化学
查尔酮
拓扑异构酶
细胞凋亡
膜联蛋白
立体化学
细胞毒性
MTT法
细胞毒性T细胞
顺铂
体外
生物化学
生物
遗传学
化疗
作者
Penghui Li,Hong Jiang,Wenjin Zhang,Yong-Lian Li,Min-Cong Zhao,Wei Zhou,Lanyue Zhang,Yadong Tang,Chang‐Zhi Dong,Zhi‐Shu Huang,Hui-Xiong Chen,Zhiyun Du
标识
DOI:10.1016/j.ejmech.2018.01.010
摘要
Novel topoisomerase II (Topo II) inhibitors have gained considerable interest for the development of anticancer agents. In this study, a series of carbazole derivatives containing chalcone analogs (CDCAs) were synthesized and investigated for their Topo II inhibition and cytotoxic activities. The results from Topo II mediated DNA relaxation assay showed that CDCAs could significantly inhibit the activity of Topo II, and the structure-activity relationship indicated the halogen substituent in phenyl ring play an important role in the activity. Further mechanism studies revealed that CDCAs function as non-intercalative Topo II catalytic inhibitors. Moreover, some CDCAs showed micromolar cytotoxic activities. The most potent compound 3h exhibited notable growth inhibition against four human cancer cell lines. Flow cytometric analysis revealed that compounds 3d and 3h arrested the HL-60 cells in sub G1 phase by induction of apoptosis. It was further confirmed by Annexin-V-FITC binding assay. Western blot analysis revealed that compound 3h induces apoptosis likely through the activation of caspase proteins.
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