Structure-activity relationship and enzyme kinetic studies on 4-aryl-1H-1,2,3-triazoles as indoleamine 2,3-dioxygenase (IDO) inhibitors

Eur J Med Chem. 2011 Nov;46(11):5680-7. doi: 10.1016/j.ejmech.2011.08.044. Epub 2011 Sep 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • Cell Proliferation / drug effects
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • HEK293 Cells
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / chemistry
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism*
  • Inhibitory Concentration 50
  • Kinetics
  • Models, Molecular
  • Structure-Activity Relationship
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • Triazoles / chemical synthesis
  • Triazoles / chemistry*
  • Triazoles / pharmacology*

Substances

  • Enzyme Inhibitors
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Triazoles