Akademik Veri Yönetim Sistemi
Chemistry and Biodiversity, cilt.23, sa.5, 2026 (SCI-Expanded, Scopus)
This research presents the design, synthesis, and thorough evaluation of a new series of benzofuran-1,4-dihydropyridine hybrids (4a–i) as potential multi-target anti-inflammatory drugs. These compounds were created through an optimized multistep process and examined using a combination of in silico, in vitro, and in vivo methods. Molecular docking revealed a potential dual-target profile, with the leading compounds showing strong predicted binding to both COX-2 and TNF-α. Notably, compound 4i demonstrated the highest affinity for COX-2 (MolDock score = −181.002 kcal/mol), with good selectivity over COX-1 (Δ = −21.35), and also showed one of the strongest affinities for TNF-α (−174.847 kcal/mol). Molecular dynamics simulations confirmed the stability of the 4i-COX-2 complex. This in silico effectiveness was supported by strong in vitro anti-inflammatory activity (eg. 10.09 µg/mL for IC50 of 4b in hypotonicity-induced hemolysis). Notably, the compounds showed excellent in vivo activity in a carrageenan-induced paw edema model, with 4i achieving 91.5% inhibition at 90 min. Histological analysis confirmed that the lead compounds were highly gastrointestinal (GI)-sparing, consistent with their predicted COX-2 selectivity. No liver damage was observed, and platelet count remained normal (4i). Overall, this study identifies compound 4i as a potent, orally active, and safe antinflammatory candidate with potential dual mechanisms.