含Schiff碱芳香氮芥香豆素衍生物的设计、合成及抗肿瘤增殖活性

Design, synthesis and anti-proliferative activity of novel coumarin derivatives linking Schiff base and aryl nitrogen mustard

摘要: 基于生物电子等排及活性单元拼接原理，将Schiff碱、芳香氮芥药效基团N，N-二（2-氯乙基）胺基拼接到香豆素结构中，设计合成了系列新型含Schiff碱芳香氮芥的香豆素衍生物（7a～7v），结构经¹H NMR、MS及元素分析确证。采用MTT法评价了化合物对HepG2、DU145及MCF7肿瘤细胞的抗增殖作用。结果表明，部分化合物对肿瘤细胞的增殖具有较好的抑制作用，其中化合物7c、7f、7g、7h和7q对DU145和MCF7的抑制作用优于或相当于阳性对照，值得进一步研究。

Abstract: To explore novel coumarin derivatives with more potent anti-proliferative activity, a series of novel compounds were designed and synthesized by linking Schiff base and N, N-bis (2-chloroethyl) amine pharmacophore of nitrogen mustards to the coumarin’s framework. Their structures were confirmed by ¹H NMR, MS and element analysis techniques. In vitro anti-proliferative activities were evaluated against HepG2, DU145 and MCF7 cell lines by the standard MTT assay. The results showed that some of the target compounds exhibited strong anti-proliferative activities against selected tumor cells, and compounds 7c, 7f, 7g, 7h and 7q were better than or equal to the activities of positive control, they deserved further development.