Ligands from Propolis as Antioxidants through Inhibition of Xanthine Oxidase (XOD): An In Silico Exploration.

Excessive reactive oxygen species (ROS) contribute to various chronic diseases, and xanthine oxidase (XOD) is a significant source of ROS in human metabolism. Propolis, known for its antioxidant properties, contains bioactive compounds that may inhibit XOD and reduce ROS production. This study aimed to investigate the inhibitory potential of propolis-derived phytochemicals on XOD through in silico methods. We conducted molecular docking to assess binding affinities and interaction profiles of 48 propolis compounds with XOD’s active site. Key XOD interacting residues including Glu802, Arg880, Thr1010, and Glu1261 played a role in stabilizing the binding of lead compounds through hydrogen bonds and hydrophobic contacts. Compounds luteolin, apigenin, and acacetin exhibited high docking scores of -11.650, -11.470, and − 11.284 kcal/mol, respectively, indicating strong binding affinity than the common standards, febuxostat (-7.922 kcal/mol) and allopurinol (-5.707 kcal/mol). MMGBSA calculations supported these findings, with catechin, myricetin, and hesperetin showing favorable binding free energies of -53.48, -48.69, and − 48.40 kcal/mol. QSAR modeling further confirmed the inhibitory potential, with low IC50 values for the most active compounds. ADME-T analysis indicated high gastrointestinal absorption and favorable drug-likeness for several compounds, suggesting promising pharmacokinetic and pharmacodynamic properties. In conclusion, propolis compounds, particularly luteolin, apigenin, and acacetin, show significant potential as natural XOD inhibitors. These findings support further experimental validation of these compounds as antioxidant therapies for managing ROS-related diseases.