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

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。

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.