Docking studies: In silico phosphodiesterase inhibitory activity of commercially available flavonoids
DOI:
https://doi.org/10.3329/bjp.v7i1.10595Keywords:
Algorithm, Binding energy, Inhibition constant, Intermolecular energyAbstract
The objective of the current study is to evaluate the phosphodiesterase inhibitory activity of flavonoids using in silico docking studies. 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 -7.50 kcal/mol to -6.61 kcal/mol when compared with that of the standard (-4.77 kcal/mol). Inhibition constant (3.17 µM to 14.36 µM) and intermolecular energy (-9.29 kcal/mol to -8.70 kcal/mol) of the ligands also coincide with the binding energy. All the selected flavonoids contributed better phosphodiesterase inhibitory activity because of its structural parameters. Benzopyran ring in the flavonoids are majorly contributed its activity. These molecular docking analyses could lead to the further development of potent phosphodiesterase inhibitors for the treatment of inflammatory diseases.
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Bikadi Z, Hazai E. Application of the PM6 semi-empirical 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 super-computers. 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.
Jeon Y, Heo Y, Kim C, Hyun Y, Lee T, Ro S, Cho J. Phosphodiesterase: Overview of protein structures, potential therapeutic applications and recent progress in drug development. Cell Mol Life Sci. 2005; 62: 1198220.
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.
Madeswaran A, Umamaheswari M, Asokkumar K, Sivashanmugam T, Subhadradevi V, Jagannath P. In silico docking studies of lipoxygenase inhibitory activity of commercially 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.
Middleton EJ. Effect of plant flavonoids on immune and inflammatory cell function. Adv Exp Med Biol. 1998; 439: 175-82.
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.
Rotella DP. Phosphodiesterase 5 inhibitors: Current status and potential applications. Nature Rev Drug Disc. 2012; 1: 674-82.
Saito T, Sugimoto N, Ohta K, Shimizu T, Ohtani K, Nakayama Y, Nakamura T, Hitomi Y, Nakamura H, Koizumi S, Yachie A. Phosphodiesterase inhibitors suppress Lactobacillus casei cell-wall-induced NF-?B and MAPK activations and cell proliferation through Protein Kinase Aor exchange protein activated by cAMP-dependent signal pathway. Scienti?c World J. 2012.
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.
Seeliger D, Groot BL. Ligand docking and binding site analysis with PyMOL and Autodock/Vina. J Comput Aided Mol Des. 2010; 24: 417-24.
Umamaheswari M, Madeswaran A, Asokkumar K, Sivashanmugam T, Subhadradevi V, Jagannath P. Study of potential xanthine oxidase inhibitors: In silico and in vitro biological activity biological activity biological activity biological activity. Bangladesh J Pharmacol. 2011; 6: 117-23.
Wang C. Phosphodiesterase-5 inhibitors and benign prostatic hyperplasia. Curr Opin Urol. 2010; 20: 4954.
Zhang HT, Zhao Y, Huang Y, Dorairaj NR, Chandler LJ, Donnell JM. Inhibition of the phosphodiesterase 4 (PDE4) enzyme reverses memory deficits produced by infusion of the MEK inhibitor U0126 into the CA1 subregion of the rat hippocampus. Neuropsychopharmacology 2004; 29: 1432-39.
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