拓扑替康
喜树碱
化学
细胞毒性
拓扑异构酶
体外
细胞凋亡
体内
细胞毒性T细胞
药理学
毒性
细胞周期
细胞培养
细胞周期检查点
生物化学
生物
化疗
生物技术
有机化学
遗传学
作者
Cheng‐Jie Yang,Bin Li,Zhijun Zhang,Jianmei Gao,Meijuan Wang,Xiao-Bo Zhao,Zi‐Long Song,Ying‐Qian Liu,Hu Li,Yuyuan Chen,Kuo‐Hsiung Lee,Susan L. Morris‐Natschke,Chuanrui Xu
标识
DOI:10.1016/j.ejmech.2019.111971
摘要
For the purpose of advancing our research on diverse C-20 decorated derivatives of camptothecin (CPT), 46 new CPT acylthiourea derivatives were synthesized and evaluated in vitro for their cytotoxicity. All the compounds showed promising in vitro cytotoxicity against six tumor cell lines (Hep3B, MCF7, A549, MDA-MB-231, KB and KB-vin). Out of them, compound c20 possesses remarkable in vitro cytotoxic activity and is more potent than topotecan. Mechanistically, c20 not only induces cell cycle arrest and cell apoptosis in A549 cells, but also inhibits Topo I activity in the cell and cell-free system in a manner similar to that of topotecan. In both xenograft and primary HCC mouse models, c20 displays significant in vivo anti-cancer activity and is more potent than topotecan. In addition, the acute toxicity assay showed that c20 has no apparent toxicity to mouse liver, kidney and hemopoietic system of the FVB/N mice. Take together, these results indicated that compound c20 could be a potential anti-cancer candidate for further clinical trial.
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