熊果酸衍生物的合成、表征及其对癌细胞的抑制活性  

Synthesis,Characterization and Anti-tumor Activity of Ursolic Acid Derivatives

作　　者：林凤屏[1] 邵敬伟[1] 杜华东[1] 代永超[1] 王涛 

机构地区：[1]福州大学化学化工学院,福州350108 [2]郑州博赛生物技术股份有限公司

出　　处：《应用化学》2010年第8期893-898,共6页Chinese Journal of Applied Chemistry

基　　金：福建省科技厅青年人才创新基金(2007F0347);福建省教育厅A类科技基金(JA08004)资助项目

摘　　要：以熊果酸为母体化合物,对其3-OH和17-COOH进行结构修饰,设计合成了9个熊果酸衍生物,其结构经IR、1HNMR和MS测试技术确证;噻唑蓝(MTT)比色法考察了所合成衍生物对体外人肝癌细胞HepG2培养增殖的抑制作用,结果显示受试衍生物均对细胞增殖有一定抑制作用,且呈剂量依赖性,其中衍生物9的抑制作用最强;衍生物9与细胞作用24h后,经Hoechst33342/PI双染色,倒置荧光显微镜下观察,出现细胞凋亡所具有的高蓝色/低红色荧光图;流式细胞术检测细胞周期发现:细胞被阻滞于S期,且阻滞作用随药物浓度的增加而增强。Structural modifications on 3-OH and 17-COOH were performed with ursolic acid as the starting compound. Nine compounds were synthesized and their structures were confirmed by IR,^1H NMR and MS. Cell growth inhibitory effects of the derivatives against human hepato carcinoma cell HepG2 were evaluated by MTT assay. The results demonstrate that all the tested compounds exhibited certain anti-tumor activities in vitro and showed a dose-dependent manner. Derivative 9 had the best anti-cancer activity. Cell apoptosis changes were observed by Hoechst 33342 /PI fluorescent stain after derivative 9 interacted with cell for 24 h. The dark blue /light red fluorescence images were taken by a laser scanning confocal microscope. Cell cycles were analyzed by flow cytometry that the cells were blocked in the S phase,and the effects were enhanced gradually with the increment of concentration.

关 键 词：熊果酸 衍生物 合成 抗癌活性 

分 类 号：O629[理学—有机化学]