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
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[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.
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.
Fluvoxamine, Receptors, Docking, Obsessive-Compulsive Disorder
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