Dekker Frank J, Ghizzoni Massimo, van der Meer Nanette, Wisastra Rosalina, Haisma Hidde J
Department of Therapeutic Gene Modulation, Faculty of Mathematics and Natural Sciences, University of Groningen, Anthonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Bioorg Med Chem. 2009 Jan 15;17(2):460-6. doi: 10.1016/j.bmc.2008.12.008. Epub 2008 Dec 13.
Small molecule HAT inhibitors are useful tools to unravel the role of histone acetyl transferases (HATs) in the cell and have relevance for oncology. We present a systematic investigation of the inhibition of the HAT p300/CBP Associated Factor (PCAF) by isothiazolones with different substitutions. 5-chloroisothiazolones proved to be the most potent inhibitors of PCAF. The growth inhibition of 4 different cell lines was studied and the growth of two cell lines (A2780 and HEK 293) was inhibited at micromolar concentrations by 5-chloroisothiazolones. Furthermore, the 5-chloroisothiazolone preservative Kathon CG that is used in cosmetics inhibited PCAF and the growth of cell lines A2780 and HEK 293, which indicates that this preservative should be applied with care.
小分子组蛋白乙酰转移酶（HAT）抑制剂是揭示组蛋白乙酰转移酶（HATs）在细胞中的作用的有用工具，并且与肿瘤学相关。我们对具有不同取代基的异噻唑啉酮对HAT p300/CBP相关因子（PCAF）的抑制作用进行了系统研究。5-氯异噻唑啉酮被证明是PCAF最有效的抑制剂。研究了5-氯异噻唑啉酮对4种不同细胞系的生长抑制作用，在微摩尔浓度下，它抑制了两种细胞系（A2780和HEK 293）的生长。此外，化妆品中使用的5-氯异噻唑啉酮防腐剂凯松CG抑制了PCAF以及细胞系A2780和HEK 293的生长，这表明该防腐剂应谨慎使用。
