摘要
本研究设计合成了一组全新结构骨架的环化小檗碱(CBBR)类衍生物并对其抗肿瘤活性进行了评价,其中化合物6c、6e和6g对人肝癌HepG2细胞表现出较强的抗肿瘤活性,IC50值分别为176、123和91 nmol·L 1。尤其对阿霉素耐药的人乳腺癌MCF-7细胞也显示较好的抑制作用。初步作用机制显示,化合物6g阻滞肝癌HepG2细胞周期于G2/M期;在0.1 mg·mL 1时对DNA拓扑异构酶I(Top I)显示较强的抑制活性。研究结果为将此类化合物发展成一类新型抗肿瘤化合物奠定基础。
A series of cycloberberine derivatives were designed, synthesized and evaluated for their anti-cancer activities in vitro. Among these analogs, compounds 6c, 6e and 6g showed strong inhibition on human HepG2 cells. They afforded a potent effect against DOX-resistant MCF-7 breast cells as well. The primary mechanism showed that cell cycle was blocked at G2/M phase of HepG2 cells treated with 6g using flow cytometry assay. It significantly inhibited the activity of DNA Top I at the concentration of 0.1 mg .mL-1. Our results provided a basis for the development of this kind of compounds as novel anti-cancer agents.
出处
《药学学报》
CAS
CSCD
北大核心
2013年第12期1800-1806,共7页
Acta Pharmaceutica Sinica
基金
中央级公益性科研院所基本科研业务专项(4010202)
关键词
环化小檗碱
抗肿瘤
构效关系
耐药
拓扑异构酶
cycloberberine
anti-cancer
structure-activity relationship
drug-resistance
topoisomerase
