Design, synthesis and biological evaluation of pyrazolyl-nitroimidazole derivatives as potential EGFR/HER-2 kinase inhibitors. Issue 2 (15th January 2016)

• Record Type: Journal Article
• Authors: Tao, Xiang-Xiang; Duan, Yong-Tao; Chen, Long-Wang; Tang, Dan-Jie; Yang, Meng-Ru; Wang, Peng-Fei; Xu, Chen; Zhu, Hai-Liang
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 2(2016)
• Page Start: 677
• Page End: 683
• Publication Date: 2016-01-15
• Subjects: Pyrazole-nitroimidazole derivatives -- EGFR/HER-2 inhibitors -- Anticancer activity -- Cytotoxicity -- Molecular docking and QSAR; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.11.040
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: 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 μM to 128.06 μM in four tumor cell lines. Among them, compound5c exhibited remarkable inhibitory activity against EGFR/HER-2 tyrosine kinase with IC50 value of 0.26 μM/0.51 μM, respectively, comparable to the positive control erlotinib (IC50 = 0.41 μM for HER-2 and IC50 = 0.20 μM for EGFR) and lapatinib (IC50 = 0.54 μM for HER-2 and IC50 = 0.28 μM 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.