齐墩果酸衍生物的合成及抗肿瘤活性研究

Synthesis and anti-tumor activity of oleanolic acid derivatives

摘要: 以天然产物齐墩果酸为起始原料,对其C-3 位羟基、C-12 位双键、C-28 位羧基进行结构改造,合成了13 个新的齐墩果酸衍生物.目标化合物结构经MS、¹H NMR 及元素分析确证.采用MTT 法,选用高表达人癌细胞(SGC7901、MCF-7 和A549)对目标化合物进行初步的体外抗肿瘤活性研究.结果表明,所测化合物对3种肿瘤细胞的抑制活性均明显强于齐墩果酸,其中化合物II₂和II₃对MCF-7和A549细胞表现出很强的抑制活性,明显高于已上市药物吉非替尼,值得进一步研究.

Abstract: Thirteen novel oleanolic acid (OA) derivatives were designed and synthesized with modification at positions of C-3, C-12 and C-28 of OA. Their structures were confirmed by MS, ¹H NMR and elemental analysis. Their in vitro cytotoxicities against various cancer cell lines (SGC7901, MCF-7 and A549) were evaluated by MTT assay. The results indicated that the tested derivatives were found to have stronger cell growth inhibitory activity than OA. Among them, compounds II₂ and II₃ showed more potent cytotoxicity on MCF-7 and A549 tumor cells than gefitinib (positive control). They are worthy to be studied further.