MOLECULAR DOCKING STUDY OF NEUROPROTECTIVE PLANT-DERIVED BIOMOLECULES IN PARKINSON’S DISEASE


Saurabh Kumar Jha, Pravir Kumar

Abstract


Objective: The objective of this study was to explore the therapeutic role of biomolecules in targeting the altered expression of Parkin in PD pathogenesis.

Methods: We employed various in silico tools such as drug-likeness parameters, namely, Lipinski filter analysis, Muscle tool for phylogenetic analysis, Castp Server for active site prediction, molecular docking studies using AutoDock 4.2.1 and LIGPLOT1.4.5 were carried out.

Results: Our results show that neuroprotective activity of Quercetin to be most effective and can provide their possible clinical relevance in PD. Further, initial screenings of the molecules were done based on Lipinski’s rule of five. CastP server used to predict the ligand binding site suggests that this protein can be utilized as a potential drug target. Finally, we have found Quercetin to be most effective amongst four biomolecules in modulating Parkin based on minimum inhibition constant, Ki and highest negative free energy of binding with the maximum interacting surface area in a course of docking studies.

Conclusion: This research could provide a potential therapeutic window for the treatment of PD.


Keywords


Parkinson's disease, Ubiquitin E3 ligase, Parkin, Molecular docking, Biomolecules

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References


Soto C. Unfolding the role of protein misfolding in neurodegenerative diseases. Nat Rev Neurosci 2003;4:49-60.

Hardy J, Orr H. The genetics of neurodegenerative diseases. J Neurochem 2006;97:1690-9.

Manoharan S, Guillemin GJ, Abiramasundari RS, Essa MM, Akbar M, Akbar MD. The role of reactive oxygen species in the pathogenesis of Alzheimer's disease, Parkinson's disease, and Huntington's disease: a mini review. Oxid Med Cell Longevity 2016. DOI:10.1155/2016/8590578

Sonia Angeline M, Sarkar A, Anand K, Ambasta RK, Kumar P. Sesamol and naringenin reverse the effect of rotenone-induced PD rat model. Neuroscience 2013;254:379-94.

Dias V, Junn E, Mouradian MM. The role of oxidative stress in Parkinson's disease. J Parkinson’s Disease 2013;3:461–91.

Leroy E, Boyer R, Auburger G. The ubiquitin pathway in Parkinson’s disease. Nature 1998;395:451–2.

Arduino DM, Esteves AR, Oliveira CR, Cardoso SM. Mitochondrial metabolism modulation: a new therapeutic approach for Parkinson's disease. CNS Neurol Disord Drug Targets 2010;9:105–19.

Ciechanover A, Kwon YT. Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies. Exp Mol Med 2015;47:e147.

Barry H. Antioxidants in human health and disease. Annu Rev Nut 1996;16:33–50.

Santos IM, Tomé Ada R, Saldanha GB, Ferreira PM, Militão GC, Freitas RM. Oxidative stress in the hippocampus during experimental seizures can be ameliorated with the antioxidant ascorbic acid. Oxid Med Cell Longevity 2009;2:214-21.

Kannappan S, Anuradha CV. Naringenin enhances insulin-stimulated tyrosine phosphorylation and improves the cellular actions of insulin in a dietary model of metabolic syndrome. Eur J Nutr 2010;49:101-9.

Bavithra S, Selvakumar K, Kumari P, R Krishnamoorthy, G Venkataraman, P Arunakaran J. Polychlorinated biphenyl (PCBs)-induced oxidative stress plays a critical role on cerebellar dopaminergic receptor expression: the ameliorative role of quercetin. Neurotox Res 2012;21:149-59.

Chen RS, Wu PL, Chiou RY. Peanut roots as a source of resveratrol. J Agric Food Chem 2002;50:1665–7.

Soleas GJ, Diamandis EP, Goldberg DM. Wine as a biological fluid: history, production, and role in disease prevention. J Clin Laboratory Anal 1997;11:287–313.

Tsu-Kung L, Shang-Der C, Yao-Chung C. Resveratrol partially prevents rotenone-induced neurotoxicity in dopaminergic SH-SY5Y cells through induction of heme oxygenase-1 dependent autophagy. Int J Mol Sci 2014;15:1625-46.

Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol 1990;215:403-10.

Edgar RC. MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 2004;5:113.

Arnold K, Bordoli L, Kopp J, Schwede T. The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics 2006;22:195-201.

Lipinski CA. Lead-and drug-like compounds: the rule-of-five revolution. Drug Discovery Today 2004;1:337–41.

Dundas J, Ouyang Z, Tseng J, Binkowski A, Turpaz Y, Liang J. CASTp: computed atlas of surface topography of proteins with structural and topographical mapping of functionally annotated residues. Nucleic Acids Res 2006;34:116-8.

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.

Wang, Chaodong. Parkin dosage mutations in patients with early-onset sporadic and familial Parkinson's disease in Chinese: an independent pathogenic role. Brain Res 2010;1358:30-8.

Mizuno, Yoshikuni. Progress in familial Parkinson’s disease. Parkinson’s disease and related disorders. Springer Vienna 2006;70 Suppl:191-204.

Pranjaligupta, Nishant Rai, Pankaj Gautam. Anticancer drugs as potential inhibitors of acrab-tolc of multi drug resistant escherichia coli: an in silico molecular modeling and docking study. Asian J Pharm Clin Res 2015;8:351-8.

Sri dharani R, Ranjitha R, Sripathi R, Ali muhammad KS, Ravi S. Docking studies in target proteins involved in antibacterial action mechanisms: alkaloids isolated from scutellaria genus. Asian J Pharm Clin Res 2016;9:121-5.

Maida Engels, Se Balaji B, Divakar S, Geetha G. ligand based pharmacophore modeling, virtual screening and molecular docking studies to design novel pancreatic lipase inhibitors. Int J Pharm Pharm Sci 2017;9:48-64.

Rigoberto Villanueva Guerrero, Rodolfo Abarca Vargas, Vera L. Petricevich, Chemical compounds and biological activity of an extract from bougainvillea x buttiana (var. rose) holttum and standl. Int J Pharm Pharm Sci 2017;9:42-6.




About this article

Title

MOLECULAR DOCKING STUDY OF NEUROPROTECTIVE PLANT-DERIVED BIOMOLECULES IN PARKINSON’S DISEASE

Keywords

Parkinson's disease, Ubiquitin E3 ligase, Parkin, Molecular docking, Biomolecules

DOI

10.22159/ijpps.2017v9i9.20445

Date

13-07-2017

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 9, Issue 9, 2017 Page: 149-155

Online ISSN

0975-1491

Statistics

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Authors & Affiliations

Saurabh Kumar Jha
Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University (Formerly DCE), Delhi 110042
India

Pravir Kumar
Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University (Formerly DCE), Delhi 110042
India


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