title: Improved inhibition of the histone acetyltransferase PCAF by an anacardic acid derivative.
abstract: Several lines of evidence indicate that histone acetyltransferases (HATs) are novel drug targets for treatment of diseases like, for example, cancer and inflammation. The natural product anacardic acid is a starting point for development of small molecule inhibitors of the histone acetyltransferase (HAT) p300/CBP associated factor (PCAF). In order to optimize the inhibitory potency, a binding model for PCAF inhibition by anacardic acid was proposed and new anacardic acid derivatives were designed. Ten new derivatives were synthesized using a novel synthetic route. One compound showed a twofold improved inhibitory potency for the PCAF HAT activity and a twofold improved inhibition of histone acetylation in HEP G2 cells.
authors.affiliation: Department of Pharmaceutical Gene Modulation, Groningen Research Institute of Pharmacy, Groningen, The Netherlands.
authors.forename: Massimo
authors.initials: M
authors.lastname: Ghizzoni
authors.forename: André
authors.initials: A
authors.lastname: Boltjes
authors.forename: Chris de
authors.initials: Cd
authors.lastname: Graaf
authors.forename: Hidde J
authors.initials: HJ
authors.lastname: Haisma
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Dekker
mesh_terms: D048729:Anacardic Acids / Q000737:chemistry* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D056945:Hep G2 Cells; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008958:Models, Molecular
chemical_list: D048729:Anacardic Acids; D004791:Enzyme Inhibitors; C088115:anacardic acid; D051548:Histone Acetyltransferases