药学学报, 2013, 48(12): 1800-1806
引用本文:
毕重文, 张彩霞, 李阳彪, 赵午莉, 邵荣光, 梅林, 宋丹青. 环化小檗碱类似物的合成及其抗肿瘤活性研究[J]. 药学学报, 2013, 48(12): 1800-1806.
BI Chong-wen, ZHANG Cai-xia, LI Yang-biao, ZHAO Wu-li, SHAO Rong-guang, MEI Lin, SONG Dan-qing. Synthesis and structure-activity relationship of cycloberberine as anti-cancer agent[J]. Acta Pharmaceutica Sinica, 2013, 48(12): 1800-1806.

环化小檗碱类似物的合成及其抗肿瘤活性研究
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
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
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6c6e6g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。
关键词:    环化小檗碱      抗肿瘤      构效关系      耐药      拓扑异构酶     
Synthesis and structure-activity relationship of cycloberberine as anti-cancer agent
BI Chong-wen1, ZHANG Cai-xia1, LI Yang-biao1, ZHAO Wu-li1, SHAO Rong-guang1, MEI Lin2, SONG Dan-qing1
1. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China;
2. Qingdao Municipal Hospital, Qingdao 266011, China
Abstract:
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.
Key words:    cycloberberine    anti-cancer    structure-activity relationship    drug-resistance    topoisomerase   
收稿日期: 2013-07-16
基金项目: 中央级公益性科研院所基本科研业务专项(4010202).
通讯作者: 梅林, 宋丹青
Email: linmeiml@yahoo.com;songdanqingsdq@sina.com
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