新型川芎嗪衍生物的合成及其抗癌活性研究  

Synthesis and anti-tumor activity evaluation of new ligustrazine derivatives

作　　者：王鹏龙[1] 徐昕[1] 李国梁[1] 褚福浩[1] 林锦璇[2] 绪扩[1] 周燊[1] 龚晏[1] 张宇忠[2] 李强[1] 雷海民[1] 

机构地区：[1]北京中医药大学中药学院,北京100102 [2]北京中医药大学基础医学院,北京100029

出　　处：《西北药学杂志》2014年第1期58-64,共7页Northwest Pharmaceutical Journal

基　　金：国家自然科学基金项目(No.81173519);北京中医药大学创新团队资助项目(2011-CXTD-15)

摘　　要：目的合成新型川芎嗪衍生物并对其抗癌活性和毒性进行评价。方法以中医经典方药中抗癌活性成分为原料,利用拼合原理,设计、合成川芎嗪衍生物,并采用四甲基偶氮唑蓝(MTT)法体外检测川芎嗪衍生物对Hela(人宫颈癌)细胞模型的抗癌活性和对正常细胞MDCK(犬肾上皮细胞)的毒性。结果获得4个未见报道的川芎嗪类新化合物,均经光谱方法鉴定了结构,其中化合物10和12能明显抑制Hela细胞的增殖,抗癌活性显著高于其合成前体;且对MDCK细胞的毒性明显小于顺铂。结论该结果进一步验证以拼合原理为指导,从经典方药中发现新型低毒抗癌先导化合物的研究思路是可行的。Obj ective To discover new anti-cancer agents with low toxicity,four new ligustrazine derivatives were synthesized by u-sing anti-tumor ingredients of the classic Chinese medicine as starting materials.Methods Our idea was enlightened by the combi-nation principle in drug discovery.The ligustrazine derivatives′anti-tumor activities were evaluated on the Hela human cancer cell line and their toxicities were evaluated on MDCK （Madin-Darby canine kidney）cell line.Results The structure of the intermediate and four new ligustrazine derivatives were characterized by 1 H NMR,13 C NMR and IR techniques.Compound 10 and 12 displayed more antiproliferative activities on Hela cell than their starting materials;moreover ligustrazine derivatives showed much lower toxicity on MDCK cell than DDP.Conclusion The results suggest that it is feasible to discover new anti-cancer lead compounds from classic formula via combination principle.

关 键 词：川芎嗪衍生物 拼合原理 抗肿瘤 先导化合物 

分 类 号：R914.2[医药卫生—药物化学]