Search for novel histone deacetylase inhibitors. Part II: design and synthesis of novel isoferulic acid derivatives

Bioorg Med Chem. 2014 May 1;22(9):2707-13. doi: 10.1016/j.bmc.2014.03.019. Epub 2014 Mar 22.

Abstract

Previously, we described the discovery of potent ferulic acid-based histone deacetylase inhibitors (HDACIs) with halogeno-acetanilide as novel surface recognition moiety (SRM). In order to improve the affinity and activity of these HDACIs, twenty seven isoferulic acid derivatives were described herein. The majority of title compounds displayed potent HDAC inhibitory activity. In particular, IF5 and IF6 exhibited significant enzymatic inhibitory activities, with IC50 values of 0.73 ± 0.08 and 0.57 ± 0.16 μM, respectively. Furthermore, these compounds showed moderate antiproliferative activity against human cancer cells. Especially, IF6 displayed promising profile as an antitumor candidate with IC50 value of 3.91 ± 0.97 μM against HeLa cells. The results indicated that these isoferulic acid derivatives could serve as promising lead compounds for further optimization.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / toxicity
  • Binding Sites
  • Catalytic Domain
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cinnamates / chemical synthesis
  • Cinnamates / chemistry*
  • Cinnamates / toxicity
  • Drug Design*
  • HeLa Cells
  • Histone Deacetylase Inhibitors / chemical synthesis
  • Histone Deacetylase Inhibitors / chemistry*
  • Histone Deacetylase Inhibitors / toxicity
  • Histone Deacetylases / chemistry*
  • Histone Deacetylases / metabolism
  • Humans
  • Molecular Docking Simulation

Substances

  • Antineoplastic Agents
  • Cinnamates
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases
  • isoferulic acid