含膦酸酯的L-苯丙氨酸二肽衍生物合成与抗肿瘤作用

Synthesis and antitumor activity of L-phenylalanine dipeptide derivatives containing phosphonate backbones

摘要:

为了寻找抗肿瘤活性化合物，设计合成了9个含膦酸酯结构的L-苯丙氨酸二肽衍生物，经1H NMR 、13C NMR 和MS对合成的产物进行了结构确认。采用溴化噻唑蓝四氮唑 (MTT) 法对目标化合物进行了体外抗肿瘤活性测试。结果表明：部分目标物对所测肿瘤细胞有增殖抑制作用，呈现潜在的抗肿瘤活性。尤以Ⅲi最为突出，对人肺癌细胞(A549)和人食管癌细胞(EC-109)均有显著抑制作用，IC50分别为6.8±0.9 μ mol/L、7.0±1.2 μ mol/L，与对照药cisplatin接近。

Abstract:

In order to search for antitumor compounds, nine L-phenylalanine dipeptide derivatives containing phosphonate backbones were designed and synthesized. Their structures were confirmed by 1H NMR, 13C NMR and MS. These compounds were tested for their antitumor activities in vitro by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The results showed that some of the target compounds had inhibitory effect on the proliferation of the tumor cells and showed potential antitumor activity. Among them, espectively, compound Ⅲi showed remarkable activities against A-549 and EC-109 with IC50 values of 6.8 ± 0.9 μmol/L and 7.0 ± 1.2 μmol/L, respectively, which were close to cisplatin.