Synthesis, molecular docking and evaluation of thiazolyl-pyrazoline derivatives containing benzodioxole as potential anticancer agents

A series of novel thiazolyl-pyrazoline derivatives containing benzodioxole (C1–C20) have been designed and synthesized. Among of the synthesized compounds, 2-(5-(benzo[d][1,3]dioxol-5-yl)-3-(4-bromophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-4-(4-bromophenyl)thiazole (C6) displayed the most potent inhibito...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2013-01, Vol.21 (2), p.448-455
Main Authors: Wang, Hai-Hong, Qiu, Ke-Ming, Cui, Hong-En, Yang, Yu-Shun, Yin-Luo, Xing, Man, Qiu, Xiao-Yang, Bai, Li-Fei, Zhu, Hai-Liang
Format: Article
Language:English
Subjects:
antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - toxicity
Antitumor agents
Benzodioxole
Benzodioxoles - chemistry
Binding Sites
Cell Line, Tumor
Cell Proliferation - drug effects
chemistry
HER-2
Humans
inhibitory concentration 50
MCF-7 Cells
Molecular Docking Simulation
Protein Kinase Inhibitors - chemical synthesis
Protein Kinase Inhibitors - chemistry
Protein Kinase Inhibitors - toxicity
Protein Structure, Tertiary
Pyrazoles - chemical synthesis
Pyrazoles - chemistry
Pyrazoles - toxicity
Pyrazoline
Receptor, ErbB-2 - antagonists & inhibitors
Receptor, ErbB-2 - metabolism
Structure-Activity Relationship
Thiazole
Thiazoles - chemistry
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Summary:A series of novel thiazolyl-pyrazoline derivatives containing benzodioxole (C1–C20) have been designed and synthesized. Among of the synthesized compounds, 2-(5-(benzo[d][1,3]dioxol-5-yl)-3-(4-bromophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-4-(4-bromophenyl)thiazole (C6) displayed the most potent inhibitory activity for HER-2 (IC50=0.18μM for HER-2). Antiproliferative assay results indicated that compound C6 owned high antiproliferative activity against MCF-7 and B16-F10 in vitro, with IC50 value of 0.09 and 0.12μM, respectively, being comparable with the positive control Erlotinib. Docking simulation was further performed to determine the probable binding model. Based on the preliminary results, compound C6 with potent inhibitory activity in tumor growth would be a potential anticancer agent. A series of novel thiazolyl-pyrazoline derivatives containing benzodioxole (C1–C20) have been designed and synthesized. Among of the synthesized compounds, 2-(5-(benzo[d][1,3]dioxol-5-yl)-3-(4-bromophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-4-(4-bromophenyl)thiazole (C6) displayed the most potent inhibitory activity for HER-2 (IC50=0.18μM for HER-2). Antiproliferative assay results indicated that compound C6 owned high antiproliferative activity against MCF-7 and B16-F10 in vitro, with IC50 value of 0.09 and 0.12μM, respectively, being comparable with the positive control Erlotinib. Docking simulation was further performed to determine the probable binding model. Based on the preliminary results, compound C6 with potent inhibitory activity in tumor growth would be a potential anticancer agent.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2012.11.020