Mechanistic approach towards interaction of newly synthesized Hesperidin derivatives against xanthine oxidase

Xanthine oxidase is an important enzyme of purine catabolism pathway and has been associated directly in pathogenesis of gout and indirectly in many pathological conditions like cancer, diabetes and metabolic syndrome. In this research Hesperidin, a bioactive flavonoid was explored to determine the capability of itself and its derivatives to inhibit xanthine oxidase. The design and synthesis of Hesperidin derivatives hybridized with hydrazines to form hydrazides and anilines was performed with the help of molecular docking. The synthesized compounds were evaluated for their antioxidant and xanthine oxidase inhibitory potential. The enzyme kinetic studies performed on newly synthesized derivatives showed a potential inhibitory effect on XO ability in competitive manner with IC₅₀ value ranging from 00.263 μM - 14.870 μM and 3HDa₁ was revealed as most active derivative. Molecular simulation revealed that new Hesperidin derivatives interacted with the amino acid residues PHE798, GLN1194, ARG912, THR585, SER1080 and MET1038 positioned inside the binding site of XO. Results of antioxidant activity revealed that all the derivatives showed very good antioxidant potential. Taking advantage of molecular docking, this hybridization of two natural constituent could lead to desirable xanthine oxidase inhibitors with improved activity.