چكيده فارسي :
New drugs for the inhibition of the enzyme xanthine oxidase are in development and they have to be screened before being considered for preclinical and clinical evaluation. In order to understand the mechanism of ligand binding and to identify potent xanthine oxidase inhibitors, a study involving molecular docking and virtual screening has been performed[1]. The objective of the current study is to evaluate the xanthine oxidase inhibitory activity of three compounds using in silico docking studies. In this perspective, quercetin , allopurinol and a 1.4- dihydropyridine derivative were selected[2]. Allopurinol, a known xanthine oxidase inhibitor was used as the standard. In Silico docking studies were carried out using AutoDock 4.2, based on the Lamarckian genetic algorithm principle[3]. The two important parameters like binding energy and inhibition constant were determined. The results showed that all three selected compounds showed binding energy ranging between -7.0 kcal/mol to -4.4kcal/mol. The binding energy energy of , quercetin , 1.4 dihydropyridine derivative and allopurinol were -7.03 kcal/mol ,-5.20 kcal/mol and -4.4 kcal/mol respectively and inhibition constant were 6.85 μM , 360μM and 1040 μM respectively. The images of ligplot software showed that quercetin has three additional H-bonds comparing to other compounds. Regarding the data obtained for binding energies with docked target, docking outputs supported that higher binding energy of quercetincan be interpreted by additional H-bonds with the active sites of the receptor. These molecular docking analyses could lead to the further development of potent xanthine oxidase inhibitors for the prevention and treatment of gout and related inflammatory conditions.
