Molecular Docking, Synthesis, Characterization and Preliminary Evaluation of some New ۳-Ethyl-۱𝐻-Indole Derivatives as Potential COX-۲ Inhibitors

Selective cyclooxygenase-۲ 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 ۳-ethyl-۱H-indole derivatives containing imidazolidinone pharmacophores as selective COX-۲ inhibitors aimed at improving GI safety. Molecular docking studies predicted strong binding affinities for the synthesized compounds, with scores ranging from -۱۱.۳۵ to -۱۰.۴۰ kcal/mol, significantly higher than the reference drug meloxicam (-۶.۸۹ 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-۲ 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.

کلیدواژه ها:

Indole derivatives ، COX-۲ inhibitors ، Molecular docking ، anti-inflammatory activity ، Imidazolidinone