IN SILICO DOCKING APPROACH FOR ANTIATHEROSCLEROTIC ACTIVITY OF PHYTOCONSTITUENTS OF CORCHORUS AESTUANS AND ADMET PREDICTION
Abstract
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Objective: Atherosclerosis is a persistent inflammatory condition within the arterial wall characterized by alterations in lipid metabolism. Liver
X alpha receptor is highly expressed in liver could regulate the cholesterol metabolism and suppress the inflammatory genes, so that its activation
prevents atherosclerosis. The Corchorus aestuans possess anti-atherosclerotic property along with its anti-hyperglycemic activity. The objective of the
present study is to investigate the anti-atherosclerotic activity of the C. aestuans leaves against Liver X alpha receptor by using GOLD study.
Methods: 3-Dimensional structure of Liver X alpha receptor (Protein Date Bank ID - 3IPQ) was retrieved using Protein Data Bank. Phytochemical
molecules were retrieved from the pubchem database and the 2D chemical structures were generated from SMILES notation (Simplified Molecular
Input Line Entry Specification) by using the Chemsketch Software. Screenings of different docked complex were performed by GOLD study. Absorption,
distribution, metabolism, excretion and toxicity properties for all molecules is predicted by using ADMET structure-activity relationship database.
Results: Among the 14 phytochemicals, E-7-Tetradecenol was found to be the top compound with highest Gold score of 26.99.
Conclusion: Our study suggests that phytochemicals from C. aestuans leaves may act as better leads and in turn prevent atherosclerosis.
Keywords: Atherosclerosis, Corchorus aestuans, Liver X alpha receptor, GOLD, Absorption, Distribution, Metabolism, Excretion and Toxicity.
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Li AC, Glass CK. PPAR- and LXR-dependent pathways controlling lipid metabolism and the development of atherosclerosis. J Lipid Res 2004;45(12):2161-73.
Lund EG, Menke JG, Sparrow CP. Liver X receptor agonists as potential therapeutic agents for dyslipidemia and atherosclerosis. Arterioscler Thromb Vasc Biol 2003;23(7):1169-77.
Rader DJ, Daugherty A. Translating molecular discoveries into new therapies for atherosclerosis. Nature 2008;451(7181):904-13.
Miller A, Crumbley C, Prüfer K. The N-terminal nuclear localization sequences of liver X receptors alpha and beta bind to importin alpha and are essential for both nuclear import and transactivating functions. Int J Biochem Cell Biol 2009;41(4):834-43.
Houghton PJ. The role of plants in traditional medicine and current therapy. J Altern Complement Med 1995;1(2):131-43.
Scott T. Exploring the universe of ayurvedic botanicals to manage bacterial infections. Clin Nutr Insights 1998;6(17):1-3.
Gamble JS. Flora of the presidency of Madras. Vol. 1. Dehradun, India: Bishen Singh Mahendra Pal Singh, Published under the Secretary of State for India in Council 4; s1997.
Heinrich M. Plant resources of South-East Asia, no. 12 (1). Medicinal and poisonous plants 1. Phytochemistry 2000;53:619-20.
Chopra RN, Chopra IC, Handa KL, Kapoor CD. Indigenous Drugs of India. Kolkatta: UN Dhar and Sons; 1958. p. 501-2.
Satyavati GV, Raina MK, Sharma M. Medicinal Plants of India. Vol. I. New Delhi: ICMR; 1976. p. 278-81.
Khan MS, Bano S, Javed K, Mueed MA. J Sci Indian Res 2006;65:283‑98.
Dhanalakshmi R, Manavalan R. Determination of bioactive constituents of leaves of Corchorus aestuans (L.) by GC – MS Analysis. Int J Pharm Pharm Sci 2014;6(9):248-51.
Garrett MM, Lim-Wilby M. Molecular docking. Methods Molecular Biologyâ„¢. Vol. 443. 2008. p. 365-82.
Brito MA. Pharmacokinetic study with computational tools in the medicinal chemistry course. Braz J Pharm Sci 2011;47:797.
Jones G, Willett P, Glen RC, Leach AR, Taylor R. Development and validation of a genetic algorithm for flexible docking. J Mol Biol 1997;267(3):727-48.
Cheng F, Li W, Zhou Y, Shen J, Wu Z, Liu G, et al. admetSAR: A comprehensive source and free tool for assessment of chemical ADMET properties. J Chem Inf Model 2012;52:3099-105.
O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR. Open Babel: An open chemical toolbox. J Cheminform 2011;3:33.
Balakin KV, Ivanenkov YA, Savchuk NP, Ivashchenko AA, Ekins S. Comprehensive computational assessment of ADME properties using mapping techniques. Curr Drug Discov Technol 2005;2(2):99-113.
Nissink JW, Murray C, Hartshorn M, Verdonk ML, Cole JC, Taylor R. A new test set for validating predictions of protein-ligand interaction. Proteins 2002;49:457-71.
Stamatovic SM, Keep RF, Andjelkovic AV. Brain endothelial cell-cell junctions: How to open†the blood brain barrier. Curr Neuropharmacol 2008;6(3):179-92.
Guengerich FP. Cytochromes P450, drugs, and diseases. Mol Interv 2003;3(4):194-204.
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