Synthesis, anti-inflammatory effects, molecular docking and molecular dynamics studies of 4-hydroxy coumarin derivatives as inhibitors of COX-II enzyme

Abstract

The research aimed to investigate the anti-inflammatory effect of 4-hydroxy coumarin derivatives on inflammatory response in rats and to estimate the toxicity of enumerated compounds (3-11) following acute exposure. Toxicity report was collected by oral dosing administered individually to rats on a scale of 10-3000 mg/kg, while an indication of toxicity was observed for ten days following the last given dose. The response to inflammation was estimated using the model of xylene-induced edema and the model of carrageenan-inflammation of the paw.Compounds were administered orally to animals at a once-daily dose for seven sequential days. Molecular docking studies with COX-II enzyme were used to explain deeply the activity of synthesized compounds. Furthermore, the in-silico results were quite consistent with biological activity. Interestingly, compounds 5 and 10 showing the highest binding points (lower values). Therefore, the molecular dynamics simulation study of the most active compounds 5 and 10 was performed.