Bridging the gap with amide linkers: rational design, synthesis, and multi-target evaluation of sulfonamide/acetamide-NSAID hybrids as dual COX-2/5-LOX inhibitors

Abstract

AIM: Novel hybrids of ibuprofen and naproxen were designed as dual COX-2/5-LOX inhibitors to create safer anti-inflammatory drugs. MATERIALS AND METHODS: The prodrugs were developed through a hybridization molecular approach; their potency against COX-1, COX-2, and 5-LOX was assessed, alongside measurements of PGE2 levels, NO scavenging, and mTOR and Nrf2 protein expression. Molecular docking was used to predict binding interactions. RESULTS: values of 3.1 and 4.2 µM. CONCLUSION: The new hybrids exhibit strong COX-2/5-LOX inhibition, suggesting their structural framework is crucial for developing safer anti-inflammatory drugs.