Design, synthesis and biological evaluation of pyrazolyl-nitroimidazole derivatives as potential EGFR/HER-2 kinase inhibitors. 2016

Xiang-Xiang Tao, and Yong-Tao Duan, and Long-Wang Chen, and Dan-Jie Tang, and Meng-Ru Yang, and Peng-Fei Wang, and Chen Xu, and Hai-Liang Zhu
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 163 Xianlin Road, Nanjing 210023, People's Republic of China.

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.

UI MeSH Term Description Entries
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D009593 Nitroimidazoles IMIDAZOLES having a nitro moiety. Nitroimidazole
D011720 Pyrazoles Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D015195 Drug Design The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D047428 Protein Kinase Inhibitors Agents that inhibit PROTEIN KINASES. Protein Kinase Inhibitor,Inhibitor, Protein Kinase,Inhibitors, Protein Kinase,Kinase Inhibitor, Protein,Kinase Inhibitors, Protein
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D062105 Molecular Docking Simulation A computer simulation technique that is used to model the interaction between two molecules. Typically the docking simulation measures the interactions of a small molecule or ligand with a part of a larger molecule such as a protein. Molecular Docking,Molecular Docking Simulations,Molecular Docking Analysis,Analysis, Molecular Docking,Docking Analysis, Molecular,Docking Simulation, Molecular,Docking, Molecular,Molecular Docking Analyses,Molecular Dockings,Simulation, Molecular Docking

Related Publications

Xiang-Xiang Tao, and Yong-Tao Duan, and Long-Wang Chen, and Dan-Jie Tang, and Meng-Ru Yang, and Peng-Fei Wang, and Chen Xu, and Hai-Liang Zhu
March 2012, Bioorganic & medicinal chemistry,
Xiang-Xiang Tao, and Yong-Tao Duan, and Long-Wang Chen, and Dan-Jie Tang, and Meng-Ru Yang, and Peng-Fei Wang, and Chen Xu, and Hai-Liang Zhu
January 2010, Bioorganic & medicinal chemistry,
Xiang-Xiang Tao, and Yong-Tao Duan, and Long-Wang Chen, and Dan-Jie Tang, and Meng-Ru Yang, and Peng-Fei Wang, and Chen Xu, and Hai-Liang Zhu
August 2016, Molecules (Basel, Switzerland),
Xiang-Xiang Tao, and Yong-Tao Duan, and Long-Wang Chen, and Dan-Jie Tang, and Meng-Ru Yang, and Peng-Fei Wang, and Chen Xu, and Hai-Liang Zhu
February 2024, Bioorganic & medicinal chemistry letters,
Xiang-Xiang Tao, and Yong-Tao Duan, and Long-Wang Chen, and Dan-Jie Tang, and Meng-Ru Yang, and Peng-Fei Wang, and Chen Xu, and Hai-Liang Zhu
January 2023, Pharmaceuticals (Basel, Switzerland),
Xiang-Xiang Tao, and Yong-Tao Duan, and Long-Wang Chen, and Dan-Jie Tang, and Meng-Ru Yang, and Peng-Fei Wang, and Chen Xu, and Hai-Liang Zhu
January 2015, Anti-cancer agents in medicinal chemistry,
Xiang-Xiang Tao, and Yong-Tao Duan, and Long-Wang Chen, and Dan-Jie Tang, and Meng-Ru Yang, and Peng-Fei Wang, and Chen Xu, and Hai-Liang Zhu
August 2022, European journal of medicinal chemistry,
Xiang-Xiang Tao, and Yong-Tao Duan, and Long-Wang Chen, and Dan-Jie Tang, and Meng-Ru Yang, and Peng-Fei Wang, and Chen Xu, and Hai-Liang Zhu
November 2009, Bioorganic & medicinal chemistry letters,
Xiang-Xiang Tao, and Yong-Tao Duan, and Long-Wang Chen, and Dan-Jie Tang, and Meng-Ru Yang, and Peng-Fei Wang, and Chen Xu, and Hai-Liang Zhu
November 2012, Bioorganic & medicinal chemistry,
Xiang-Xiang Tao, and Yong-Tao Duan, and Long-Wang Chen, and Dan-Jie Tang, and Meng-Ru Yang, and Peng-Fei Wang, and Chen Xu, and Hai-Liang Zhu
April 2021, European journal of medicinal chemistry,
Copied contents to your clipboard!