Ding Pan-Pan, Gao Man, Mao Bei-Bei, Cao Sheng-Li, Liu Cui-Huan, Yang Chao-Rui, Li Zhong-Feng, Liao Ji, Zhao Hongchang, Li Zheng, Li Jing, Wang Hailong, Xu Xingzhi
Department of Chemistry, Capital Normal University, Beijing, 100048, PR China.
Department of Chemistry, Capital Normal University, Beijing, 100048, PR China.
Eur J Med Chem. 2016 Jan 27;108:364-373. doi: 10.1016/j.ejmech.2015.11.044. Epub 2015 Nov 28.
A series of quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at the C2-position were synthesized and evaluated for their antiproliferative activities against A549, MCF-7, HeLa, HT29 and HCT-116 cell lines. Most of the synthesized compounds exhibited broad spectrum antitproliferative activity against five cell lines, of which 5c was the most potent against HT29 cell line with an IC50 value of 5.53 μM, inducing a G2/M phase arrest in HT29 cells. Treatment of HT29 cells with 5c resulted in BubR1 phosphorylation and an increase of mitotic index in a time-dependent manner. Furthermore, 5c promoted tubulin polymerization in vitro. These results demonstrate that quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at C2-position may be potentially novel antitumor agents targeting tubulin to activate the spindle assembly checkpoint.
合成了一系列在C2位带有二硫代氨基甲酸盐侧链的喹唑啉-4(3H)-酮衍生物，并评估了它们对A549、MCF-7、HeLa、HT29和HCT-116细胞系的抗增殖活性。大多数合成化合物对五种细胞系表现出广谱抗增殖活性，其中5c对HT29细胞系最有效，IC50值为5.53 μM，可诱导HT29细胞发生G2/M期阻滞。用5c处理HT29细胞导致BubR1磷酸化，并以时间依赖性方式增加有丝分裂指数。此外，5c在体外促进微管蛋白聚合。这些结果表明，在C2位带有二硫代氨基甲酸盐侧链的喹唑啉-4(3H)-酮衍生物可能是潜在的新型抗肿瘤药物，靶向微管蛋白以激活纺锤体组装检查点。
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