Design, synthesis and biological evaluation of novel nitroaromatic compounds as potent glutathione reductase inhibitors

Bioorg Med Chem Lett. 2011 Sep 15;21(18):5398-402. doi: 10.1016/j.bmcl.2011.07.002. Epub 2011 Jul 13.

Abstract

Discovery of GR inhibitors has become very popular recently due to antimalarial and anticancer activities. In this study, the synthesis and GR inhibitory capacities of novel nitroaromatic compounds (NCs) (1-3) were reported. Some commercially available molecules were also tested for comparison reasons. The novel NCs were obtained in high yields using simple chemical procedures and exhibited much potent inhibitory activities against GR at low micromolar concentrations with K(i) values ranging from 0.211 to 4.57 μM as compared with well-known agents. Inhibition mechanism was assessed as being due to occlusion of the active site entrance by means of the NCs. Molecular docking results have shown that docking poses of ligands are able to construct binding interactions with the essential amino acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemistry Techniques, Synthetic
  • Crystallography, X-Ray
  • Dinitrobenzenes / chemical synthesis
  • Dinitrobenzenes / chemistry
  • Dinitrobenzenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Glutathione Reductase / antagonists & inhibitors*
  • Glutathione Reductase / metabolism
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Dinitrobenzenes
  • Enzyme Inhibitors
  • Glutathione Reductase