熊果酸衍生物的合成及其对H_2O_2损伤PC12细胞的保护作用  

Synthesis of Ursolic Acid Derivatives and Their Protective Effects on PC12 Cells against H_2O_2-induced Damage

作　　者：叶辉[1,2] 李齐激[2] 史亚男[2] 杨艳[2] 杨付梅[2] 杨小生 

机构地区：[1]遵义医学院,贵州遵义563099 [2]贵州省中国科学院天然产物重点实验室,贵州贵阳550002

出　　处：《山地农业生物学报》2015年第2期61-66,共6页Journal of Mountain Agriculture and Biology

基　　金：贵州省科技重大专项[2013-6006];贵州省科技创新人才团队建设项目[2013-4006]

摘　　要：目的设计、合成具有抗H2O2损伤PC12细胞活性的熊果酸(Ursolic Acid,UA)衍生物。方法通过苄基化、磺酰化、烯化等反应对熊果酸C1-3、C28位点进行修饰,合成系列1α,2α,3α-三羟基熊果酸及其衍生物;采用MTT法对目标产物的细胞毒性、H2O2损伤PC12细胞保护作用进行测试。结果合成1,2,3-三羟基熊果酸及其衍生物9个(7-15),MTT活性测试结果显示化合物10细胞毒性比UA小,浓度为1.0×10-5mol/L时,对H2O2损伤PC12细胞抑制率为13.10%;13、15无细胞毒性,化合物15对H2O2损伤PC12细胞的保护作用强于阳性对照维生素E,浓度为1.0×10-4mol/L时,抑制率为40.18%。结论 1α,2α,3α-三羟基熊果酸对H2O2损伤的PC12细胞具有一定的保护作用,尤其是C28位被二乙胺、二乙醇胺取代后活性明显增强。bjective of this paper was to design and synthetize the ursolic acid（UA） derivatives which protected PC 12 cells from injury of hydrogen peroxide （H2O2）.1 α,2α,3 α-trihydroxyurs-12-en-28-oic and its derivatives were synthesized by benzylation,methyl sulfonylations and olefination in the location of C1-3 and C28.The cytotoxicity and the protection of hydrogen peroxide （H2O2） injury to PC12 cells activity were measured by MTT assay.Nine 1α,2oα,3α-trihydroxyurs-12-en-28-oic derivatives （7-15） were synthesized,and compound 10 exhibited weaker cytotoxicity than UA.When the concentration was 1.0 × 10-5mol/L,the survival rates of PC12 cells was 13.10％.Compounds 13 and 15 had hardly any cytotoxicity,especially 15.the protection of hydrogen peroxide （H2O2） injury to PC12 cells activity was superior to the positive control （vitamin E）.,The survival rates was 40.18％ at the concentration of 1.0 × 10-4mol/L.1 α,2α,3 α-trihydroxyurs-12-en-28-oic have the protective effects on hydrogen peroxide （H2 O2） injury to PC12 cells activity,especially when the C28 was substituted by diethylamine and Diethanolamine,the protective effects on hydrogen peroxide （H2O2） injury to PC12 cells activity was enhanced obviously.

关 键 词：熊果酸 衍生物 保护作用 

分 类 号：Q26[生物学—细胞生物学]