INSILICO EVALUATION OF ANTISMOKING ACTIVITY OF ERYTHRININE: A COMPUTATIONAL COMPARISON AGAINST CYTISINE
Abstract
Objectives: Erythrinine is a new ring-C-oxygenated Erythrina alkaloid from plant sources Erythrina Indica. The aim of this study is to investigate the smoking cessation activity of Erythrinine and its analogues using in silico computational approach.
Methods: Quantitative structure-affinity relationship approach has been employed to determine the antismoking activity of Erythrinine and its analogues. Multiple molecular docking analyses was carried out using Auto dock 4.2 to determine the inhibitory constants of designed compounds. Multiple linear regression analyses using SPSS 17.0 were carried out to build quantitative structure-affinity relationship model. Computation of descriptors was done using Molecular Operating Environment. All molecular visualizations were done using Pymol.
Results: The inhibitory constants of Erythrinine and Cytisine were found to be 5.95 and 30.23µM with negative binding energies of 7.13 and 6.17kcal/Mol respectively. A quantitative structure-affinity relationship model was built with a correlation coefficient of 0.96. Compound 12, 11, 8 and 7 were found to be highly active with inhibitory constants in the range of nanomolar concentrations.
Conclusion: A quantitative structure-affinity relationship model with a strong correlation coefficient of 0.96 endorses that Erythrinine is having a strong affinity with α4β2 nACh receptors as Cytisine. Hence, the comparative study concluded that Erythrinine may use as an antismoking agent.
Keywords: Erythrinine, Cytisine, Docking studies and smoking session.
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References
Centers for disease control and prevention. Quick Stats: Number of Deaths from 10 Leading Causes—National Vital Statistics System, United States, 2010. Morbidity and Mortality Weekly Report; 2013. p. 62; 155.
John RH. Motivating and helping smokers to stop smoking. J Gen Intern Med 2003;18:1053–7.
Fiore MC, Bailey WC, Cohen SJ. Treating tobacco use and dependence: clinical practice guideline. Rockville, MD: US Dept of Health and Human Services, Public Health Service; 2000. p. 7-9.
Glassman AH, Helzer JE, Covey LS. Smoking, smoking cessation, and major depression. JAMA 1990;264:1546-9.
Hall SM, Munoz R, Reus V. Smoking cessation, depression and dysphoria. NIDA Res Monogr 1991;105:312-3.
Glass RM. Blue mood, blackened lungs: depression and smoking. JAMA 1990;264:1583-4.
Hughes JR. Dependence potential and abuse liability of nicotine replacement therapies. In: Pomerleau O, Pomerleau C, eds. Progress in clinical evaluation. New York: Alan R. Liss; 1988. p. 261-77.
Covey LS, Glassman AH, Stetner F. Depression and depressive symptoms in smoking cessation. Compr Psychiatry 1990;31:350-4.
Hall SM, Munoz RF, Reus VI. Cognitive-behavioral intervention increases abstinence rates for depressive-history smokers. J Consulting Clin Psychol 1994;62:141-6.
Shiffman S. Relapse following smoking cessation: a situational analysis. J Consult Clin Psychol 1982;50:71-86.
Bencherif M, Schmitt JD, Bhatti BS, Crooks P, Caldwell WS, Lovette ME, et al. The heterocyclic substituted pyridine derivative (±)-2-(3-pyridinyl)-1-azabicyclo [2.2.2] octane (RJR-2429): a selective ligand at nicotinic acetylcholine receptors. J Pharmacol Exp Ther 1988;284:886-94.
YE Slater. Halogenated cytisine derivatives as agonists at human neuronal nicotinic acetylcholine receptor subtypes. Neuropharmacology 2003;44:503-15.
Kazuo Ito, Hiroshi Furukawa, Hitoshi Tanaka. The structure of erythrinine, a new alkaloid from Erythrina indica Lam. J Chem Soc D 1970:1076-77. Doi:10.1039/C29700001076. [Article in Press]
Muegge I, Rarey M. In: Reviews in computational chemistry. VCH Publishers: New York; 2001. p. 1-2.
Frank W Bell, Amanda S Cantrell, Marita Hoegberg, S Richard Jaskunas, Nils Gunnar Johansson, Christopher L Jordan, et al. Phenethylthiazolethiourea (PETT) compounds, a new class of HIV-1 reverse transcriptase inhibitors. 1. Synthesis and basic structure-activity relationship studies of PETT analogs. J Med Chem 1995;38:4929-36.
Vieth M. Cummins. DoMCoSAR: a novel approach for establishing the docking mode that is consistent with the structure-activity relationship. Application to HIV-1 protease inhibitors and VEGF receptor tyrosine kinase inhibitors. J Med Chem 2000;43:3020.
Natalie Walker, Colin Howe, Marewa Glover, Hayden McRobbie, Joanne Barnes, Vili Nosa, et al. Cytisine versus nicotine for smoking cessation. N Engl J Med 2014;371:25.