Trisubstituted thiophene analogues of 1-thiazolyl-2-pyrazoline, super oxidase inhibitors and free radical scavengers

Bioorg Med Chem. 2013 Jan 1;21(1):365-72. doi: 10.1016/j.bmc.2012.09.060. Epub 2012 Nov 2.

Abstract

Xanthine oxidase (XO) generates superoxide anions and H(2)O(2) for the self-defence system of organism. Abnormal production of this superoxide's (reactive oxygen species) is responsible for a number of complications including inflammation, metabolic disorder, cellular aging, reperfusion damage, atherosclerosis and carcinogenesis. Series of novel trisubstituted thiophenyl-1-thiazolyl-2-pyrazoline libraries are synthesized containing 2,5-dichloro thiophene, 5-chloro-2-(benzylthio) thiophene and 5-chlorothiophene-2-sulphonamide, from chalcones in PEG-400 as green solvent. Superoxide (XO) inhibitory and free radical scavenging activities were also figured out with molecular modeling analysis, bearing in mind their possible future for super oxide inhibitor (Gout) therapeutics, compound 3k shows interesting superoxide inhibitory and free radical scavenger activity with IC(50)=6.2 μM, in comparison with allopurinol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biphenyl Compounds / antagonists & inhibitors
  • Biphenyl Compounds / metabolism
  • Free Radical Scavengers / chemical synthesis
  • Free Radical Scavengers / chemistry*
  • Free Radical Scavengers / pharmacology*
  • Green Chemistry Technology
  • Molecular Docking Simulation
  • Picrates / antagonists & inhibitors
  • Picrates / metabolism
  • Polyethylene Glycols / chemistry
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Superoxides / antagonists & inhibitors
  • Superoxides / metabolism
  • Thiophenes / chemical synthesis
  • Thiophenes / chemistry*
  • Thiophenes / pharmacology*
  • Xanthine Oxidase / antagonists & inhibitors*
  • Xanthine Oxidase / metabolism

Substances

  • Biphenyl Compounds
  • Free Radical Scavengers
  • Picrates
  • Reactive Oxygen Species
  • Thiophenes
  • Superoxides
  • Polyethylene Glycols
  • 1,1-diphenyl-2-picrylhydrazyl
  • Xanthine Oxidase