新型熊果酸喹啉衍生物抗肿瘤活性研究

Study on Anti-Tumor Activity of New Ursolic Acid Quinoline Derivatives

原料为五环三萜类天然产物熊果酸,合成新型熊果酸喹啉衍生物。使用元素分析法、ESI-MS、13CNMR等,分析1,3,4-噁二唑衍生物4a-4f,以及熊果酸喹啉酰肼衍生物3a-3f。采用MTT法,对4a-4f、3a-3f进行测试,分析对三种肿瘤细胞株的增殖抑制活性。结果显示,对三种肿瘤细胞株,包括SMMC-77213、HeL、MDA-MB-231,3a-3c都有明显的抑制活性。比对照依托泊苷更强,对SMMC-77213、HeL、MDA-MB-231的IC50值,分别是17.49~19.43μmol/L、0.84~1.19μμmol/L、1.17~1.85μμmol/L。根据抗肿瘤活性结果显示,喹啉基引入熊果酸分子中,羧基修饰为1,3,4-噁二唑基、酰肼基,抗肿瘤活性能够明显增强,酰肼的衍生物为侧链,相比噁二唑的衍生物活性更佳。因此,能够进一步优化熊果酸结构,提升抗肿瘤活性。

In this paper,a new quinoline derivative of ursolic acid was synthesized from ursolic acid,a natural product of pentacyclic triterpenoids.Elemental analysis,ESI-MS and 13C NMR were used to analyze the derivatives 4a-4f of 1,3,4-oxadiazole and 3a-3f of quinolinyl hydrazide ursolic acid.MTT assay was used to test 4a-4f and 3a-3f,and to analyze their proliferation inhibition activities.The results showed that SMMC-77213,HeL,MDA-MB-231 and 3a-3c all had obvious inhibitory activity.The IC50 values of SMMC-77213,HeL and MDA-MB-231 were 17.49-19.43 ugM,0.84-1.19 ugM and 1.17-1.85 ugM,respectively.According to the results of anti-tumor activity,quinoline group was introduced into ursolic acid molecule,and carboxyl group was modified to 1,3,4-oxadiazole group and hydrazide group.The anti-tumor activity of quinoline group was obviously enhanced.The derivative of hydrazide was side chain,and its activity was better than that of Oxadiazole derivative.Therefore,it can further optimize the structure of ursolic acid and enhance its anti-tumor activity.