薯蓣皂苷元A环和F环的结构改造及其抗肿瘤活性初探  

Synthesis of diosgenin derivatives based on structure modification of its A and F ring and preliminary study of their anti-tumor activity

作　　者：廖鹏飞[1] 董江红[1] 范举正[1] 

机构地区：[1]四川大学华西药学院,四川成都610041

出　　处：《华西药学杂志》2013年第4期364-371,共8页West China Journal of Pharmaceutical Sciences

摘　　要：目的提高薯蓣皂苷元类衍生物的抗肿瘤活性以及进一步研究其构效关系。方法基于薯蓣皂苷元结构,运用Autodock 4.2进行对接设计,合成了一系列全新A环、F环结构改造的氨基酸酰胺,内酰胺杂环薯蓣皂苷元类衍生物。采用MTT法对人肝癌细胞HepG-2、人恶性黑色素瘤细胞A375和人肺癌细胞A549进行体外抗肿瘤活性实验。结果合成13个新化合物,结构经1HNMR、13CNMR确定,体外抗肿瘤活性结果表明化合物8～13具有一定活性。结论化合物8～13都具有一定的体外抗肿瘤活性,化合物13的药理学活性与阳性对照品紫杉醇活性相近。OBJECTIVE To improve the anti-tumor activities of diosgenin derivatives and further investigate their SAR.METHODS Based on the structure of diosgenin,designed and docked by Autodock 4.2,a series of new amino acid amide and lactam heterocylic diosgenin derivatives obtained by the modification of its A and F ring were synthesized.Their anti-tumor activities in vitro were tested on human hepatoma HepG-2 cells,human malignant melanoma A375 cells and human lung adenocarcinoma A549 cells by MTT assay.RESULTS 13 novel compounds were synthesized and their structures were characterized by 1HNMR and 13CNMR.Results of anti-tumor activities indicated that compounds 8-13 showed certain anti-tumor activities.CONCLUSION Compounds 8-13 had certain anti-tumor activities in vitro.Compound 13 had a similar pharmacological activity with Taxol.

关 键 词：薯蓣皂苷元衍生物 体外抗肿瘤活性 HEPG-2 

分 类 号：R914[医药卫生—药物化学]