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

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.