Zhou Ping, Huang Linsheng, Zhou Jie, Jiang Bin, Zhao Yanmei, Deng Xuehua, Zhao Qin, Li Fei
Department of Hepatopancreatobiliary Surgery, Taihe Hospital, Hubei University of Medicine, Hubei, China.
School of Pharmaceutical Sciences, Hubei University of Medicine, Hubei, China.
Bioorg Med Chem Lett. 2017 Sep 1;27(17):4185-4189. doi: 10.1016/j.bmcl.2017.07.005. Epub 2017 Jul 5.
A series of novel 4(1H)-quinolone derivatives was synthesized and evaluated for antiproliferative activity in vitro. The results showed that these compounds exhibited more potent antiproliferative effect against a panel of human tumorcelllines than the lead compound 7-chloro-4(1H)-quinolone 1. Compound 7e was found to be the most potent antiproliferative agent and to exhibit selective cytotoxic activity against HepG2 cell lines with IC value lower than 1.0μM. Annexin V/FITC-PI assay showed that compound 7e induced apoptosis in HepG2 cells with a dose-dependent manner. Western blotting analysis indicated that compound 7e induced cell cycle arrest in G2/M phase by p53-depedent pathway.
合成了一系列新型4(1H)-喹诺酮衍生物，并对其体外抗增殖活性进行了评估。结果表明，这些化合物对一组人肿瘤细胞系表现出比先导化合物7-氯-4(1H)-喹诺酮1更强的抗增殖作用。发现化合物7e是最有效的抗增殖剂，对HepG2细胞系表现出选择性细胞毒活性，IC值低于1.0μM。膜联蛋白V/异硫氰酸荧光素-碘化丙啶检测表明，化合物7e以剂量依赖方式诱导HepG2细胞凋亡。蛋白质印迹分析表明，化合物7e通过p53依赖途径诱导细胞周期阻滞在G2/M期。
