目的为了进一步提高小檗碱的抗肿瘤活性,对小檗碱进行了烷基化,为开发新抗肿瘤药物奠定基础。方法以盐酸小檗碱为起始原料,经格氏试剂烷基化及溴代反应,合成一系列8-烷基-13-溴代-盐酸小檗碱,经UV、IR1、H-NMR和元素分析进行结构鉴定。用四甲基偶氮唑盐(MTT)法观测产物对人肝癌细胞HepG2增殖能力的影响。结果 发现该细胞对目标产物的敏感性与碳链长度有很大关系,其中8-辛基-13-溴代盐酸小檗碱对该细胞的敏感性最强,在浓度为32μg/mL时抑制率为96.82%,IC50为3.33μg/mL。结论从IC50可知在8个碳原子以内,随着溴代小檗碱侧链的增长,抗癌活性增强。

Objective To study the antitumor activity of berberine which was alkylated based on the development of new antitumor drug.Methods The alkylation and bromination of berberine were performed with Grignard reagent and bromine respectively to give 8-alkyl-13-bromo-berberine derivatives in good to excellent yields.The chemical structures of the derivatives were identified by UV,IR,1H-NMR,and elemental analysis.The antiproliferative effect of the derivatives on human hepatoma cell line HepG2 was evaluated by MTT after 48 h incubation.Results The results showed that the length of carbon chain of the derivatives was highly correlated with the tumor cell sensitivity and 8-octyl-13-bromo-berberine showed the remarkable activity.Its inhibitory rate was 96.82% at the concentration of 32 μg/mL and IC50 was 3.33 μg/mL.Conclusion Known from IC50,the antitumor activity could be enhanced within eight carbon atoms as the bromide side chain extension.

重庆市重大科技专项资助项目(CSTC,2008AA5021);重庆市自然科学基金资助项目(CSTC,2008BB5257);重庆市科委攻关项目(CSTC,2010AC5007)