"Unveiling the anti-inflammatory potential of coumarin-based Schiff base derivatives through structural characterization and in vitro and in vivo biological evaluation".

Abstract

BACKGROUND: Chronic inflammation contributes to several diseases, creating a need for effective anti-inflammatory agents. OBJECTIVE: This study aimed to synthesize, characterize, and evaluate coumarin-based Schiff base derivatives for anti-inflammatory activity. METHODS: Ten coumarin Schiff base derivatives (SB-1 to SB-10) were synthesized by condensing 7-amino-4-methylcoumarin with substituted aromatic aldehydes. The compounds were characterized using FT-IR and 1H NMR spectroscopy. In vitro activity was evaluated using the egg albumin denaturation assay. The most active compounds were assessed for acute toxicity and in vivo activity using carrageenan-induced paw edema in Wistar rats. Molecular docking was performed against COX-2 protein structures, and drug-likeness and ADME properties were predicted using SwissADME. RESULTS: SB-5 and SB-6 exhibited the highest in vitro activity, producing 82.65% and 73.46% inhibition of protein denaturation, respectively, at 250 µg/mL. At 200 mg/kg, SB-5 and SB-6 produced 46.02% and 41.29% inhibition of paw edemarespectively, whereas diclofenac sodium produced 66.90% inhibition at the dose evaluated. Both compounds were well tolerated in the acute toxicity study. Molecular docking indicated favorable interactions with COX-2 targets. SwissADME analysis showed compliance with Lipinski and Veber criteria and favorable gastrointestinal absorption and pharmacokinetic properties. CONCLUSION: SB-5 and SB-6 demonstrated promising preliminary anti-inflammatory activity and warrant further target-specific, pharmacological, pharmacokinetic, and toxicity studies to validate their potential for drug development.

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