MEK小分子抑制剂的设计、合成与初步活性研究

Design,synthesis and evaluation of a novel MEK protein inhibitors

基于已报道的MEK小分子抑制剂,运用Autodock 4.2研究其与MEK蛋白的作用方式,并以此设计、合成10个全新小分子化合物,其结构经~1H NMR和^(13)C NMR确定,并采用MTT法进行了体外抗肿瘤活性研究。结果表明,所设计的化合物大多对MCF-7、PANC-1、SY5Y和A549四种肿瘤细胞株有较好的作用。其中,化合物4、6、7、8、10表现了较好的活性。

This study was conducted to design and synthetize highly efficient, specific, non-resistant small MEK inhibitors. Based on active small molecules which have been reported, we studied the action mode with MEK protein using Autodock 4.2, generated innovative and feasible design method, designed novel small MEK protein inhibitors with a reference to molecular modeling and docking. The anti-tumor activities of four kinds of cells including MCF-7, PANC-1, SY5Y, A549 were tested with MTT method in vitro. The structure of 10 new small molecules has been determined with 1H NMR and 13C NMR. The compounds 4, 6, 7, 8, 10 had high antitumor activities, the compounds 1, 3, 5 also showed good activity, and the compounds 2, 9 showed cell selectivity in killing tumor.