淫羊藿素衍生物的合成及其体外抗肝癌活性研究

Synthesis of Icaritin Derivative and Their Anti-hepatocarcinoma Activity in Vitro

目的:合成一种淫羊藿素葡萄糖衍生物,提高淫羊藿素溶解度及体外抗癌活性。方法:通过化学方法合成淫羊霍素葡萄糖衍生物(IS);以核磁共振谱、质谱和HPLC进行结构鉴定和纯度检测,考察其在不同溶剂中的溶解度;MTT法检测IS对肝癌细胞HepG2、SMMC7721和正常肝细胞LO2的生长抑制作用。结果:成功得到了一种淫羊藿素葡萄糖衍生物IS,与淫羊藿素相比,溶解度得到了有效提高,细胞毒性实验结果表明,对HepG2细胞,淫羊藿素的IC50值在48、72 h时分别为:20.59±2.82μmol/L和16.05±1.27μmol/L,IS分别为:15.05±1.32μmol/L和7.69±0.04μmol/L;对SMMC7721细胞,淫羊藿素在48、72 h时的IC50值分别为:23.24±1.02μmol/L和14.96±0.66μmol/L,IS在72 h的IC50值为9.57±1.21μmol/L,在48 h时IS没无明显的抑制效果;IS对LO2细胞平均活率为67.96%(给药浓度100μmol/L)。结论:成功合成淫羊藿素葡萄糖衍生物IS,显著改善淫羊藿素溶解度,与原料药相比,IS对HepG2及SMMC7721细胞具有更强的生长抑制作用,对正常肝细胞毒性低,具有较大的研究价值。

Objective:To synthesize a glucose derivative of icariin(IS),in order to improve its solubility and anticancer activity in vitro.Methods:IS was synthesized by chemical method;NMR,MS and HPLC were used for structure identification and purity detection,and the solubility of the compounds in different solvents was investigated.The growth inhibition of IS on hepatocellular carcinoma cells HepG2,SMMC7721 and normal hepatocytes LO2 cells was detected by MTT assay.Results:A glucose derivative of icariin IS was successfully obtained.Compared with icaritin,the solubility was effectively increased.The cytotoxicity results showed that for HepG2 cells,the IC50 values of icaritin were 20.59±2.82 μmol/L,16.05±1.27 μmol/L at 48 and 72 h,respectively,and the IC50 values of IS were 15.05±1.32 μmol/L and 7.69±0.04 μmol/L;For SMMC7721 cells,the IC50 values of icaritin were 23.24±1.02 μmol/L and 14.96±0.66 μmol/L at 48 and 72 h,respectively.The IC50 value of IS at 72 h was 9.57±1.21 μmol/L,and there was no obvious inhibitory effect of IS at 48 h.For normal hepatocytes cells LO2,the average viability rate was 67.96%(administration concentration was 100 μmol/L).Conclusion:A icaritin glucose derivative IS is successfully synthesized,which significantly improves the solubility of icaritin.It displays obvious growth inhibition effect on HepG2 and SMMC7721 cells compared with the icaritin,and has little cytotoxicity to normal liver cells.It has great research value.