Cyclooxygenase-mediated prostaglandin biosynthesis pathways: Implications for anti-inflammatory drug development and therapeutic targeting

Abstract

Cyclooxygenase enzymes catalyze the rate-limiting step in prostaglandin biosynthesis, representing major targets for anti-inflammatory therapeutics. This research characterized COX-1 and COX-2 kinetics, inhibitor selectivity profiles, and downstream prostaglandin production in cellular models. Experiments at Cairo Institute of Technology from December 2023 to April 2025 employed recombinant enzymes and human monocyte-derived macrophages. Results demonstrated COX-2 showed 4.2-fold higher catalytic efficiency than COX-1 for arachidonic acid conversion. Selective COX-2 inhibitors achieved IC50 values of 0.024 μM compared to 8.7 μM for COX-1. Prostaglandin E2 production increased 12.8-fold following lipopolysaccharide stimulation, with COX-2 accounting for 89% of induced synthesis. These findings clarify the biochemical basis for selective COX inhibition and inform development of safer anti-inflammatory agents.