二肽类膦酸酯衍生物的合成与抗肿瘤活性

为了寻找抗肿瘤活性化合物,以前期研究的含一个氨基酸结构单元的膦酸酯衍生物为基础,设计合成了15个二肽类膦酸酯衍生物(Ⅲa-Ⅲo)。采用溴化噻唑蓝四氮唑(MTT)法进行体外抗肿瘤活性测试。结果表明:该类化合物对人肺癌细胞(A-549)、人胃癌细胞(SGC-7901)和人食管癌细胞(EC-109)有潜在增殖抑制作用。其中,化合物Ⅲf对A-549和EC-109的半数抑制浓度(IC 50)分别为(6.9±1.2)和(6.3±1.0)μmol/L,化合物Ⅲn对SGC-7901和EC-109的IC 50分别为(6.7±1.0)和(6.1±1.0)μmol/L,与对照药顺铂接近。

Synthesis and Antitumor Activity of Phosphonate Derivatives Containing Dipeptide

In order to find antitumor compounds,fifteen dipeptide phosphonate derivatives(Ⅲa-Ⅲo)were designed and synthesized based on the phosphonate derivatives containing one amino acid fragment.Their antitumor activities in vitro were evaluated by the MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide)assay.The results show that the compounds inhibit the proliferation of the tumor cells.Among the active compounds,compound Ⅲf has better inhibition effect on A-549(human lung cancer cells)and EC-109(human esophageal cancer cells)growth with the half maximal inhibitory concentration(IC50)values of(6.9±1.2)and(6.3±1.0)μmol/L,respectively,and compound Ⅲn shows more potent antitumor activities against SGC-7901(human gastric cancer cells)and EC-109 with the IC50 values of(6.7±1.0)and(6.1±1.0)μmol/L,respectively,close to that of cisplatin.