Computational drug discovery of potential TAU protein kinase I inhibitors using in silico docking studies
DOI:
https://doi.org/10.3329/bjp.v8i2.13886Keywords:
Alzheimer's disease, Binding energy, Flavonoids, Inhibition constant, tau proteinAbstract
The objective of the current study is to evaluate the tau protein kinase I 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. Memantine, a known neuro-receptor antagonist is currently used in the treatment of Alzheimer's disease. The results showed that all the selected flavonoids showed binding energy ranging between -7.07 kcal/mol to -4.85 kcal/mol when compared with that of the standard (-5.89 kcal/mol). Inhibition constant (6.62 µM to 280.05 µM) and intermolecular energy (-9.45 kcal/mol to -6.64 kcal/mol) of the ligands also coincide with the binding energy. These molecular docking analyses could lead to the further development of potent tau protein kinase I inhibitors for the treatment of Alzheimers disease. Further investigations on the above compounds and in vivo studies are necessary to develop potential chemical entities for the prevention and treatment of Alzheimer's disease.
Downloads
229
211 Read
4
References
Alonso A, Zaidi T, Novak M, Grundke-Iqbal I, Iqbal K. Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments. Proc Nat Acad Sci. 2001; 98: 6923-28.
Aung HT, Furukawa T, Nikai T, Niwa M, Takaya Y. Contribution of cinnamic acid analogues in rosmarinic acid to inhibition of snake venom induced hemorrhage. Bioorg Med Chem. 2011; 19: 2392-96.
Beker BY, Bakir T, Sonmezoglu I, Imer F, Apak R. Antioxidant protective effect of flavonoids on linoleic acid peroxidation induced by copper (II)/ascorbic acid system. Chem Phys Lipids. 2011; 8: 732-39.
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.
Billingsley ML, Kincaid RL. Regulated phosphorylation and dephosphorylation of tau protein: effects on microtubule interaction, intracellular trafficking and neurodegeneration. J Biochem. 1997; 323: 577-91.
Budakoti A, Bhat AR, Azam A. Synthesis of new 2-(5-substituted-3-phenyl-2-pyrazolinyl)-1,3-thiazolino[5,4-b]quinoxaline derivatives and evaluation of their antiamoebic activity. European J Med Chem. 2009; 44: 1317-25.
Buee L, Bussiere T, Buee-Scherrer V, Delacourte A, Hof PR. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Rev. 2000; 33: 95-130.
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.
Chassany O, Bonaz B, Bruley DES, Varannes S, Bueno L. Acute exacerbation of pain in irritable bowel syndrome: Efficacy of phloroglucinol and trimethyl phloroglucinol. A randomized, double-blind, placebo-controlled study. Alimen Pharmacol Ther. 2007; 25: 1115-23.
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.
Ekins S, Nikolsky Y, Nikolskaya T. Techniques: Applications of systems biology to absorption, distribution, metabolism, excretion and toxicity. Trends Pharmacol Sci. 2005; 26: 202-09.
Formica JV, Regelson W. Review of the biology of quercetin and related bioflavonoids. Food Chem Toxicol. 1995; 33: 1061-80.
Galluzzo P, Marino M. Nutritional flavonoids impact on nuclear and extranuclear estrogen receptor activities. Genes Nutr. 2006; 1: 161-76.
Hall GF, Patuto BA. Is tau ready for admission to the prion club? Prion 2012; 6: 1-6.
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.
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. Docking studies of aldose reductase inhibitory activity of commercially available flavonoids. Int J Biomed Pharmaceut Sci. 2013; 7: 7-11.
Shin RW, Iwaki T, Kitamoto T, Tateishi J. Hydrated autoclave pretreatment enhances tau immunoreactivity in formalin-fixed normal and Alzheimer's disease brain tissues. Lab Invest. 1991; 64: 693702.
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.
Additional Files
Published
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
