萘甲酰胺衍生物TW918的合成及体外活性考察

合成一系列萘甲酰胺衍生物,初步筛选出先导化合物TW918,测定其对肿瘤细胞的活性影响,考察其与激酶分子EGFR的结合性及对EGFR蛋白表达的影响.TW918结构经¹H-NMR,¹³C-NMR和HR-MS表征确证.实验结果表明:TW918对四种肿瘤细胞均有一定的抑制活性,但对正常细胞的影响较小;分子对接显示TW918能以母核喹啉为头,深入占据到EGFR的活性口袋中,并与活性残基形成氢键,其最低自由结合能为-46.1 kJ·mol^-1;TW918能以剂量依赖性方式明显抑制四种肿瘤细胞中EGFR蛋白的表达.

Synthesis and In Vitro Activity of Naphthamide Derivatives T W9 1 8

To synthesize a series of naphthamide derivatives and screen out one lead compound TW918, this paper studys its anti-tumor activity in vitro, and investigats its ability to bind with kinase and the effect on the expression of EGFR protein. ¹H-NMR, ¹³C-NMR and HR-MS confirmed the structure of TW918. The results of MTT assay showed that TW918 had certain inhibitory effects against four types of tumor cells, but had less effects on normal cells. Molecular docking revealed that TW918 could make use of the quinoline as head to occupy the activity pocket of EGFR deeply, and form hydrogen bonds with the active residues of EGFR around it, whose lowest free binding energy was -46.1 kJ·mol^-1. Western Blot demonstrated that TW918 could inhibit the expression of EGFR in all four types of tumor cells in a dose-dependent manner significantly.