Molecular modeling, synthesis and screening of some new 4-thiazolidinone derivatives with promising selective COX-2 inhibitory activity

Eur J Med Chem. 2012 Nov:57:59-64. doi: 10.1016/j.ejmech.2012.08.046. Epub 2012 Sep 7.

Abstract

In order to develop new selective cyclooxygenase-2 inhibitors, a series of novel 2-aryl-3-(4-sulfamoyl/methylsulfonylphenylamino)-4-thiazolidinones were designed. Molecular modeling studies with COX-2 enzyme were performed by using MOE program. The designed compounds with reasonable binding modes and high docking scores were synthesized. Their COX-1/COX-2 inhibitory activities were evaluated in vitro, using NS-398 and indomethacine as reference compounds. Compounds possessing methyl group (3d and 4d) on the phenyl ring exhibited highly COX-2 inhibitory selectivity and potency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Cyclooxygenase 1 / chemistry
  • Cyclooxygenase 2 / chemistry*
  • Cyclooxygenase 2 Inhibitors / chemical synthesis*
  • Cyclooxygenase 2 Inhibitors / chemistry
  • Humans
  • Indomethacin / chemistry
  • Magnetic Resonance Spectroscopy
  • Molecular Docking Simulation
  • Nitrobenzenes / chemistry
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / chemistry
  • Sheep
  • Structure-Activity Relationship
  • Sulfonamides / chemistry
  • Thiazolidines / chemical synthesis*
  • Thiazolidines / chemistry

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Nitrobenzenes
  • Recombinant Proteins
  • Sulfonamides
  • Thiazolidines
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Indomethacin