二肽类膦酸酯衍生物的合成与抗肿瘤活性

doi:10.19894/j.issn.1000-0518.200183

摘要/Abstract

摘要： 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(IC₅₀)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IC₅₀分别为(6.7±1.0)和(6.1±1.0) μmol/L,与对照药顺铂接近。

关键词: 二肽, 膦酸酯, 抗肿瘤活性

Abstract: 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.

Key words: Dipeptide, Phosphonate, Antitumor activity

中图分类号:

O626.2

吴学姣, 苟光淋, 杨小兰, 杨家强. 二肽类膦酸酯衍生物的合成与抗肿瘤活性[J]. 应用化学, 2021, 38(1): 36-43.

WU Xue-Jiao, GOU Guang-Lin, YANG Xiao-Lan, YANG Jia-Qiang. Synthesis and Antitumor Activity of Phosphonate Derivatives Containing Dipeptide[J]. Chinese Journal of Applied Chemistry, 2021, 38(1): 36-43.

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