齐墩果酸喹喔啉衍生物的合成及抗肿瘤活性研究

Synthesis and Antitumor Activity of Quinoxaline Oleanolic Acid Derivatives

恶性肿瘤是当今社会最影响人类健康的疾病之一,而从天然植物中能够提取很多抑制癌症的天然药物.齐墩果酸是天然抗癌药物之一.为提高齐墩果酸的生物活性,以齐墩果酸为先导化合物,在其A环并4,5-二氯喹喔啉环,同时对C-28位羧基进行酰胺化结构修饰,设计合成了4个新型齐墩果酸A环衍生物,其结构经^(1)H-NMR、MS等确认.采用MTT法,选用人肺癌细胞(A549)和人胃癌细胞(SGC7901)对所得化合物进行初步的体外抗肿瘤活性测试.结果表明:所测化合物对A549、SGC7901肿瘤细胞的抑制作用均强于母体齐墩果酸,尤其是化合物Ⅰ4表现出较为显著的抗肿瘤活性,与已上市药物多柔比星活性相当,值得进一步研究.

Malignant tumor is one of the most important diseases affecting human health in today’s society,and many natural drugs to inhibit cancer can be extracted from natural plants.Oleanolic acid is one of the natural anticancer drugs.In order to improve the bioactivity of oleanolic acid,4 novel oligolic acid A-ring derivatives were designed and synthesized by amideating C-28 carboxyl groups with oligolic acid as the lead compound in A-ring and 4,5-dichloroquinoxaline ring,and their structures were confirmed by 1 H-NMR and MS.MTT assay was used to determine the antitumor activity of the compound in vitro by using human lung cancer cells(A549)and human gastric cancer cells(SGC7901).The results showed that the inhibitory effect of the tested compound on A549 and SGC7901 tumor cells was stronger than that of the mother oleanolic acid.In particular,compound I4 showed significant anti-tumor activity,which was similar to the activity of the marketed drug doxorubicin and worthy of further study.