumaric Acids
  • Histone Deacetylase Inhibitors
  • ferulic acid
  • Histone Deacetylases