Synthesis and biological evaluation of N-substituted 3-oxo-1,2,3,4-tetrahydro-quinoxaline-6-carboxylic acid derivatives as tubulin polymerization inhibitors

被引：25

作者：

Qi, Jianguo ^{[1
]}

Dong, Haiyang ^{[1
]}

Huang, Jing ^{[1
]}

Zhang, Shufeng ^{[1
]}

Niu, Linqiang ^{[1
]}

Zhang, Yahong ^{[1
]}

Wang, Jianhong ^{[1
]}

机构：

[1] Henan Univ, Key Lab Nat Med & Immunoengn Henan Prov, Jinming Campus, Kaifeng 475004, Henan, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2018年 / 143卷

基金：

中国国家自然科学基金;

关键词：

Antiproliferative; Tubulin polymerization inhibitors; Cell cycle analysis; Cell apoptosis; 3-Oxo-1,2,3,4-tetrahydro-quinoxaline-6-carboxylic acid derivatives; VASCULAR DISRUPTING AGENTS; COMBRETASTATIN A-4; ANTITUMOR AGENTS; COLCHICINE SITE; ANTIPROLIFERATIVE AGENTS; CANCER THERAPEUTICS; TARGETING AGENTS; IN-VITRO; ANALOGS; BINDING;

D O I：

10.1016/j.ejmech.2017.08.018

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel N-substituted 3-oxo-1,2,3,4-tetrahydro-quinoxaline-6-carboxy-lic acid derivatives were synthesized and evaluated for their biological activities. Among all synthesized target compounds, 13d exhibited the most potent antiproliferative activity against HeLa, SMMC-7721, K562 cell line (IC50 = 0.126 mu M, 0.071 mu M, 0.164 mu M, respectively). Furthermore, compound 13d inhibited tubulin polymerization (IC50 = 3.97 mu M), arrested cell cycle at the G2/M phase and induced apoptosis. The binding mode at the colchicine binding site was also probed. These studies provided a new molecular scaffold for the further development of antitumor agents that target tubulin. (C) 2017 Elsevier Masson SAS. All rights reserved.

引用

页码：8 / 20

页数：13

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