New anacardic acid-inspired benzamides: histone lysine acetyltransferase activators

ChemMedChem. 2010 Sep 3;5(9):1530-40. doi: 10.1002/cmdc.201000158.

Abstract

A series of N-(4-cyano-3-trifluoromethyl-phenyl)-2-ethoxy-6-alkyl (and alkenyl) benzamides related to the anacardic acid derivative CTPB have been prepared from 2,6-dihydroxybenzoic acid with a Suzuki coupling and addition of the anion of 4-cyano-3-trifluoromethylphenylamine to a benzodioxinone as the key steps. In U937 cells, these analogues, in particular 7 c, 7 d, 7 f and 7 j, induced cell-cycle arrest in the G1 phase, caused apoptosis in about 20 % of the cells, and increased the acetylation levels of H3. These activities correlate with the enzymatic activation of histone lysine acetyltransferases (KATs): CBP and PCAF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Anacardic Acids / chemistry*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / toxicity
  • Apoptosis
  • Benzamides / chemical synthesis
  • Benzamides / chemistry*
  • Benzamides / toxicity
  • Cell Line, Tumor
  • G1 Phase
  • Histone Acetyltransferases / chemistry*
  • Histone Acetyltransferases / metabolism
  • Humans

Substances

  • Anacardic Acids
  • Antineoplastic Agents
  • Benzamides
  • anacardic acid
  • Histone Acetyltransferases