Estudos de modelagem molecular de compostos bioativos frente ao receptor nicotínico de acetilcolina do subtipo alfa4beta2

• Autor(a) principal: Batista, Victor de Sousa [UNESP]
• Data de Publicação: 2016
• Tipo de documento: Trabalho de conclusão de curso
• Idioma: por
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://hdl.handle.net/11449/155534; http://www.athena.biblioteca.unesp.br/exlibris/bd/capelo/2017-06-19/000885534.pdf
• topic: Química farmacêutica; Ligantes (Bioquímica); Compostos bioativos; Reconhecimento molecular; Receptores nicotínicos; Nicotinic receptors

Neuronal nicotinic acetylcholine receptors (nAChRs) are pentameric transmembrane ion channels located in the central nervous system (CNS) that open and allow the flow of some ions through the action of the endogenous neurotransmitter acetylcholine or exogenous molecules, such as nicotine. They are involved in several CNS disorders such as Alzheimer's, Parkinson's, epilepsy, schizophrenia, among other highly debilitating diseases, as well as mediating the mechanism of nicotine addiction. Given the great number of diseases in which they are involved, it is clear the importance of the rational design of novel compounds that target them. The nAChRs present a great structural diversity, with several subunits that can be combined in different ways to form an ion channel with different properties. The nAChRs subtypes more expressed in the CNS are the α3β4, α7 and α4β2 subtypes, the latter being the focus of this work. Until recently, there were no defined crystallographic structures for nAChRs of the α4β2 subtype of the human species, so studies aimed for the planning of new drug candidates were performed using homology models that are not always able to predict the real interactions between the ligands and their receptor. With the recent elucidation of the receptor's three-dimensional crystal, the process of rational design of these bioactive substances becomes more effective. In this context, we used the crystallographic structure of α4β2 subtype nAChRs for molecular docking studies using the GOLD® program and a set of ligands obtained from the literature in order to better understand the interactions involved in the ligand-receptor complexes formed and evaluate the predictive capability of the computational model.