积雪草酸A环开环衍生物的合成及体外抗肿瘤活性研究

摘要

目的:设计并合成积雪草酸A环、C-23位羟基以及C-28位羧基衍生物,并对其体外抗肿瘤活性进行测试.方法:以天然产物积雪草酸为先导化合物,经氧化、酰化等反应对其A环、C-23位羟基以及C-28位羧基进行结构修饰,合成2,3-二氧代-2,3-开环-23-羟基(乙酰基)-乌苏烷型-12-烯-28-酯类衍生物.结果:经MS及1H-NMR谱图解析得到确证.结论:采用MTT法,选用人癌细胞SGC-7901和A549对它们进行初步的体外抗肿瘤活性测试.目标化合物对2种细胞株的抑制率均明显高于母体化合物,且化合物g和k的抑制效果高于吉非替尼,值得进一步研究.%Objective:To design and synthesize asiatic acid (AA) derivatives modified in ring-A,C-23 and C-28,and study the anti-tumor activities in vitro.Methods:Asiatic acid was used as the leading compound to synthesize 2,3-oxo-des-A-23-hydroxyl (acetyl)-urs-12-ene-28-ester through structural modification at C-2,C-3,hydroxyl of C-23,and carboxyl of C-28 respectively.The anti-tumor activities of the synthesized compounds against SGC-7901 and A549 were evaluated by MTT assay.Results:The structures have been verified by MS and 1HNMR.Conclusion:The MTT assay indicated that these compounds showed more potent inhibitory activity on the tumor cells than that of the parent compound AA,and the inhibition rates of compound g and k were better than gefitinib.The derivatives are worthy to be studied further.