Department of Pharmaceutical Gene Modulation, Faculty of Mathematics and Natural Sciences, University of Groningen, Anthonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Eur J Med Chem. 2009 Dec;44(12):4855-61. doi: 10.1016/j.ejmech.2009.07.025. Epub 2009 Aug 3.
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 microM, whereas 5-chloroisothiazolone-1-oxides required higher concentrations or showed no inhibition.
小分子抑制剂的开发组蛋白乙酰转移酶 p300/CBP 相关因子 （PCAF） 是相关的肿瘤学。该酶 PCAF 和癌细胞系 Hep G2 的增殖的抑制作用的一系列 5-氯异噻唑酮 1-氧化物进行了比较了一系列的 5-氯异噻唑酮。5-氯异噻唑酮和 5-氯异噻唑酮-1-氧化物的 PCAF 抑制效力受取代在 4 位的影响。对 HAT 抑制剂的巯基和硫醇盐的反应性的研究表明，5-氯异噻唑酮与丙烷-1-硫醇盐迅速反应，提供许多产物，而 5-氯异噻唑酮-1-氧化物只提供一个明确的产物。生长抑制研究表明，5-氯异噻唑酮抑制 Hep G2 细胞增殖的浓度之间的 8.6 和 24 μ M，而 5-氯异噻唑酮-1-氧化物需要更高的浓度或不显示抑制作用。
