International Journal of Bioinformatics and Biomedical Engineering
Articles Information
International Journal of Bioinformatics and Biomedical Engineering, Vol.2, No.1, Jan. 2016, Pub. Date: Jan. 9, 2016
Structure Based Drug Designing and In Silico Screening of Monosubstituted 2-{[(E)-{5-Methoxy-1-[4-(trifluoromethyl)phenyl]pentylidene}amino]oxy}Ethanamine (fluvoxamine) as a Potential Drug for Obsessive-Compulsive Disorder
Pages: 1-7 Views: 2743 Downloads: 1085
Authors
[01] I. E. Otuokere, Department of Chemistry, Michael Okpara University of Agriculture, Umudike, Nigeria.
[02] F. J. Amaku, Department of Chemistry, Michael Okpara University of Agriculture, Umudike, Nigeria.
[03] K. K. Igwe, Department of Vet. Biochemistry and Pharmacology, Michael Okpara University of Agriculture, Umudike, Nigeria.
Abstract
2-{[(E)-{5-Methoxy-1-[4-(trifluoromethyl)phenyl]pentylidene}amino]oxy}ethanamine (fluvoxamine)is a sigma-1 receptor (σ1R), agonist used primarily for the treatment of obsessive-compulsive disorder (OCD). We carried out molecular docking for ten analogues structurally diverse 2-{[(E)-{5-Methoxy-1-[4-(trifluoromethyl)phenyl]pentylidene}amino]oxy}ethanamine (fluvoxamine) with σ1 receptors using patchdock and firedock online docking server. Extensive structure activity relationship work was carried out with these molecules, compared with the non-substituted fluvoxamine by performing the docking studies on crystal structure of σ1 receptors (PDB ID: 1AGN). These molecules were designed by substituting NH2 group in fluvoxamine with different chemical groups. The scoring function (empirical binding free energy) of the firedock was used to estimate the free binding energy of the protein-ligand complex. The binding energy of fluvoxamine/σ1 receptorswas -31.73 kcal/mol. CONH2, CH2CH3, CN, NO2, COOH, SO2NH2 and C6H5 analogues lead to a decrease in the binding affinity, meaning that, they have better functional activity. The free binding energies were higher in CF3, CH3 and NO2 analogues, meaning that, they have lesser functional activity. These results clearly indicated that the new agonist have very good binding affinity towards σ1 receptors like fluvoxamine. Synthesis and pre-clinical studies of these monosubstituted derivatives with σ1 receptorsis recommended.
Keywords
Fluvoxamine, Receptors, Docking, Obsessive-Compulsive Disorder
References
[01] FDA Advisory Committee Recommends Luvox (Fluvoxamine) Tablets for Obsessive Compulsive Disorder, PRNewswire, 1993.
[02] Karen, J. and McClellan, D. P. F. (2000). Fluvoxamine. An Updated Review of its Use in the Management of Adults with Anxiety Disorders. Adis Drug Evaluation60 (4): 925–954.
[03] Stahl, S. (2009). Stahl's Essential Psychopharmacology: The Prescriber's Guide. Cambridge University Press. New York, NY. 215.
[04] Kwasucki, J., Stepień, A., Maksymiuk, G., Olbrych-Karpińska, B. (2002). Evaluation of analgesic action of fluvoxamine compared with efficacy of imipramine and tramadol for treatment of sciatica—open trial. Wiadomości Lekarskie55 (1-2): 42–50.
[05] Schreiber, S. and Pick, C.G. (2006). From selective to highly selective SSRIs: A comparison of the antinociceptive properties of fluoxetine, fluvoxamine, citalopram and escitalopram. European Neuropsychopharmacology 16 (6): 464–468.
[06] Coquoz, D., Porchet, H.C., Dayer, P. (1993). Central analgesic effects of desipramine, fluvoxamine, and moclobemide after single oral dosing: a study in healthy volunteers. Clinical Pharmacology and Therapeutics 54 (3): 339–344.
[07] Ritsner, M.S. (2013). Polypharmacy in Psychiatry Practice, I. Springer Science + Business Media, Dordrecht. 1, 12.
[08] Hindmarch, I. and Hashimoto, K (2010). Cognition and depression: the effects of fluvoxamine, a sigma-1 receptor agonist, reconsidered. Human Psychopharmacology: Clinical and Experimental 25 (3): 193–200.
[09] Hayashi, T. andSu, T.P. (2007). Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca2+ signaling and cell survival. Cell,131 (3): 596–610.
[10] Kekuda, R., Prasad, P.D., Fei, Y.J., Leibach, F.H. and Ganapathy, V. (1996). Cloning and functional expression of the human type 1 sigma receptor (hSigmaR1). Biochemical and Biophysical Research Communications 229 (2): 553–558.
