Improved inhibition of the histone acetyltransferase PCAF by an anacardic acid derivative.
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.
Ghizzoni
Massimo
M
Department of Pharmaceutical Gene Modulation, Groningen Research Institute of Pharmacy, Groningen, The Netherlands.
Boltjes
André
A
Graaf
Chris de
Cd
Haisma
Hidde J
HJ
Dekker
Frank J
FJ
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
D048729:Anacardic Acids; D004791:Enzyme Inhibitors; C088115:anacardic acid; D051548:Histone Acetyltransferases