Abstract
Two series of thiazolidinone derivatives designing for potential EGFR and HER-2 kinase inhibitors have been discovered. Some of them exhibited significant EGFR and HER-2 inhibitory activity. Compound 2-(2-(5-bromo-2-hydroxybenzylidene)hydrazinyl)thiazol-4(5H)-one (12) displayed the most potent inhibitory activity (IC(50)=0.09 microM for EGFR and IC(50)=0.42 microM for HER-2), comparable to the positive control erlotinib. Docking simulation was performed to position compound 12 into the EGFR active site to determine the probable binding model. Antiproliferative assay results indicating that some of the thiazolidinone derivatives own high antiproliferative activity against MCF-7. Compound 12 with potent inhibitory activity in tumor growth inhibition would be a potential anticancer agent.
Copyright (c) 2009 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / pharmacology*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Drug Screening Assays, Antitumor
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ErbB Receptors / antagonists & inhibitors*
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ErbB Receptors / chemistry
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ErbB Receptors / metabolism
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Humans
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Models, Molecular
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Neoplasms / drug therapy
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Protein Binding
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology
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Receptor, ErbB-2 / antagonists & inhibitors*
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Receptor, ErbB-2 / metabolism
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Structure-Activity Relationship
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Thiazolidines / chemical synthesis
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Thiazolidines / chemistry*
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Thiazolidines / pharmacology*
Substances
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Antineoplastic Agents
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Protein Kinase Inhibitors
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Thiazolidines
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ErbB Receptors
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Receptor, ErbB-2