化学
吴茱萸碱
体内
药理学
效力
体外
癌症
IC50型
MTT法
癌细胞
对接(动物)
细胞凋亡
细胞生长
作者
Ziyi Liang,Fang Lei,Jiedan Deng,Honghua Zhang,Yuqing Wang,Junfang Li,Tao Shi,Xiaoyan Yang,Zhen Wang
标识
DOI:10.1016/j.ejmech.2021.113960
摘要
Abstract Gastric cancer represents a significant health burden worldwide. Previously, inspired by the traditional Chinese medicine Wu-Chu-Yu to treat the spleen and stomach system for thousands of years, we identified N14-phenyl substituted evodiamine derivatives as potential antitumor agents with favorable inhibition on Top1. Herein, structural optimization and structure-activity relationship studies (SARs) led us to discovering a highly active evodiamine derivative compound 6t against gastric cancer. Further anti-tumor mechanism studies revealed that compound 6t played as the inhibition of topoisomerase 1 (Top1), effectively induced apoptosis, obviously arrested the cell cycle at the G2/M phase, and significantly inhibited the migration and invasion of SGC-7901 and MGC-803 cell lines in a dose-dependent manner. Moreover, the compound 6t was low toxicity in vivo and exhibited excellent anti-tumor activity (TGI = 70.12%) in the MGC-803 xenograft models. In summary, compound 6t represents a promising candidate as a potential chemotherapeutic agent against gastric cancer.
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