Mechanistic studies on the selective inhibition of cyclooxygenase-2 by indanone derivatives

Biochem Pharmacol. 1996 Feb 9;51(3):285-90. doi: 10.1016/0006-2952(95)02170-1.


The cyclooxygenase step in the conversion of arachidonic acid is a key point in the biosynthesis of prostanoids, managed by two enzymatic isoforms. In the following study we focused on the mechanism of the inhibitory action of CGP 28238 and structurally-related indanone derivatives using purified enzymes. Consistent with our earlier studies on cell systems, CGP 28238 revealed selective inhibition of cyclooxygenase-2. The process affects the bisoxygenase subunit time-dependently, and is reversible in the early phase of inhibition. From structure-activity relationships, we propose the formation of a Schiff base between the oxo-groups of CGP 28238 and an amino group at the active site providing additional binding forces for an effective inhibition of cyclooxygenase-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acid / metabolism
  • Cells, Cultured
  • Cyclooxygenase Inhibitors / pharmacology*
  • Humans
  • Indans / pharmacology*
  • Isoenzymes / isolation & purification
  • Isoenzymes / metabolism
  • Prostaglandin-Endoperoxide Synthases / isolation & purification
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Prostaglandins / biosynthesis
  • Rats
  • Structure-Activity Relationship


  • Cyclooxygenase Inhibitors
  • Indans
  • Isoenzymes
  • Prostaglandins
  • Arachidonic Acid
  • indacrinone
  • Prostaglandin-Endoperoxide Synthases
  • flosulide