(2-amino-phenyl)-amides of omega-substituted alkanoic acids as new histone deacetylase inhibitors

Bioorg Med Chem Lett. 2004 Jan 5;14(1):283-7. doi: 10.1016/j.bmcl.2003.08.083.

Abstract

A variety of omega-substituted alkanoic acid (2-amino-phenyl)-amides were designed and synthesized. These compounds were shown to inhibit recombinant human histone deacetylases (HDACs) with IC(50) values in the low micromolar range and induce hyperacetylation of histones in whole cells. They induced expression of p21WAF1/Cip1 and caused cell-cycle arrest in human cancer cells. Compounds in this class showed efficacy in human tumor xenograft models.

MeSH terms

  • Amides / chemistry*
  • Amides / pharmacology*
  • Cell Cycle / drug effects
  • Cell Cycle / physiology
  • Cell Line, Tumor
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Histone Deacetylase Inhibitors*
  • Histone Deacetylases / metabolism
  • Humans

Substances

  • Amides
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases