环化小檗碱类似物的合成及其抗肿瘤活性研究  

Synthesis and structure-activity relationship of cycloberberine as anti-cancer agent

作　　者：毕重文[1] 张彩霞[1] 李阳彪[1] 赵午莉[1] 邵荣光[1] 梅林[2] 宋丹青[1] 

机构地区：[1]中国医学科学院、北京协和医学院医药生物技术研究所,北京100050 [2]青岛市市立医院,山东青岛266011

出　　处：《药学学报》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)

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.

关 键 词：环化小檗碱 抗肿瘤 构效关系 耐药 拓扑异构酶 

分 类 号：R916[医药卫生—药学]