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目的设计合成4-(甲基苯胺基)-3-氰基喹啉类衍生物,并对其体外抗肿瘤活性进行初步评价。方法以氰乙酸乙酯为起始原料,经多步反应合成目标化合物。采用MTT法,以吉非替尼(gefitinib)为阳性对照药,以A549、HT-29和MDA-MB-231为测试细胞株对目标化合物的抗肿瘤活性进行评价。结果合成了18个新化合物,其结构经1H-NMR、MS和IR确认。体外活性测试结果显示,多数化合物可在较低浓度抑制肿瘤细胞增殖,其中的Ⅶ2、Ⅶ3、Ⅶ6、Ⅶ12、Ⅶ13、Ⅶ15和Ⅶ16共7个化合物有显著的抗增殖活性,优于阳性对照药gefitinib。结论体外活性实验表明,4-(甲基苯胺基)-3-氰基喹啉类衍生物作为新型的酪氨酸激酶抑制剂,其构效关系值得进一步研究。
Objective To design and synthesize 4- (methylanilino) -3-cyanoquinoline derivatives and evaluate the antitumor activity in vitro. Methods Ethyl cyanoacetate was used as the starting material to synthesize the target compound by multi-step reaction. The anti-tumor activity of the target compounds against A549, HT-29 and MDA-MB-231 cells was evaluated by MTT assay with gefitinib as positive control. Results Eighteen new compounds were synthesized and their structures were confirmed by 1H-NMR, MS and IR. In vitro activity test results showed that most compounds could inhibit the proliferation of tumor cells at a lower concentration. Among them, seven compounds of Ⅶ 2, Ⅶ 3, Ⅶ 6, Ⅶ 12, Ⅶ 13, Ⅶ 15 and Ⅶ 16 had significant antiproliferative activity, which was better than the positive control gefitinib . Conclusion In vitro activity experiments show that the structure-activity relationship of 4- (methylanilino) -3-cyanoquinoline derivatives is worthy of further study as a novel tyrosine kinase inhibitor.