Synthesis, characterization and xanthine oxidase inhibition of Cu(II)–chrysin complex

Abstract

Xanthine oxidase (XO) is a key enzyme catalyzing hypoxanthine to xanthine and then uric acid causing hyperuricemia. A Cu(II) complex of chrysin was synthesized and characterized by UV–vis absorption, Fourier transform infrared, nuclear magnetic resonance (1H NMR) and mass spectroscopy studies. The interaction of Cu(II)-complex with XO was investigated by spectroscopic methods and molecular simulation. The Cu(II)-chrysin complex exhibited a better inhibitory ability (IC50=0.82±0.034μM) against XO than its corresponding ligands chrysin and Cu2+ in a mix-competitive manner. The binding affinity of Cu(II)-chrysin complex with XO was much higher than that of chrysin. The hydrogen bonds and van der Waals forces played main roles in the binding. Analysis of circular dichroism spectra indicated that the complex induced the conformational change of XO. The molecular simulation found that the Cu(II)-chrysin complex inserted into the active cavity of XO with Cu acting as a bridge, occupying the catalytic center of the enzyme to avoid entry of the substrate xanthine, leading to the inhibition of XO. This study may provide new insights into the inhibition mechanism of the Cu(II)-chrysin complex as a promising XO inhibitor and its potential application for the treatment of hyperuricemia.