Abstract
Previously, we have reported the design and synthesis of 4-aryl-1H-1,2,3-triazoles as inhibitors of indoleamine 2,3-dioxygenase (IDO), a promising therapeutic target of cancer. Here, we present the structure-activity relationship and enzyme kinetic studies on a series of 4-aryl-1H-1,2,3-triazoles. Three compounds (1, 6, 8) were found to possess more IDO inhibitory potency than the most commonly used 1-methyltryptophan. The results from the structure-activity relationship and molecular docking studies indicated that an electron-withdrawing group with low steric hindrance near the NH group of triazoles was necessary for the IDO inhibition.
Copyright © 2011 Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Catalytic Domain
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Cell Proliferation / drug effects
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology*
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HEK293 Cells
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Humans
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Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors*
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Indoleamine-Pyrrole 2,3,-Dioxygenase / chemistry
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Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism*
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Inhibitory Concentration 50
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Kinetics
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Models, Molecular
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Structure-Activity Relationship
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T-Lymphocytes / cytology
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T-Lymphocytes / drug effects
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Triazoles / chemical synthesis
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Triazoles / chemistry*
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Triazoles / pharmacology*
Substances
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Enzyme Inhibitors
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Indoleamine-Pyrrole 2,3,-Dioxygenase
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Triazoles