膦酸酯糖苷衍生物的合成与抗肿瘤活性

Synthesis and Antitumor Activity of Glycoside Drivatives Containing Posphonate

摘要:

以α-羟基膦酸酯和溴代单糖为中间体，碱性离子液体[Bmim]OH为催化剂，微波辅助，以79.6%-84.1%的收率合成了系列膦酸酯糖苷化合物（Ⅲa-Ⅲf），经IR, 1HNMR, 13CNMR确认了产物结构。采用溴化噻唑蓝四氮唑 (MTT) 法进行了体外抗肿瘤活性测试。结果表明：该类化合物对人胃癌细胞 (SGC-7901)和人肺癌细胞 (A-549)有增殖抑制作用，其中，含葡萄糖基片段的目标物Ⅲa、Ⅲb对SGC-7901有较优的增殖抑制作用，IC50分别为12.9±0.9μmol/L、14.3±1.1μmol/L；含半乳糖基片段的目标物Ⅲc、Ⅲd对A-549有较显著活性，IC50分别为15.9±0.9μmol/L、14.2±1.3μmol/L。

Abstract:

A series of title compounds(Ⅲa-Ⅲf) were synthesized via microwave-assisted by the yield of 79.6%-84.1%, with α-hydroxyphosphonate and bromo mono-saccharide intermediates as raw materials, alkaline ionic liquid [Bmim]OH as catalyst. Their structures were confirmed by IR, 1HNMR and 13CNMR, and their antiproliferative activities were evaluated in some tumor cell lines by MTT assay. Prelimi-nary results in bioactivity tests indicated that some title compounds exhibited better activity. Among them, compounds Ⅲa, Ⅲb containing the glucose group had better inhibition effect against SGC-7901 with IC50 values of 12.9 ± 0.9μmol/L, 14.3± 1.1μmol/L respectively, compounds Ⅲc, Ⅲd containing the galactose fragments showed remarkable activities against A-549 with IC50 values of 15.9 ± 0.9μmol/L and 14.2 ± 1.3 μmol/L respectively.