فهرست نشریات علمی دسترسی آزاد ایران

Selective cyclooxygenase-2 inhibitors have gained prominence in anti-inflammatory drug development due to their potential to reduce inflammation while minimizing the gastrointestinal toxicity associated with non-selective NSAIDs. This study focuses on the synthesis, molecular docking, characterization, and evaluation of new 3-ethyl-1H-indole derivatives containing imidazolidinone pharmacophores as selective COX-2 inhibitors aimed at improving GI safety. Molecular docking studies predicted strong binding affinities for the synthesized compounds, with scores ranging from -11.35 to -10.40 kcal/mol, significantly higher than the reference drug meloxicam (-6.89 kcal/mol). The compounds were structurally confirmed using FT-IR and ¹H-NMR spectroscopy. ADME predictions further validated the drug-likeness and favorable pharmacokinetic profiles of the synthesized compounds. Preliminary in vivo anti-inflammatory activity was assessed using an egg-white-induced paw edema model in rats, where the compounds significantly reduced inflammation compared to ibuprofen. Compound IIb demonstrated the highest efficacy, with a prolonged reduction in paw edema. These findings indicate that the newly synthesized indole derivatives have potential as selective COX-2 inhibitors with promising anti-inflammatory properties and improved GI safety. Future studies will focus on further toxicity and enzymatic inhibition assays to fully characterize their safety and therapeutic potential.