Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1397875 | European Journal of Medicinal Chemistry | 2009 | 7 Pages |
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 μM, whereas 5-chloroisothiazolone-1-oxides required higher concentrations or showed no inhibition.
Graphical abstractThe inhibition of the histone acetyltransferase p300/CBP associated factor (PCAF) and proliferation of HEP G2 cells by a series of 5-chloroisothiazolones and 5-chloroisothiazolone-1-oxides has been studied. Figure optionsDownload full-size imageDownload as PowerPoint slide