Design, synthesis and biological evaluation of 2-phenylquinoline-4-carboxamide derivatives as a new class of tubulin polymerization inhibitors
Design, synthesis and biological evaluation of 2-phenylquinoline-4-carboxamide derivatives as a new class of tubulin polymerization inhibitors
复制标题
作为一类新型微管蛋白聚合抑制剂的2-苯基喹啉-4-甲酰胺衍生物的设计、合成和生物学评价
DOI：
10.1016/j.bmc.2017.09.004
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发表时间：
2017
影响因子：
3.5
通讯作者：
Lin Jun
中科院分区：
文献类型：
--
作者：
Zhu Li;Luo Kaixiu;Li Ke;Jin Yi;Lin Jun
合成了一系列新的2-苯基喹啉-4-甲酰胺衍生物，表征并评价了其对5种癌细胞系Hela、SK-OV-3、HCT 116、A549和MDA-MB-468以及正常人胎肺成纤维细胞系MRC-5的抗增殖活性。其中化合物7 b对SK-OV-3和HCT 116细胞具有较强的体外细胞毒活性，IC 50值分别为0.5和0.2 μM。一般来说，抗增殖活性与秋水仙素结合位点的结合特性和对微管蛋白聚合的抑制作用相关。此外，免疫荧光和流式细胞术分析显示，所选化合物引起有丝分裂纺锤体组装的破坏和细胞周期的G2/M期阻滞，这与增殖抑制活性相关。分子对接分析证实了微管蛋白的秋水仙素结合位点与7的相互作用。这些结果表明这些化合物是有希望的微管蛋白聚合抑制剂，可有效治疗癌症。
A novel series of 2-phenylquinoline-4-carboxamide derivatives was synthesized, characterized and evaluated for its antiproliferative activity against five cancer cell lines, Hela, SK-OV-3, HCT116, A549 and MDA-MB-468, and a normal human fetal lung fibroblastic cell line, MRC-5. Among them, compound7bdisplayed potent cytotoxic activity in vitro against SK-OV-3 and HCT116 cell lines with IC50values of 0.5 and 0.2 μM, respectively. In general, the antiproliferative activity was correlated with the binding property of the colchicine binding site and inhibitory effect on tubulin polymerization. In addition, immunofluorescence and flow cytometry analysis revealed that selected compounds caused disruption of the mitotic spindle assembly and G2/M phase arrest of the cell cycle, which correlated with proliferation inhibitory activity. Molecular docking analysis demonstrated the interaction of7bat the colchicine binding site of tubulin. These results indicate these compounds are promising inhibitors of tubulin polymerization for the potent treatment of cancer.