Improved inhibition of the histone acetyltransferase PCAF by an anacardic acid derivative |
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| Authors: | Massimo Ghizzoni André Boltjes Chris de Graaf Hidde J. Haisma Frank J. Dekker |
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| Affiliation: | 1. Department of Pharmaceutical Gene Modulation, Groningen Research Institute of Pharmacy, Anthonius Deusinglaan 1, 9713 AV Groningen, The Netherlands;2. Leiden/Amsterdam Center for Drug Research (LACDR), Division of Medicinal Chemistry, Department of Pharmacochemistry, Faculty of Exact Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands |
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| 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. |
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