Molecular Docking Study on the Anti-inflammatory Effect of Osthol and Its Derivatives Towards Human p38alpha MAP kinase V

Abstract

Human p38alpha Mitogen Activated Protein kinase (MAPp38), an isoform of MAP protein family is well known to participate in the inflammatory processes. Recent pharmacological studies on osthol, a natural coumarin derivative, report its anti-inflammatory effect. We aim to analyze few of the semi synthetic derivatives of osthol for the possibility of exhibiting the anti-inflammatory effect into MAPp38. In addition to the known semi synthetic derivatives, osthol ethane thiol complex (OET), osthol cyclized derivative, osthol bromo methoxy derivative (OBM), osthenol and osthol ritter product (ORP), we synthesized four more osthol derivatives, osthol bromo hydroxy derivative (OBH), epoxy osthol, osthol bromo acetoxy derivative (OBA) and osthol tandem bromo isomerized product (OTBi) to analyse the anti-inflammatory effect into MAPp38. Prior to docking simulations using Autodock, we also calculated the drug likeness score, bioactivity and ADME properties of osthol and its derivatives through the in silico techniques. All the ligands were found to exhibit good druggable character as per Lipinski rule of 5. Docking results show interaction between the selected ligands into MAPp38, except for osthol cyclized derivative showing no interaction. The best docking simulations was reported by OBH, interacting through three hydrogen bonds with the lowest binding energy, -6.98 kcal/mol