海洋天然产物brefeldin A的衍生物制备及细胞毒活性评价(英文)

Preparation and cytotoxicity evaluation of marinenatural product brefeldin A derivatives

目的 对海洋天然产物brefeldin A(1)的双键以及羟基进行修饰,半合成9个衍生物2~10并考察其对人非小细胞肺癌细胞系A549细胞的抑制活性。方法 利用MTT法,用人非小细胞肺癌细胞系A549对衍生物(2~10)进行细胞毒活性测定。结果 通过对化合物1的结构引入硫原子、乙酰化修饰分别得到衍生物2~7和8~10,所有衍生物均可在1μmol/L以下抑制A549细胞生长,其中衍生物8和9活性较为显著,半抑制浓度(IC50)分别为422和127 nmol/L,可作为潜在的抗癌先导化合物。

Objective To modify the double bonds and hydroxyl groups of marine natural product brefeldin A(1),derivatives 2~10 were prepared and their inhibitory activities against lung adenocarcinoma epithelial A549 were evaluated.Methods The cytotoxic activities of all derivatives(2~10)against lung adenocarcinoma epithelial A549 were evaluated using MTT assay.Conclusion Derivatives 2~7 and 8~10 were designed and synthesized via introducing sulfur atoms and acetylation into the structure of 1,respectively.All derivatives can inhibit the growth of A549 cells below 1μmol/L,among which derivatives 5 and 9 exhibited significant activities,with IC50 values of 40 nM and 98 nM respectively,which can be used as potential anticancer lead compounds.