Synthesis, biological evaluation and docking study of 3-aroyl-1-(4-sulfamoylphenyl)thiourea derivatives as 15-lipoxygenase inhibitors

Eur J Med Chem. 2014 Jul 23:82:308-13. doi: 10.1016/j.ejmech.2014.05.054. Epub 2014 May 24.

Abstract

A series of 3-aroyl-1-(4-sulfamoylphenyl)thiourea derivatives containing sulfonamide moiety were designed and synthesized as 15-lipoxygenase (15-LOX) inhibitors. Most synthesized compounds showed potent activity against soybean 15-LOX with IC50 values less than 25 μM. The most potent compound 4c (3-methylbenzoyl derivative) with IC50 value of 1.8 μM was 10-fold more potent than quercetin. Interestingly, compound 4c also showed the highest antioxidant activity, as determined by ferric reducing antioxidant power (FRAP) assay. Its capacity for reducing ferric ion was more than ascorbic acid. The viability assay of the selected compound 4c against oxidative stress-induced cell death in differentiated PC12 cells revealed that compound 4c significantly protected neurons against cell death in low concentrations.

Keywords: 15-Lipoxygenase; Antioxidant activity; Docking study; Enzyme inhibitors; Sulfonamides; Thiourea.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonate 15-Lipoxygenase / metabolism*
  • Cell Death / drug effects
  • Cell Differentiation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Glycine max / enzymology*
  • Hydrogen Peroxide / antagonists & inhibitors
  • Hydrogen Peroxide / pharmacology
  • Lipoxygenase Inhibitors / chemical synthesis
  • Lipoxygenase Inhibitors / chemistry
  • Lipoxygenase Inhibitors / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Oxidative Stress / drug effects
  • PC12 Cells
  • Rats
  • Structure-Activity Relationship

Substances

  • Lipoxygenase Inhibitors
  • Hydrogen Peroxide
  • Arachidonate 15-Lipoxygenase