海洋天然产物geodin系列衍生物的细胞毒活性评价及构效关系初步研究

Cytotoxic evaluation and preliminary structure-activity relationships of the marine natural product geodin and its derivatives

目的评价具有grisan骨架的海洋天然产物geodin(1)及其衍生物(2~26)细胞毒活性,探究其初步构效关系。方法采用MTT法,用人非小细胞肺癌细胞系A549和人肝癌细胞系HepG2、Bel-7402对geodin(1)及其衍生物(2~26)进行了细胞毒活性评价。结果对geodin的4-OH修饰后得到的衍生物中,化合物2~4、6、7、9~18和20~25表现出强到中等程度的细胞毒活性,IC_(50)为0.81~4.78μmol/L。特别是化合物16,对A549和HepG2细胞表现出强效的细胞毒活性,其IC50分别为0.86、0.81μmol/L。结论化合物16是1种潜在的抗癌先导化合物。

Objective The cytotoxic activities of geodin(1),with the grisan skeleton isolated from marine fungus Aspergillus sp.,and its derivatives(2-26)were evaluated against three cancer cell lines.The preliminary structure-activity relationships were also discussed.Methods The cytotoxic activities of geodin(1)and its derivatives(2-26)against lung adenocarcinoma epithelial A549,hepatocellular carcinoma HepG2 and Bel-7402 cell lines were evaluated using MTT assay.Results Most of the 4-OH modified derivatives(2-4,6,7,9-18 and 20-25)of geodin(1)showed strong to moderate cytotoxic activities,with IC_(50) values of ranging from 0.81 to 4.78μmol/L.Especially,compound 16 exhibited strong cytotoxic activities against A549 and HepG2 cell lines with the ICso values of 0.86 and 0.81μmol/L,respectively.Conclusion Compound 16 is a potential anticancer lead compound.