Computational drug design of potential α-amylase inhibitors using some commercially available flavonoids
Keywords:Acarbose, Diabetes, Binding energy, Inhibition constant, Intermolecular energy
The primary objective of this study was to investigate the α-amylase inhibitory activity of flavonoids using in silico docking studies. In this perspective, flavonoids like biochanin, chrysin, hesperitin, morin, tricin and vitexycarpin were selected. Acarbose, a known α-amylase inhibitor was used as the standard. In silico docking studies were carried out using AutoDock 4.2, based on the Lamarckian genetic algorithm principle. The results showed that all the selected flavonoids showed binding energy ranging between -7.20 kcal/mol to -6.21 kcal/mol when compared with that of the standard (-2.94 kcal/mol). Inhibition constant (5.31 µM to 27.89 µM) and intermolecular energy (-8.99 kcal/mol to -7.41 kcal/mol) of the flavonoids also coincide with the binding energy. The α-amylase inhibitory activity of the selected flavonoids was in order of tricin > hesperitin > vitexycarpin > chrysin > morin > biochanin. These molecular docking analyses could lead to the further development of potent α-amylase inhibitors for the treatment of diabetes.
Bikadi Z, Hazai E. Application of the PM6 semiempirical method to modeling proteins enhances docking accuracy of AutoDock. J Cheminform. 2009; 1: 15-17.
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.
Collignon B, Schulz R, Smith JC. Task-parallel message passing interface implementation of Autodock4 for docking of very large databases of compounds using high-performance supercomputers. J Comput Chem. 2011; 32: 1202-09.
Cosconati S, Forli S, Perryman AL, Harris R, Goodsell DS, Olson A. Virtual screening with AutoDock: Theory and practice. J Exp Opin Drug Disc. 2010; 5: 597-607.
Formica JV, Regelson W. Review of the biology of quercetin and related bioflavonoids. Food Chem Toxicol. 1995; 33: 1061-80.
Groot H, Rauen U. Tissue injury by reactive oxygen species and the protective effects of flavonoids. Fundam Clin Pharmacol. 1998; 12: 249-55.
Gupta R, Gigras P, Mohapatra H, Goswami VK, Chauhan B. Microbial α-amylases: A biotechnological perspective. Process Biochem. 2003; 38: 1599-616.
Khairallah M, Khairallah RJ, Young ME. Sildenafil and cardiomyocyte-specific cGMP signaling prevent cardiomyopathic changes associated with dystrophin deficiency. Proc Nat Acad Sci. 2008; 105: 7028-33.
Konc J, Konc JT, Penca M, Janezic M. Binding-sites prediction assisting protein-protein docking. Acta Chim Solv. 2011; 58: 396-401.
Koppen H. Virtual screening: What does it give us? Curr Opin Drug Disc Dev. 2009; 12: 397-407.
Lamba HS, Bhargava CS, Thakur M, Bhargava S. αglucosidase and aldose reductase inhibitory activity in vitro and anti diabetic activity in vivo of Tribulus terrestris L. (dunal). Int J Pharm Pharmac Sci. 2011; 3: 270-72.
Li Y, Li C, Xu Q, Kang W. Antioxidant, α-glucosidase inhibitory activities in vitro and alloxan-induced diabetic rats protective effect of Indigofera stachyodes Lindl. root. J Med Plants Res. 2011; 5: 3321-28.
Madeswaran A, Umamaheswari M, Asokkumar K, Sivashanmugam T, Subhadradevi V, Jagannath P. Computational drug discovery of potential TAU protein kinase I inhibitors using in silico docking studies. Bangladesh J Pharmacol. 2013; 8: 131-35.
Madeswaran A, Umamaheswari M, Asokkumar K, Sivashanmugam T, Subhadradevi V, Jagannath P. In Silico docking studies of lipoxygenase inhibitory activity of comercially available flavonoids. Orient Pharm Exp Med. 2012; 12: 157-61.
Madeswaran A, Umamaheswari M, Asokkumar K, Sivashanmugam T, Subhadradevi V, Jagannath P. Discovery of potential aldose reductase inhibitors using in silico docking studies. J Comput Method Mol Design 2011; 1: 65-72.
Prakhov ND, Chernorudskiy LA, Gainullin RM. VSDocker: A tool for parallel high-throughput virtual screening using AutoDock on Windows-based computer clusters. Bioinformatics 2010; 26: 1374-75.
Sandeep G, Nagasree KP, Hanisha M, Kumar MMK. AUDocker LE: A GUI for virtual screening with AUTODOCK Vina. BMC Res Notes 2011; 4: 445-47.
Sarikaya E, Higassa T, Adachi M, Mikami B. Comparison of degradation abilities of α- and β-amylases on raw starch granules. Proc Biochem. 2000; 35: 711-15.
Seeliger D, Groot BL. Ligand docking and binding site analysis with PyMOL and Autodock/Vina. J Comput Aided Mol Design 2010; 24: 417-24.
Vianna R, Brault A, Martineau LC, Couture R. In vivo anti-diabetic activity of the ethanolic crude extract of Sorbus decora C. K. Schneid. (Rosacea): A medicinal plant used by Canadian James Bay Cree Nations to treat symptoms related to diabetes. Evid Based Complement Altern Med. 2011; 1: 10-15.
Wolfenden R, Lu X, Young G. Spontaneous hydrolysis of glycosides. J. Am. Chem. Soc. 1998; 120: 6814-15.
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