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根据拼合原理,以天然产物齐墩果酸和熊果酸作为先导化合物,通过丁二酸连接片段,在C-28位分别导入哌嗪、N-甲基哌嗪及吗啉片段,共设计、合成了12种未见文献报道的齐墩果酸和熊果酸衍生物.利用IR、1H NMR、13C NMR和HRMS等波谱技术对所合成的目标化合物进行了结构表征,并采用3-(4,5-二甲基-2-噻唑)-2,5-二苯基溴化四氮唑噻唑蓝(MTT)法观察其对癌细胞的抑制作用,结果表明化合物OA-4、OA-7、OA-8a、OA-8b、UA-4、UA-7、UA-8a和UA-8b对人乳腺癌细胞(MCF-7)、人宫颈癌细胞(Hela)和人肺腺癌细胞(A549)的抑制作用远优于先导化合物齐墩果酸和熊果酸,且OA-4,OA-7,UA-4和UA-7与阳性对照物Gefitinib的IC50值相当.
According to the principle of splitting, oleanolic acid and ursolic acid, the natural products, were used as the lead compounds, piperazine, N-methylpiperazine and morpholine fragments were introduced into the C-28 position through the succinic acid linker fragment, Twelve novel derivatives of oleanolic acid and ursolic acid were synthesized and characterized by IR, 1H NMR, 13C NMR and HRMS.The structures of the target compounds were characterized by 3- (4 5-dimethyl-2-thiazolyl) -2,5-diphenyl tetrazolium tetrazolium bromide (MTT) method was used to observe its inhibitory effect on cancer cells. The results showed that the compounds OA-4, OA- Human breast cancer cells (MCF-7), human cervical cancer cells (Hela) and human lung adenocarcinoma cells (A549) were treated with OA-8a, OA-8b, UA-4, UA-7, UA-8a and UA- Is much better than the leading compounds oleanolic acid and ursolic acid, and the IC50 values of OA-4, OA-7, UA-4 and UA-7 are comparable to those of the positive control Gefitinib.