化学
细胞毒性
赫拉
细胞凋亡
酰胺
A549电池
立体化学
顺铂
结构-活动关系
细胞培养
IC50型
铅化合物
细胞毒性T细胞
体外
组合化学
生物化学
化疗
外科
生物
医学
遗传学
作者
Fei Zhou,Gaorong Wu,Desheng Cai,Bing Xu,Mengmeng Yan,Tao Ma,Wenbo Guo,Wenxi Zhang,Xuemei Huang,Xiaohui Jia,Yuqin Yang,Feng Gao,Peng-Long Wang,Haimin Lei
标识
DOI:10.1016/j.ejmech.2019.06.029
摘要
Glycyrrhetinic acid (GA) had been the star anticancer lead compound and appealed to many scientists all over the world; however, its antitumor activity was not potent enough. To improve GA's cytoxicity and explore the effect of bonding mode on antitumor activity, 32 compounds including GA-OH series (GO, esters in C-3 position) and GA-NH2 series (GN, with amide linkages in C-3 position) had been designed and synthesized. All the compounds were screened for in vitro cytotoxicity against A549, HepG2, MCF-7, Hela and MDCK cell lines. As a result, all the de-protected (without Boc group) derivatives showed much stronger cytotoxic activity than GA, and surprisingly enough, all the GN series of the compounds were more potent than GO series against various tumor cells. Among them, the compound 26 (amide linkages in C-3 position) exhibited stronger antitumor activity against A549 cell line (IC50 = 2.109 ± 0.11 μM) than the positive drug cisplatin (IC50 = 9.001 ± 0.37 μM). Further studies indicated that compound 26 could induce A549 apoptosis via nuclei fragmentation. The detection of apoptosis and cell cycle analysis indicated that compound 26 could induce the early apoptosis and prevent A549 cells transition from S to G2 phase. Furthermore, the structure-activity relationships were briefly discussed. Among which, current study displayed amide linkages in C-3 position could effectively enhance GA cytotoxicity, providing a new modification strategy for further study.
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