Title:In-silico Design and ADMET Studies of Natural Compounds as Inhibitors of Xanthine Oxidase (XO) Enzyme
VOLUME: 18 ISSUE: 6
Author(s):Neelam Malik, Priyanka Dhiman and Anurag Khatkar*
Affiliation:Incharge,Laboratory for Preservation Technology and Enzyme Inhibition Studies, Department of Pharmaceutical Sciences,M.D.University, Rohtak, Haryana, Incharge,Laboratory for Preservation Technology and Enzyme Inhibition Studies, Department of Pharmaceutical Sciences,M.D.University, Rohtak, Haryana, Incharge, Laboratory for Preservation Technology and Enzyme Inhibition Studies, Department of Pharmaceutical Sciences, M.D.University, Rohtak, Haryana
Keywords:Natural products, xanthine oxidase, virtual screening, MM-GB/SA, ADMET.
Abstract:Background: Xanthine oxidase a ubiquitous enzyme has been found to be involved in various pathological
disorders including gout, hyperuricemia, inflammation, oxidative stress and cardiovascular diseases. Inhibitors of
xanthine oxidase thus find a crucial role in the therapeutic treatment of these deadly diseases.
Objective: Considering the side effects of today’s treatment regimen here we choose nature based compounds to act
as xanthine oxidase inhibitors. In the present work, we performed in-silico docking of natural compounds to reveal
the underlying mechanism of inhibition of xanthine oxidase. Further filtration of screened compounds with ADMET
studies has been performed.
Method: An in-house library of natural compounds screened through ADMET profile for the drug likeliness property
was approached for docking studies using Schrödinger suite. Calculation of docking score was done by glide
module and free binding energy calculations were performed through MM/GBSA software.
Results: Natural leads having better pharmacokinetic profile and mechanism of inhibition were obtained. Docking
score, binding energy and different forces involved in interaction were calculated for the top-ranked molecules and
good comparison with the standard drugs was achieved
Conclusion: Compounds having potential therapeutic activity with low systematic toxicity has been identified
against xanthine oxidase which could serve as pharmacophore for the design and synthesis of new drug-like molecules
