title: Design, synthesis and biological evaluation of pyrazolyl-nitroimidazole derivatives as potential EGFR/HER-2 kinase inhibitors.
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 0.13μM to 128.06μM in four tumor cell lines. Among them, compound 5c exhibited remarkable inhibitory activity against EGFR/HER-2 tyrosine kinase with IC50 value of 0.26μM/0.51μM, respectively, comparable to the positive control erlotinib (IC50=0.41μM for HER-2 and IC50=0.20μM for EGFR) and lapatinib (IC50=0.54μM for HER-2 and IC50=0.28μM 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.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 163 Xianlin Road, Nanjing 210023, People's Republic of China.
authors.forename: Xiang-Xiang
authors.initials: XX
authors.lastname: Tao
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 163 Xianlin Road, Nanjing 210023, People's Republic of China.
authors.forename: Yong-Tao
authors.initials: YT
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 163 Xianlin Road, Nanjing 210023, People's Republic of China.
authors.forename: Long-Wang
authors.initials: LW
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 163 Xianlin Road, Nanjing 210023, People's Republic of China.
authors.forename: Dan-Jie
authors.initials: DJ
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 163 Xianlin Road, Nanjing 210023, People's Republic of China.
authors.forename: Meng-Ru
authors.initials: MR
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 163 Xianlin Road, Nanjing 210023, People's Republic of China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 163 Xianlin Road, Nanjing 210023, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 163 Xianlin Road, Nanjing 210023, People's Republic of China. Electronic address: zhuhl@nju.edu.cn.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D009593:Nitroimidazoles / Q000737:chemistry* / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; D009593:Nitroimidazoles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human; C508053:ERBB2 protein, human
keywords: Anticancer activity; Cytotoxicity; EGFR/HER-2 inhibitors; Molecular docking and QSAR; Pyrazole-nitroimidazole derivatives