Design, synthesis and biological evaluation of pyrazolyl-nitroimidazole derivatives as potential EGFR/HER-2 kinase inhibitors

被引：55

作者：

Tao, Xiang-Xiang ^{[1
]}

Duan, Yong-Tao ^{[1
]}

Chen, Long-Wang ^{[1
]}

Tang, Dan-Jie ^{[1
]}

Yang, Meng-Ru ^{[1
]}

Wang, Peng-Fei ^{[1
]}

Xu, Chen ^{[1
]}

Zhu, Hai-Liang ^{[1
]}

机构：

[1] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210023, Jiangsu, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 02期

关键词：

Pyrazole-nitroimidazole derivatives; EGFR/HER-2; inhibitors; Anticancer activity; Cytotoxicity; Molecular docking and QSAR; ANTITUMOR-ACTIVITY; TYROSINE KINASES; CANCER; IDENTIFICATION; MISONIDAZOLE; NUCLEOSIDES; METABOLISM; ETHERS; BREAST; EGFR;

D O I：

10.1016/j.bmcl.2015.11.040

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel pyrazole-nitroimidazole derivatives had been arranged and evaluated for their EGFR/HER-2 tyrosine kinase inhibitory activity as well as their antiproliferative properties on four kinds of cancer cell lines (MCF-7, Hela, HepG2, B16-F10). The bioassay results showed most of the designed compounds exhibited potential antiproliferation activity, with the IC50 values ranging from 0.13 mu M to 128.06 mu M in four tumor cell lines. Among them, compound 5c exhibited remarkable inhibitory activity against EGFR/HER-2 tyrosine kinase with IC50 value of 0.26 mu M/0.51 mu M, respectively, comparable to the positive control erlotinib (IC50 = 0.41 mu M for HER-2 and IC50 = 0.20 mu M for EGFR) and lapatinib (IC50 = 0.54 mu M for HER-2 and IC50 = 0.28 mu M for EGFR). Molecular modeling simulation studies were performed in order to predict the biological activity of the proposed compounds and activity relationship (SAR) of these pyrazole-nitroimidazole derivatives. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：677 / 683

页数：7

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