Publication

Reactivity of isothiazolones and isothiazolone-1-oxides in the inhibition of the PCAF histone acetyltransferase

Ghizzoni, M., Haisma, H. J. & Dekker, F. J., Dec-2009, In : European Journal of Medicinal Chemistry. 44, 12, p. 4855-4861 7 p.

Research output: Contribution to journalArticleAcademicpeer-review

Development of small molecule inhibitors of the histone acetyltransferase p300/CBP associated factor (PCAF) is relevant for oncology. The inhibition of the enzyme PCAF and proliferation of the cancer cell line HEP G2 by a series of 5-chloroisothiazolones was compared to a series of 5-chloroisothiazolone-1-oxides. The PCAF inhibitory potency of 5-chloroisothiazolones and 5-chloroisothiazolone-1-oxides is influenced by substitution in the 4-position. A study on the reactivity of the HAT inhibitors towards thiols and thiolates indicates that 5-chloroisothiazolones reacted quickly with propane-1-thiolate to provide many products, whereas 5-chloroisothiazolone-1-oxides provide only one defined product. Growth inhibition studies indicate that 5-chloroisothiazolones inhibit proliferation of HEP G2 cells at concentrations between 8.6 and 24 mu M, whereas 5-chloroisothiazolone-1-oxides required higher concentrations or showed no inhibition. (C) 2009 Elsevier Masson SAS. All rights reserved.

Original languageEnglish
Pages (from-to)4855-4861
Number of pages7
JournalEuropean Journal of Medicinal Chemistry
Volume44
Issue number12
Publication statusPublished - Dec-2009

    Keywords

  • Histone acetyltransferase, PCAF, Isothiazolone, Isothiazolone-1-oxide, Epigenetics, Antitumour, SIMILARITY CLUSTERING PSSC, LYSINE ACETYLTRANSFERASES, ACETYLATION, SUPERFAMILY, DERIVATIVES, DISEASES, DESIGN, P300, HATS

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