Walton James W, Cross Jasmine M, Riedel Tina, Dyson Paul J
Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK.
Org Biomol Chem. 2017 Nov 7;15(43):9186-9190. doi: 10.1039/c7ob02339a.
A series of potent histone deacetylase inhibitors is presented that incorporate alkyl or perfluorinated alkyl chains. Several new compounds show greater in vitro antiproliferative activity than the clinically approved inhibitor, SAHA. Furthermore, the new compounds show up to 5-fold greater activity against cancer cells than healthy cells. This selectivity is in contrast to SAHA, which is more active against the healthy cell line than the cancer cell line tested. Finally, we report an increase in activity for SAHA under mild hyperthermia, indicating that it could be an interesting candidate to use in combination with thermal therapy.
本文介绍了一系列含有烷基或全氟烷基链的强效组蛋白脱乙酰酶抑制剂。几种新化合物在体外显示出比临床批准的抑制剂SAHA更强的抗增殖活性。此外,新化合物对癌细胞的活性比对健康细胞高5倍。这种选择性与SAHA相反,SAHA对测试的健康细胞系比对癌细胞系更具活性。最后,我们报道了在轻度热疗条件下SAHA活性的增加,这表明它可能是与热疗联合使用的一个有趣候选药物。