Computational study ofPiper betleL. phytocompounds byinsilico and ADMETanalysis for prediction of potential xanthine oxidase inhibitory activity

Abstract

AbstractBackgroundXanthine oxidase (XO) enzyme is directly associated with pathogenesis of gout and indirectly with cancer, diabetes and metabolic syndromes. Allopurinol is a xanthine oxidase inhibitor which is useful in the treatment of gout but it causes side effects in humans and birds. Therefore, this study sought to identify the alternative compound from the natural resources with fewer side effects than the conventional ones.ObjectivesThe present study was designed to findout the xanthine oxidase inhibitory activity ofPiper betlephytocompounds in comparison with Allopurinol.MethodsThe detection of phytocompounds present in theP. betleL. extract was identified through Gas Chromatography Mass Spectrometry (GC-MS) analysis. Theinsilicoanalysis and ADMET properties were evaluated for the GC-MS derivedP.betlephytocompounds. Among the 32 phyto compounds ofP.betle, 18 were showed favourable affinity with xanthine oxidase and their different conformational structures were docked in schrodinger module with xanthine oxidase enzyme structure. The interpretation of results was carried out through GLIDE XP Scoring, GLIDE Energy, MM-GBSA energy and hydrogen bond and Pi-Pi interactions. Further the absorption, distribution, metabolism, excretion and toxicity (ADMET) analysis were also carriedout using QIKPRO programme.ResultsThe results revealed that, the twelve phytocompounds ofP.betleshowed GLIDE XP docking score (−6.881 to - 4.766 Kcal/mol) higher than allopurinol (−4.535 Kcal/mol) and 11 phytocompounds showed higher GLIDE energy (−42.822 Kcal/mol to - 36.706 Kcal/mol) than allopurinol (−32.676 Kcal/mol). Chromonol and eugenol were the most potential compounds ofP.betlewhich showed both hydrogen bond and Pi-Pi interactions with the target xanthine oxidase as that of standard drug allopurinol. The selected phytocompounds satisfied the ADME descriptors and have no violation of Lipinski’s rule of five.ConclusionsTheinsilicoand ADMET profile study on the phytocompounds ofP.betlepredicted their promising potential xanthine oxidase inhibition activity and they could be developed as alternate molecules against synthetic agents byinvivoexperiments for the treatment of xanthine oxidase associated diseases like hyperuricimia and cardiovascular disorders.