Molecular docking and in silico ADMET studies of silibinin and glycyrrhetic acid anti-inflammatory activity

Purpose: To use in silico docking analysis and ADMET prediction of silibinin and glycyrrhetic acid to determine their pharmacokinetic and pharmacodynamic properties as therapeutic molecules against inflammatory disorders.Methods: The study utilized plant-derived compounds with known anti-inflammatory activity. Three important enzymes, including COX-2, 5β-reductase and phospholipase A2, that are involved in the mediation of inflammatory processes, were chosen as protein targets for the ligands (silibinin and glycyrrhetic acid). Q-Site Finder and admetSAR were employed for active site prediction and ADMET profile, respectively. Furthermore, protein-ligand complexes were visually inspected by LigPlot and Chimera.Results: Post-docking analysis confirmed strong interaction of silibinin and glycyrrhetic acid with their respective targets. ADMET profiles for both compounds were very promising. Both ligands (silibinin and glycyrrhetic acid) showed strong binding energy for all three target proteins (-7.5 to -10.9 kcal/mol). Moreover, Asp347, Gln350, Gly354, Gln192, His351, Ser579 and Phe580 were the common interacting residues in the target proteins for both ligands.Conclusion: Glycyrrhetic acid possesses superior ADMET profile to silibinin. Hydrophobic interactions between the two ligands (glycyrrhetinic acid and silibinin) and the three target proteins (COX-2, phospholipase A2 and 5β-reductase) are significant.Keywords: Silibinin, Glycyrrhetic acid, ADMET, Docking studies, Phospholipase A2, COX-2, 5β-Reductas