title: In-silico Design and ADMET Studies of Natural Compounds as Inhibitors of Xanthine Oxidase (XO) Enzyme.
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.
  
  
  METHODS
  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.
authors.affiliation: Incharge,Laboratory for Preservation Technology and Enzyme Inhibition Studies, Department of Pharmaceutical Sciences,M.D.University, Rohtak, Haryana, India.
authors.forename: Neelam
authors.initials: N
authors.lastname: Malik
authors.affiliation: Incharge,Laboratory for Preservation Technology and Enzyme Inhibition Studies, Department of Pharmaceutical Sciences,M.D.University, Rohtak, Haryana, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Dhiman
authors.affiliation: Incharge, Laboratory for Preservation Technology and Enzyme Inhibition Studies, Department of Pharmaceutical Sciences, M.D.University, Rohtak, Haryana, India.
authors.forename: Anurag
authors.initials: A
authors.lastname: Khatkar
mesh_terms: D000818:Animals; D001665:Binding Sites; D001688:Biological Products / Q000494:pharmacology*; D018938:Caco-2 Cells; D003198:Computer Simulation; D004285:Dogs; D015195:Drug Design; D006801:Humans; D008024:Ligands; D061985:Madin Darby Canine Kidney Cells; D062105:Molecular Docking Simulation; D012709:Serum Albumin / Q000378:metabolism; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D001688:Biological Products; D008024:Ligands; D012709:Serum Albumin; D014969:Xanthine Oxidase
keywords: ADMET; MM-GB/SA; Natural products; virtual screening; xanthine oxidase