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

Ghizzoni, M., Boltjes, A., de Graaf, C., Haisma, H. J. & Dekker, F. J., 15-Aug-2010, In : Bioorganic & Medicinal Chemistry. 18, 16, p. 5826-5834 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

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. (C) 2010 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)5826-5834
Number of pages9
JournalBioorganic & Medicinal Chemistry
Volume18
Issue number16
Publication statusPublished - 15-Aug-2010

    Keywords

  • Anacardic acid, Histone acetyltransferase, p300/CBP associated factor (PCAF), Salicylate derivatives, Enzyme inhibition, GLOBAL GENE-EXPRESSION, CHROMATIN TRANSCRIPTION, ACETYLATION, REPRESSES, HATS, DISEASES, P300

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