Synthesis, biological evaluation, and molecular docking studies of 1,3,4-oxadiazole derivatives possessing 1,4-benzodioxan moiety as potential anticancer agents

被引：105
作者：
Zhang, Xiao-Min [1 ]
Qiu, Min [1 ]
Sun, Juan [1 ]
Zhang, Yan-Bin [1 ]
Yang, Yu-Shun [1 ]
Wang, Xiao-Liang [1 ]
Tang, Jian-Feng [1 ]
Zhu, Hai-Liang [1 ]
机构：
[1] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2011年 / 19卷 / 21期
基金：
美国国家科学基金会;
关键词：
Synthesis; 1,3,4-Oxadiazole derivatives; Molecular docking; Antitumor activity; Telomerase inhibitor; ANTIINFLAMMATORY ACTIVITY; ANTITUMOR;
D O I：
10.1016/j.bmc.2011.08.013
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
In present study, a series of new 1,3,4-oxadiazole derivatives containing 1,4-benzodioxan moiety (6a-6s) as potential telomerase inhibitors were synthesized. The bioassay tests demonstrated that compounds 6k, 6l, 6m, 6n and 6s exhibited broad-spectrum antitumor activity with IC50 concentration range from 7.21 mu M to 25.87 mu M against the four cancer cell lines, HEPG2, HELA, SW1116 and BGC823. Moreover, all the title compounds were assayed for telomerase inhibition using the TRAP-PCR-ELISA assay. The results showed compound 6k possessed the most potent telomerase activity (IC50 = 1.27 +/- 0.05 mu M). Docking simulation was performed to position compound 6k into the active site of telomerase (3DU6) to determine the probable binding model. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码：6518 / 6524
页数：7
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