Abstract
The primary objective of this study was to investigate the phosphodiesterase inhibitory activity of flavonoids using in silico docking studies. In this perspective, flavonoids like Apigenin, Baicalin, Chrysin, Genistein, Scopoletin and Caffeine were selected. Caffeine, a known phosphodiesterase inhibitor was used as the standard. In silico docking studies were carried out using AutoDock 4.2, based on the Lamarckian genetic algorithm principle. In the docking studies, three important parameters like binding energy, inhibition constant and intermolecular energy were determined. The results showed that all the selected flavonoids showed binding energy ranging between −7.59 kcal/mol to −5.66 kcal/mol when compared with that of the standard (−4.77 kcal/mol). Inhibition constant (2.72 μM to 71.03 μM) and intermolecular energy (−8.49 kcal/mol to −6.26 kcal/mol) of the flavonoids were coincide with the binding energy. All the selected flavonoids contributed phosphodiesterase inhibitory activity because of its functional groups. These molecular docking analyses could lead to the further development of potent phosphodiesterase inhibitors for the treatment of inflammatory disorders.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Cavasotto CN, Abagyan RA (2004) Protein flexibility in ligand docking and virtual screening to protein kinases. J Mol Biol 12:209–225
Chang MW, Ayeni C, Breuer S (2010) Virtual screening for HIV protease inhibitors: A comparison of AutoDock 4 and vina. PLoS One 5:119–155
Collignon B, Schulz R, Smith JC (2011) Task-parallel message passing interface implementation of Autodock4 for docking of very large databases of compounds using high-performance super-computers. J Comput Chem 32:1202–1209
Cosconati S, Forli S, Perryman AL, Harris R, Goodsell DS, Olson A (2010) Virtual Screening with AutoDock: Theory and Practice. Exp Opin Drug Disc 5:597–607
Cushnie TP, Lamb AJ (2011) Recent advances in understanding the antibacterial properties of flavonoids. Int J Antimicrob Agents 38(2):99–107
Fertel R, Weiss B (1976) Properties and drug responsiveness of cyclic nucleotide phosphodiesterases of rat lung. Mol Pharmacol 12:678–687
Formica JV, Regelson W (1995) Review of the biology of quercetin and related bioflavonoids. Food & Chem Toxicol 33:1061–1080
Gonzalez R, Ballester I (2011) Effects of flavonoids and other polyphenols on inflammation. Crit Rev Food Sci & Nut 51(4):331–362
Groot H, Rauen U (1998) Tissue injury by reactive oxygen species and the protective effects of flavonoids. Fund & Clin Pharmacol 12:249–255
Jeon Y, Heo Y, Kim C, Hyun Y, Lee T, Ro S, Cho J (2005) Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development. Cell & Mol Life Sci 62(11):1198–1220
Khairallah M, Khairallah RJ, Young ME (2008) Sildenafil and cardiomyocyte-specific cGMP signaling prevent cardiomyopathic changes associated with dystrophin deficiency. Pro Nat Acad Sci 105(19):7028–7033
Khodade P, Prabhu R, Chandra N (2007) Parallel implementation of Autodock. J App Crystall 40:598–599
Koppen H (2009) Virtual screening – what does it give us? Curr Opin Drug Disc & Dev 12:397–407
Lipworth BJ (2005) Phosphodiesterase-4 inhibitors for asthma and chronic obstructive pulmonary disease. Lancet 365:167–175
Madeswaran A, Umamaheswari M, Asokkumar K, Sivashanmugam T, Subhadradevi V, Jagannath P (2011) Docking studies: in silico lipoxygenase inhibitory activity of some commercially available flavonoids. Bangladesh J Pharmacol 6:133–138
Middleton EJ (1998) Effect of plant flavonoids on immune and inflammatory cell function. Adv Exp Med Biol 439:175–182
Nishiumi S, Miyamoto S (2011) Dietary flavonoids as cancer-preventive and therapeutic biofactors. Front Biosci 3:1332–1362
Park H, Lee J, Lee S (2006) Critical assessment of the automated AutoDock as a new docking tool for virtual screening. Proteins 65:549–554
Schames JR, Henchman RH, Seigel JS, Sotriffer CA, Ni H, Mccammon A (2004) Discovery of a Novel Binding Trench in HIV Integrase. J Med Chem 47:1879–1881
Schoichet BK (2004) Virtual screening of chemical libraries. Nature 43:862–865
Seeliger D, Groot BL (2010) Ligand docking and binding site analysis with PyMOL and Autodock/Vina. J Comput Aided Mol Des 24:417–424
Strada SJ, Uzunov P, Weiss B (1974) Ontogenetic development of a phosphodiesterase activator and the multiple forms of cyclic AMP phosphodiesterase of rat brain. J Neurochem 23:1097–1103
Umamaheswari M, Madeswaran A, Asokkumar K, Sivashanmugam T, Subhadradevi V, Jagannath P (2011) Study of potential xanthine oxidase inhibitors: In silico and in vitro biological activity biological activity biological activity biological activity. Bang J Pharmacol 6:117–123
Umamaheswari M, Madeswaran A, Asokkumar K, Sivashanmugam T, Subhadradevi V, Jagannath P (2012) Docking studies: Search for possible phytoconstituents for the treatment of gout. Int J Biol & Pharm Res 3(1):6–11
Wang C (2010) Phosphodiesterase-5 inhibitors and benign prostatic hyperplasia. Curr Opin Urol 20(1):49–54
Zhang HT, ZhaoY HuangY, Dorairaj NR, Chandler LJ, Donnell JM (2004) 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. Neuropsychopharmacol 29(8):1432–1439
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Madeswaran, A., Umamaheswari, M., Asokkumar, K. et al. In silico docking studies of phosphodiesterase inhibitory activity of commercially available flavonoids. Orient Pharm Exp Med 12, 301–306 (2012). https://doi.org/10.1007/s13596-012-0071-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13596-012-0071-5