常春藤皂苷元衍生物的合成和抗肿瘤活性

Synthesis and Antitumor Activity of Hederagenin Derivatives

以常春藤皂苷元为先导化合物,设计并合成了三个系列的含有各种杂环的新型常春藤皂苷元衍生物,并利用1H NMR, ^(13)CNMR和HRMS对其结构进行了表征.通过噻唑蓝(MTT)方法评估了这些化合物对人非小细胞肺癌细胞(A549)、人乳腺癌细胞(MCF-7)、人结肠癌细胞(HCT116)、人结肠癌细胞(SW620)、人肝癌细胞(Hep G-2)和人肝癌细胞(BEL7402)的体外抗肿瘤活性.实验结果表明,(3β,4α)-3,23-二羟基齐墩果-12-烯-28-酸-[1-(4-硝基苯基)-1H-1,2,3-三唑-4-基]甲酯(A5)对HCT116细胞的抗增殖活性最强(IC50=2.05μmol/L).蛋白印迹实验表明,化合物A5可能通过NF-κB信号通路发挥其抗肿瘤活性.

Using hederagenin as lead compound, three series of novel hederagenin derivatives containing various heterocycles were designed and synthesized. Their structures were characterized by 1H NMR, ^(13)C NMR and HRMS. The in vitro antitumor activities of these compounds on human non-small cell lung cancer cells(A549), human breast cancer cells(MCF-7), human colon cancer cells(HCT116), human colon cancer cells(SW620), human hepatoma cells(HepG-2) and human hepatoma cells(BEL7402) were evaluated by thiazolyl blue(MTT) method. The experimental results showed that(3β,4α)-3,23-dihydroxyolean-12-ene-28-acid-(1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl) methyl ester(A5) had the strongest anti-proliferative activity(IC50=2.05 μmol/L) on HCT116 cells. Western blotting experiments showed that compound A5 may exert its antitumor activity through NF-κB signaling pathway.