Virtual screening analysis and in-vitro xanthine oxidase inhibitory activity of some commercially available flavonoids

ABSTRACT

Allopurinol, the xanthine oxidase inhibitor, is the only drug available for the treatment of gout. We examined the xanthine oxidase inhibitory activity of some commercially available flavonoids such asepigallocatechin, acacatechin, myricetin, naringenin, daidzein and glycitein by virtual screening and in-vitro studies. The interacting residues within the complex model and their contact types were identified. The virtual screening analysis were carried out using AutoDock 4.2 and in-vitro xanthine oxidase inhibitory activity was carried out using xanthine as the substrate. In addition, enzyme kinetics was performed using LineweaverBurkplot analysis. Allopurinol, a known xanthine oxidase inhibitor was used as the standard. The docking energy of glycitein was found to be -8.49 kcal/mol which was less than that of the standard [-4.47 kcal/mol]. All the selected flavonoids were found to exhibit lower binding energy [-8.08 to -6.03 kcal/mol] than allopurinol. The docking results confirm that flavonoids showed greater inhibition of xanthine oxidase due to their active binding sites and lesser binding energies compared to allopurinol. This may be attributed to the presence of benzopyran ring in the flavonoids. In the xanthine oxidase assay, IC[50] value of glycitein was found to be 12 +/- 0.86 micro g/mL, whereas that of allopurinol was 24 +/- 0.28 micro g/mL. All the remaining compounds exhibited IC[50] values ranging between 22 +/- 0.64 to 62 +/- 1.18 micro g/mL. In the enzyme kinetic studies, flavonoids showed competitive type of enzyme inhibition. It can be concluded that flavonoids could be a promising remedy for the treatment of gout and related inflammatory disorders. Further in-vivo studies are required to develop potential compounds with lesser side effects