熊果酸衍生物的合成及抗肿瘤血管生成活性  

Synthesis and Anti-angiogenesis Activities of Ursolic Acid Derivatives

作　　者：张文娟[1,2] 陈少鹏[1] 陆鑫[1] 周国春[1,2] 

机构地区：[1]中国科学院广州生物医药与健康研究院,广州510663 [2]中国科学院研究生院,北京100049

出　　处：《高等学校化学学报》2010年第11期2206-2217,共12页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:30973621);中国科学院知识创新项目(批准号:KSCX-2-YW-R-22)资助

摘　　要：对熊果酸C28位与C3位进行结构修饰得到了24个衍生物,并利用1H NMR,13C NMR,MS及HR-MS对这些化合物进行了结构表征.进一步通过MTT法,以内皮细胞HUVEC为主要模型,研究了24个衍生物抗肿瘤血管生成的活性,同时以A549,Bel-7402及MCF-7细胞为模型研究了上述衍生物对肿瘤细胞的抑制活性.研究结果表明,与熊果酸相比,化合物5,9,12e和14e对HUVEC细胞有较好的选择性,化合物12a和13h比熊果酸的抗肿瘤血管生成活性略高,因此通过适当改变熊果酸C28位的结构可以提高其对内皮细胞HUVEC的选择性,增强抗肿瘤血管生成活性.本文结果表明,熊果酸及其衍生物是潜在的具有抗肿瘤血管生成作用的先导化合物,通过有效的结构优化可能得到新型的抗肿瘤血管生成的化合物.Twenty-four derivatives of ursolic acid modified at C3 and C28 were designed and synthesized for the investigation of the structure-activity relationship of ursolic acid（1） against angiogenesis.All the com-pounds were characterized by 1H NMR,13C NMR,MS and HR-MS.HUVEC was used as an angiogenesis tar-get cell and A549,Bel-7402 and MCF-7 were as cancer target cells and the antiproliferative activity was as-sayed by MTT method.The results show that compounds 5,9,12e and 14e possess the selectively antiprolif-erative activity of HUVEC,meanwhile,compounds 12a and 13h are more active than compound 1 against the proliferation of HUVEC.Therefore,it is possible that more potent and selective angiogenesis inhibitors of ur-solic acid derivatives could be discovered by suitable modification at C28 position of ursolic acid.These data suggest that ursolic acid and its derivatives represent a promising lead structural core to discover a new class of antiangiogenesis agents.

关 键 词：熊果酸 衍生物 抗肿瘤血管生成 抑制细胞增殖 

分 类 号：O624.13[理学—有机化学]