Details

Autor(en) / Beteiligte

• Ghizzoni, Massimo
• Boltjes, André
• Graaf, Chris de
• Haisma, Hidde J.
• Dekker, Frank J.

Titel

Improved inhibition of the histone acetyltransferase PCAF by an anacardic acid derivative

Ist Teil von

• Bioorganic & medicinal chemistry, 2010-08, Vol.18 (16), p.5826-5834

Ort / Verlag

Amsterdam: Elsevier Ltd

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• Histone acetyltransferases (HATs) are potential novel drug targets for treatment of inflammation. We present the development of salicylate derivative 6d, which is a twofold improved inhibitor of PCAF HAT activity and histone acetylation in HEP G2 cells. 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.