Designing compounds with probable serotoninergic activity: In silico and in vivo evaluation over a stress model

4^th International Conference on Medicinal Chemistry & Computer Aided Drug Designing

November 02-04, 2015 Atlanta, USA

Laura Ivon P�©rez S�¡nchez, Jos�© Ra�ºl Bahena Herrera, Erik Andrade Jorge, Daniel Ernesto Guevara Aveda�±o and Jos�© G Trujillo Ferrara

Escuela Superior de Medicina, M�©xico

Posters-Accepted Abstracts: Med chem

Abstract :

Both 5HT1A receptor and serotonin transporter SERT have an essential role in the homeostasis of serotonergic pathway. Deregulation of these proteins leads to complex mental disorders, making them an attractive pharmacological target for the development of new antipsychotics or antidepressive drugs. Therefore, elucidate essential interactions for ligand-receptor recognition and the discovery of compounds with affinity over them, is a topic of interest for pharmacology. In this study, we aim for the rational design of a novel series of isoindoline-based molecules with dual action over 5HT1A receptor and SERT. The in silico results suggest that our molecules share the binding mode with serotonin, fluoxetine and vilazodone, interacting with the aminoacid residues ASP116, ILE 113, CYS 187, SER 199 and TRP 35 for 5HT1A receptor, and with TYR95, ILE 172, TYR 176, SER 336, VAL 343 and THR 439 for SERT. Ligands MD20, MD22 and MD1 presents the highest affinity over both receptors; our molecules might be metabolized by CYP450 and they fulfill the Lipinski�s rule of five. A newfangled route of synthesis for the designed molecules was completed with a novel reaction. In vivo open field test in CD1 mice with acute administration of ligand MD1 demonstrated that this molecule presents an interesting anxiogenic-like effect. We propose that the designed drugs are likely to interact with the studied receptors. Future experiments will be performed in order to determine in vitro and in vivo behavior of this molecules and their metabolites.

Biography :

Email: lauramagenta95@hotmail.com