岩白菜素衍生物合成方法及抗肿瘤活性评价

Synthesis and anti-tumour activity evaluation of bergenin derivatives

目的合成岩白菜素的衍生物,并评价其抗肿瘤活性。方法以天然植物鬼灯檠中分离得到的岩白菜素为原料,首先合成炔烃中间体,然后通过Click反应在其分子结构中引入三氮唑基团;运用甲基噻唑基四唑法检测制备的各种衍生物对胃癌MGC-803细胞、食管癌EC9706细胞、黑色素瘤B16细胞的体外抗肿瘤活性。结果制备出8种衍生物,大多衍生物对3种肿瘤细胞株有一定的细胞毒活性。其中衍生物4对食管癌EC9706细胞有很强的细胞毒活性,其半数抑制浓度(IC50)为(6. 2±0. 7)μmol·L^-1,优于阳性对照物氟尿嘧啶IC50值(6. 3±0. 1)μmol·L^-1。结论建立了操作简便的岩白菜素衍生物合成方法,为此类化合物抗肿瘤药物筛选奠定了实验基础。

Objective To synthesized bergenin derivatives and evaluated their antitumor activity. Methods The bergenin extracted from Rodgersia aesculifolia Batal. was used as raw material for the synthesis of the alkyne intermediate,and the triazolium group was introduced into its molecular structure by Click reaction. Their antitumor activities of the bergenin derivatives against gastric cancer cells MGC-803,esophageal cancer cells EC9706 and melanoma cells B16 in vitro was detected by methylthiazolidyl tetrazole method. Results A total of 8 derivatives were obtained from bergenin,and most of the compounds showed potent antitumor activity to above three tumor cells. The compound 4 showed strong cytotoxic activity to esophageal cancer cells EC9706,and its half maximal inhibitory concentration(IC50) value was(6. 2 ± 0. 7)μmol·L-1,which was better than the positive control substance fluorouracil [IC50 was(6. 3 ± 0. 1)μmol·L^-1]. Conclusion A simple method for the synthesis of bergenin derivatives was established,which laid the experimental foundation for the screening of antitumor drugs.