Study of potential xanthine oxidase inhibitors: In silico and in vitro biological activity
DOI:
https://doi.org/10.3329/bjp.v6i2.9175Keywords:
Allopurinol, AutoDock 4.2, Docking, Enzyme kinetics, Xanthine oxidaseAbstract
In an attempt to develop potent anti gout agents, coumarin derivatives and polyphenolic compounds were selected for present study. The docking energy of 2-benzyl coumarin was found to be -7.50 kcal/mol which was less than that of the standard allopurinol (-4.47 kcal/mol). All the selected compounds were found to exhibit lower binding energy (-7.50 to -4.68 kcal/mol) than allopurinol. Docking results confirm that selected compounds showed greater inhibition of xanthine oxidase due to their active binding sites. In xanthine oxidase assay, IC50 value of 2-benzyl coumarin was found to be 26 ± 1.16 µg/mL, whereas that of allopurinol was 24 ± 0.28 µg/mL. All the compounds exhibited IC50 values ranging between 26 ± 1.16 to 58 ± 0.74 µg/mL. In enzyme kinetic studies, coumarin derivatives showed competitive and polyphenolic compounds showed non competitive type of enzyme inhibition. It can be concluded that coumarin derivatives could be a remedy for the treatment of gout and related inflammatory disorders.
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Azam F, Prasad MVV, Thangavel N. Molecular docking studies of 1-(substituted phenyl)-3-(naphtha [1,2d] thiazol -2-yl) urea/thiourea derivatives with human adenosine A2A receptor. Bioinformation. 2011; 6: 330-34.
Borges F, Feranandes E, Roleira F. Progress towards the discovery of xanthine oxidase inhibitors. Curr Med Chem. 2002; 9: 195-217.
Breda A, Basso LA, Santos DS, de Azevedo Jr WF. Virtual screening of drugs: Score functions, docking, and drug design. Curr Computer-Aided Drug Design 2008; 4: 265-72.
Cavasotto CN, Abagyan RA. Protein flexibility in ligand docking and virtual screening to protein kinases. J Mol Biol. 2004; 12: 209-25.
Chang MW, Ayeni C, Breuer S. Virtual screening for HIV protease inhibitors: A comparison of AutoDock 4 and vina. PLoS ONE. 2010; 5: 119-55.
Goodsell DS, Morris GM, Olson AJ. Automated docking of flexible ligands: Applications of Autodock. J Mol Recog. 1996; 9: 1-5.
Hediger AM. Molecular physiology of urate transport. Physiology 2005; 20: 125-33.
Khodade P, Prabhu R, Chandra N. Parallel implementation of Autodock. J App Crystal. 2007; 40: 598-99.
Kimura Y, Ito H, Ohnishi R, Hatano T. Inhibitory effects of polyphenols on human cytochrome P450 3A4 and 2C9 activity. Food Chem Toxicol. 2010; 48: 429-35.
Konc J, Konc JT, Penca M, Janezic M. Binding-sites prediction assisting protein-protein docking. Acta Chim Slov. 2011; 58: 396401.
Morris G, Goodsell D, Halliday R. Automated docking using Lamarckian genetic algorithm and an empirical binding free energy function. J Comp Chem. 1998; 19: 1639-62.
Niu Y, Zhu H, Liu J, Fan H, Sun L, Lu W, Liu X, Li L. 3,5,2',4'-Tetrahydroxychalcone, a new non-purine xanthine oxidase inhibitor. Chem Biol Inter. 2011; 189: 161-66.
Pacher P, Mabley GJ, Soriano GF, Liaudet L, Komjati K, Szabo C. Endothelial dysfunction in aging animals: The role of poly(ADP-ribose) polymerase activation. Br J Pharmacol. 2002; 135: 1347-50.
Pacher P, Nivorozhkin A, Szabo C. Therapeutic effect of xanthine oxidase inhibitors: Renaissance half a century after the discovery of allopurinol. Pharmacol Rev. 2006; 58: 87-114.
Park H, Lee J, Lee S. Critical assessment of the automated AutoDock as a new docking tool for virtual screening. Proteins 2006; 65: 549-54.
Symons CRM, Taiwo AF, Petersen LR. Electron addition to xanthine oxidase. An electron spins resonance study of the effects of ionizing radiation. J Chem Soc. 1989; 85: 4063-74.
Umamaheswari M, Asokkumar K, Sivashanmugam AT, Remyaraju A, Subhadradevi V, Ravi TK. In vitro xanthine oxidase inhibitory activity of the fractions of Erythrina stricta Roxb. J Ethnopharmacol. 2009; 124: 646-48.
Umamaheswari M, Chatterjee TK. Hypouricemic and xanthine oxidase inhibitory activities of the fractions of Coccinia grandis L.Voigt. OPEM. 2008; 7: 477-84.
Umamaheswari M, Madeswaran A, Asokkumar K, Sivashanmugam AT, Subhadradevi V, Jagannath V. Docking studies: Search for possible phytoconstituents for the treatment of gout. Int J Biol Pharm Res. 2012; 3: 6-11.
Umamaheswari M, Madeswaran A, Asokkumar K, Sivashanmugam T, Subhadradevi V, Jagannath P. Discovery of potential xanthine oxidase inhibitors using in silico docking studies. Der Pharma Chemica. 2011; 3: 240-47.
Unno T, Sugimoto A, Kakuda T. Xanthine oxidase inhibitors from the leaves of Lagerstroemia species (L.) Pers. J Ethnopharmacol. 2004; 93: 391-95.
Werns SW, Grum CM, Ventura A, Hahn RA, Ho PP, Towner RD, Fantone JC, Schork MA, Lucchesi BR. Xanthine oxidase inhibition does not limit canine infarct size. Circulation 1991; 83: 995-1005.
Zhang S, Kumar K, Jiang X. DOVIS: An implementation for high throughput virtual ening using Autodock. BMC Bioinformatics. 2008; 9: 126-28.
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