Abstract
A series of 1,2,3-triazolylsalicylamide derivatives has been developed from the antiproliferative agent 7 and was evaluated for their Aurora kinase inhibitory activity. The novel 1,2,3-triazolylsalicylamide scaffold could be readily assembled by Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition, allowing rapid access to the structurally diverse analogues. The synthesized 1,2,3-triazolylsalicylamide derivatives revealed a significant Aurora kinase inhibitory activity. In particular, 8g inhibited Aurora A with IC50 values of 0.37μM. The critical role of phenolic -OH in the binding was confirmed by a molecular modeling study.
Keywords:
1,2,3-Triazole; Anticancer; Aurora kinase; Click chemistry; Library.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aurora Kinase A / antagonists & inhibitors*
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Aurora Kinase A / metabolism
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Aurora Kinase B / antagonists & inhibitors*
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Aurora Kinase B / metabolism
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Click Chemistry*
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Dose-Response Relationship, Drug
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Drug Discovery*
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Humans
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Molecular Docking Simulation
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Molecular Structure
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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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Salicylamides / chemical synthesis
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Salicylamides / chemistry
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Salicylamides / pharmacology*
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Structure-Activity Relationship
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Triazoles / chemical synthesis
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Triazoles / chemistry
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Triazoles / pharmacology*
Substances
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Protein Kinase Inhibitors
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Salicylamides
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Triazoles
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methyl 3-(5-(4-(3,5-dimethoxyphenyl)-1H-1,2,3-triazol-1-yl)-2-hydroxybenzamido)benzoate
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AURKA protein, human
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Aurora Kinase A
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Aurora Kinase B