COMPUTATIONAL ANALYSIS OF PHYTOCOMPOUNDS PRESENT IN LEUCAS ASPERA TO TARGET PARKINSON’S DISEASE-CAUSING ALPHA-SYNUCLEIN

ASHTON MENEZES

doi:10.22159/ijms.2022.v10i6.46618

Authors

ASHTON MENEZES Department of Biotechnology, N.M.A.M. Institute of Technology, Nitte, Karnataka, India.

DOI:

https://doi.org/10.22159/ijms.2022.v10i6.46618

Keywords:

Phytocompounds, Leucas aspera, Alpha-synuclein, Parkinson’s disease, Antagonists

Abstract

Objective: Parkinson’s disorder is the second most prevalent neurodegenerative disorder in the world that manifests in both the motor and non-motor systems. The pathogenesis of the disorder involves alpha-synuclein in a variety of ways, and therefore, this protein can be appraised as a therapeutic target. In the present study, the bioactive phytocompounds from Leucas aspera were examined to establish their inhibitory activity against alpha-synuclein protein.

Methods: In this study, ten phytocompounds were selected from L. aspera and their efficacy to counteract Parkinson’s disease (PD)-causing alpha-synuclein was evaluated. The study was done computationally using Indian medicinal plants, phytochemistry, and therapeutics and PubChem to source information and molecular structures of the phytocompounds. Several other tools were used for pharmacological assessment of these compounds under ADME properties and ProTox-II was used for toxicity prediction.

Results: Molecular docking using PyRx and BIOVIA revealed that Baicalein and Leucasperones A were the best antagonists for 3Q25 Parkinson’s causing alpha-synuclein. Hence, these compounds can be used as potential candidates to produce drugs which help prevent PD.

Conclusion: Since ancient times, plants have been used to cure several maladies. The phytochemical Baicalein and Leucasperones A present in L. aspera, bind to disease causing alpha-synuclein, and help in disease management.

References

Beitz JM. Parkinson’s disease: A review. Front Biosci (Schol Ed) 2014;6:65-74.

Davie CA. A review of Parkinson’s disease. Br Med Bull 2008;86:109-27.

Sveinbjornsdottir S. The clinical symptoms of Parkinson’s disease. J Neurochem 2016;139 Suppl 1:318-24.

Lücking CB, Brice A. Alpha-synuclein and Parkinson’s disease. Cell Mol Life Sci 2000;57:1894-908.

Stefanis L. α-Synuclein in Parkinson’s disease. Cold Spring Harb Perspect Med 2012;2:a009399.

Prajapati MS, Patel JB, Modi K, Shah MB. Leucas aspera: A review. Pharmacogn Rev 2010;4:85-7.

Chew AL, Jessica JJ, Sasidharan S. Antioxidant and antibacterial activity of different parts of Leucas aspera. Asian Pac J Trop Biomed 2012;2:176-80.

Mangathayaru K, Lakshmikant J, Sundar NS, Swapna R, Grace XF, Vasantha J. Antimicrobial activity of Leucas aspera flowers. Fitoterapia 2005;76:752-4.

Babu A, Mohamed MS, Jaikumar K, Anand D, Saravanan P. In-vitro antifungal activity of leaf extracts of Leucas aspera and Leucas zeylanica. Int J Pharm Sci Res 2016;7:752-6.

Rahman MS, Sadhu SK, Hasan CM. Preliminary antinociceptive, antioxidant and cytotoxic activities of Leucas aspera root. Fitoterapia 2007;78:552-5.

Mohan A, Nair SV, Lakshmanan VK. Leucas aspera nanomedicine shows superior toxicity and cell migration retarded in prostate cancer cells. Appl Biochem Biotechnol 2017;181:1388-400.

Islam AK, Ohno O, Suenaga K, Kato-Noguchi H. Two novel phytotoxic substances from Leucas aspera. J Plant Physiol 2014;171:877-83.

Mohanraj K, Karthikeyan BS, Vivek-Ananth RP, Chand RP, Aparna SR, Mangalapandi P, et al. IMPPAT: A curated database of Indian medicinal plants, phytochemistry and therapeutics. Sci Rep 2018;8:4329.

Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, et al. PubChem in 2021: New data content and improved web interfaces. Nucleic Acids Res 2021;49:D1388-95.

De Beer TA, Berka K, Thornton JM, Laskowski RA. PDBsum additions. Nucleic Acids Res 2014;42:D292-6.

Laskowski RA, MacArthur MW, Moss DS, Thornton JM. PROCHECK: A program to check the stereochemical quality of protein structures. J Appl Crystallogr 1993;26:283-91.

Kim M, Kim H, Lee W, Lee Y, Kwon SW, Lee J. Quantitative shotgun proteomics analysis of rice anther proteins after exposure to high temperature. Int J Genomics 2015;2015:238704.

McWilliam H, Li W, Uludag M, Squizzato S, Park YM, Buso N, et al. Analysis tool web services from the EMBL-EBI. Nucleic Acids Res 2013;41:W597-600.

BIOVIA DS. BIOVIA Discovery Studio Visualizer. Vol. 20. California, United States: BIOVIA Software Version; 2017. p. 779.

Xiong G, Wu Z, Yi J, Fu L, Yang Z, Hsieh C, et al. ADMETlab 2.0: An integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Res 2021;49:W5-14.

Banerjee P, Eckert AO, Schrey AK, Preissner R. ProTox-II: A webserver for the prediction of toxicity of chemicals. Nucleic Acids Res 2018;46:W257-63.

Yang ZY, Yang ZJ, Dong J, Wang LL, Zhang LX, Ding JJ, et al. Structural analysis and identification of colloidal aggregators in drug discovery. J Chem Inf Model 2019;59:3714-26.

Dallakyan S, Olson AJ. Small-molecule library screening by docking with PyRx. Methods Mol Biol 2015;1263:243-50.

Goetz CG. The history of Parkinson’s disease: Early clinical descriptions and neurological therapies. Cold Spring Harb Perspect Med 2011;1:a008862.