Physicochemical features and structural analysis of xanthine oxidase as a potential therapeutic target to prevent gout

Abstract

The high uric acid level in blood can cause gouty arthritis. In the uric acid cycle, purines are converted to uric acid and the process is controlled through series of enzymes, of which, xanthine oxidase (XO) is a key enzyme responsible for the oxidation of xanthine to uric acid. XO has been used as a potential therapeutic target to control uric acid deposition, ultimately preventing gout. Various inhibitors of XO are being used as drugs to prevent uric acid deposition by inhibiting the overactivity of the enzyme. In this study, a molecular docking approach was used to evaluate the pharmacological properties and drug suitability of thirteen reported inhibitors of XO. All the inhibitors analyzed here were found suitable as oral drug candidates to cure gout by inhibiting the expression of XO with varying efficiencies except phytic acid. Fisetin, which is present in considerable amounts in different fruits and vegetables including strawberries, apple, cucumber, and onion, was scrutinized as the most efficient inhibitor of XO and suitable oral drug candidate amongst all reported inhibitors studied here. In conclusion, our study provides additional insights into the interaction properties and bioavailability of known putative inhibitors of XO as potential drug candidates to relieve gout.