Theoretical and experimental study of flavones as inhibitors of xanthine oxidase

Inhibitory activities of 19 polyhydroxylated and polymethoxylated flavones towards xanthine oxidase have been obtained by accurate measurements of the dissociation constants of enzyme-inhibitor complexes (K-EI). A topological description of the congeneric series has been adopted to derive quantitative structure-activity relationships (QSAR) with the use of multiple linear regression analysis. For interpretative purposes, molecular orbital calculations have also been performed. Inhibition appears to involve flavones as donors and the anion at the C-7 hydroxyl as the most active form in solution. Substituents in the 4H-1-benzopyran-4-one moiety can directly affect the availability of the C-7 anion in solution; substituents in the 2-phenyl moiety are probably involved in secondary local interactions with the enzyme.