In silico investigation of two benzoxanthone-flavonoids: ADMET analysis and xanthine oxidase binding

Natural products often contain bioactive compounds such as polyphenols, flavonoids, benzoxanthones, and other phytochemicals that exhibit strong biological activities. Flavonoids, a class of polyphenolic compounds, are secondary metabolites found in various plant-based foods with potential applications in medicinal chemistry. They offer several medicinal benefits, including anticancer and anti-inflammatory properties as well as antioxidant activity and their ability to inhibit the xanthine oxidase enzyme. Xanthine oxidase (XO) is essential for purine metabolism, the process by which the body breaks down purines. According to published research, hypoxanthine undergoes hydroxylation by XO to form xanthine. This process involves oxidative hydroxylation of the substrate at the molybdenum (Mo) center, generating reactive oxygen species (ROS). Therefore, inhibiting XO could be a viable approach to managing diseases associated with the accumulation of uric acid and the production of ROS.To understand the interactions between the two selected benzoxanthone-flavonoids (Artonin E and (+)-Artobiloxanthone) and the XO enzyme, molecular docking was performed. For this study, we used the complex quercetin-XO from the RSC PDB (3NVY). Artonin E and (+)-Artobiloxanthone showed excellent stability inside the active site of the XO enzyme, with estimated docking scores of -9.64 and -7.99 kcal/mol, respectively. In addition, significant interactions, similar to those formed by the co-crystallized ligand, were present in the studied compounds, including hydrogen bonds and hydrophobic interactions with residues of the active site. Additionally, we conducted drug-likeness and ADMET property analyses of the compounds to evaluate their potential as therapeutic agents.