藤黄酸-NO供体衍生物的合成及抗肿瘤活性研究

Synthesis and anti-tumor activity of NO-donating derivatives of gambogic acid

摘要: 目的:从藤黄酸及其衍生物中寻找一种有效的细胞凋亡诱导剂。方法:为了进一步发现潜在的抗肿瘤先导化合物,设计合成了8个新的藤黄酸-NO供体衍生物,并通过体外MTT法测定它们对HT-29,Bel-7402,BGC-823和A549细胞的抑制活性。结果:通过MTT法检测细胞,观察形态学变化,Annexin-V/PI双染色法证实藤黄酸结构中C35被羟基取代的化合物4能诱导SKOV3细胞凋亡。结论:化合物4具有显著的诱导细胞凋亡作用,有望成为抗癌新药物研发中的潜在先导化合物。

Abstract: AIM:To find a potent apoptosis inducer from gambogic acid and its derivatives.METHODS:Eight new NO-donating derivatives of gambogic acid were synthesized as potential anti-tumor lead compounds and their inhibitory activity on the HT-29,Bel-7402,BGC-823,and A549 cell lines were evaluated in vitro by the MTT assay.RESULTS:Among these compounds,4 with a hydroxyl group at C35 of the gambogic acid moiety was identified as a SKOV3 cell apoptosis inducer through the MTT cell assay,observations of morphological changes,and Annexin-V/PI double staining assay.CONCLUSION:Compound 4 showed significant effects in inducing apoptosis and might serve as a potential lead compound for the discovery of new anticancer drugs.