[11] Prasad, P.D., Li, H.W., Fei, Y.J., Ganapathy, M.E., Fujita, T., Plumley, L.H., Yang-Feng, T.L., Leibach, F.H. and Ganapathy, V. (1998). Exon-intron structure, analysis of promoter region, and chromosomal localization of the human type 1 sigma receptor gene. Journal of Neurochemistry70 (2): 443–451.
[12] Weissman, A.D., Su, T.P., Hedreen, J.C., London, E.D. (1988). Sigma receptors in post-mortem human brains. The Journal of Pharmacology and Experimental Therapeutics 247 (1): 29–33.
[13] Guitart, X., Codony, X. and Monroy, X. (2004). Sigma receptors: biology and therapeutic potential. Psychopharmacology 174 (3): 301–319.
[14] Su, T.P. and Hayashi, T. (2003). Understanding the molecular mechanism of sigma-1 receptors: towards a hypothesis that sigma-1 receptors are intracellular amplifiers for signal transduction. Current Medicinal Chemistry, 10 (20): 2073–2080.
[15] Leroy, D., Kajava, A.V., Frei, C., Gasser, S.M., (2001). Analysis of etoposide binding to subdomain of human DNA topoisomerase II α in the absence of DNA, Biochemistry 40, 1624–1634.
[16] Dixon, J.S., Blaney, J.M., (1998). Docking: predicting the structure and binding affinity of ligand–receptor complexes; in Designing bioactive molecules: three-dimensional techniquesand applications (eds) Martin, Y.C., Willet, P., Washington DC: American Chemical Society. 175–179
[17] Dipankar, S., Deeptak, V., Pradeep, K.N. (2007). Docking mode of delvardine and its analogues into the p66 domain of HIV-1 reverse transcriptase: screening using molecular mechanics generalized born/surface area and absorption, distribution, metabolism and excretion properties, J. Biosci. 32(7): 1307–1316.
[18] http://www.rcsb.org
[19] Thompson, M.A., 2007. ArgusLab 4.0, Planaria Software LLC, Seattle, WA. http://www.arguslab.com
[20] Duhovny, D., Nussinov, R., Wolfson, H.J. (2002). Efficient Unbound Docking of Rigid Molecules. In Gusfield et al., Ed. Proceedings of the 2'nd Workshop on Algorithms in Bioinformatics (WABI), Springer Verlag, Rome, Italy, Lecture Notes in Computer Science, 2452, 185-200.
[21] Mashiach, E., Schneidman-Duhovny, D., Andrusier, N., Nussinov, R., Woifson, H.J., (2008). FireDock a webserver for fast interaction refinement in molecular docking, Nucleic Acid Res, 36, 229–292.
[22] Andrusier, N., Nussinov, R., Wolfson, H.J., 2007. FireDock: fast interaction refinement in molecular docking, Proteins, 69(1), 139–159.
[23] http://www.clcbio.com
[24] Jayaram, B., Tanya, S., Goutam, M., Abhinav, M., Shashank, S.,Vandana, S., (2012). Sanjeevini: a freely accessible web-server for target directed lead molecule discovery, BMC Bioinformatics,13, S7.
[25] Cramer, G.M., Ford, R.A.,Hall, R.L. (1978). Estimation of toxic hazard--a decision tree approach. Food and Cosmetics Toxicology 16: 255-276.
[26] Verhaar, H.J.M.,Van Leeuwen C.J. Hermens, J.L.M. (1992). Classifying environmental pollutants. Structure – activity relationships for prediction of aquatic toxicity. Chemosphere25, 471-491.
[27] Lipinski, C.A.(2004). Lead- and drug-like compounds: the rule-of-five revolution". Drug Discovery Today: Technologies 1 (4),337-341.
[28] Munro, I.C., Ford, R.A., Kennepohl, E., Sprenger, J.G. (1996). Correlation of structural class with no-observed effect levels: a proposal for establishing a threshold of concern. Food and Chemical Toxicology34: 829-867.
[29] Preeth, M., Shobana, J., Asnet Mary, .J., Suresh, A., Suresh, V., Senthil Kumar, N. (2010). Structure based drug designing of new acetylcholinesterase inhibitors for alzheimer’s disease, Journal of Bioscience and Technology, 1(4): 162-169.
[30] László, F. and Daniela, L. M. (2015).Possible substitutes for paracetamol: the results of acomprehensive screening based on structural similarityand docking simulation on the surface of enzymes, Farmacia, 63(3): 422–428.
[31] Ranganathan, B. and Rachana V. G. (2012). Design and in silico analysis of ring-a monosubstituted chalcones as potential anti-inflammatory agents, Bulletin of Pharmaceutical Research,2(2): 70–77.
600 ATLANTIC AVE, BOSTON,
MA 02210, USA
+001-6179630233
AIS is an academia-oriented and non-commercial institute aiming at providing users with a way to quickly and easily get the academic and scientific information.
Copyright © 2014 - American Institute of Science except certain content provided by third parties.