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目的设计合成一系列2-氰基-3,12-二氧代齐墩果烷-1,9(11)-二烯-28-酰胺类化合物,以期寻找活性更好的抗肿瘤化合物。方法以2-氰基-3,12-二氧代齐墩果烷-1,9(11)-二烯-28-羧酸(CDDO)为先导化合物,将CDDO的17位羧基通过连接基团与各种氨基化合物进行偶联制得目标化合物;采用MTT法测试偶联物对乳腺癌MDA-MB-468细胞的增殖抑制活性。结果与结论目标化合物的结构经IR、MS及1H-NMR谱确证,合成的10个化合物对乳腺癌MDA-MB-468细胞显示出不同程度的增殖抑制活性,明显优于先导化合物CDDO,其中,化合物2i、2j的活性最强(IC50值分别为1.12、1.37μmol·L-1)。构效关系研究发现,二胺偶联物的活性最好,氨基酸和正丙醇胺偶联物的活性次之,而芳胺偶联物的活性较弱,化合物2i和2j值得进一步研究。
Aim To design and synthesize a series of 2-cyano-3,12-dioxo-oleanane-1,9 (11) -dien-28-amides with the aim of finding more active anti-tumor compounds. Methods The 2-cyano-3,12-dioxo-oleanodine-1,9 (11) -diene-28-carboxylic acid (CDDO) was used as the lead compound. With a variety of amino compounds were coupled to obtain the target compound; MTT assay was used to test the proliferation of breast cancer MDA-MB-468 cells inhibitory activity. RESULTS AND CONCLUSIONS The structures of the target compounds were confirmed by IR, MS and 1H-NMR spectra. The 10 compounds showed different degrees of proliferation inhibitory activity on breast cancer MDA-MB-468 cells, which was significantly better than the lead compound CDDO. Among them, Compound 2i, 2j activity of the strongest (IC50 values were 1.12,1.37μmol·L-1). The structure-activity relationship study found that diamine conjugate activity is the best, amino acid and n-propanolamine conjugate activity followed, while the aromatic amine conjugate activity is weak, compounds 2i and 2j worth further study.