Neonicotinic analogues: Selective antagonists for α4β2 nicotinic acetylcholine receptors

Simple item page
dc.contributor.authorFaundez-Parraguez, Manuel
dc.contributor.authorFarias-Rabelo, Nicolas
dc.contributor.authorPablo Gonzalez-Gutierrez, Juan
dc.contributor.authorEtcheverry-Berrios, Alvaro
dc.contributor.authorAlzate-Morales, Jans
dc.contributor.authorAdasme-Carreno, Francisco
dc.contributor.authorVaras, Rodrigo
dc.contributor.authorBermudez, Isabel
dc.contributor.authorIturriaga-Vasquez, Patricio
dc.date.accessioned2025-01-24T00:04:03Z
dc.date.available2025-01-24T00:04:03Z
dc.date.issued2013
dc.description.abstractNicotine is an agonist of nicotinic acetylcholine receptors (nAChRs) that has been extensively used as a template for the synthesis of alpha 4 beta 2-preferring nAChRs. Here, we used the N-methyl-pyrrolidine moiety of nicotine to design and synthesise novel alpha 4 beta 2-preferring neonicotinic ligands. We increased the distance between the basic nitrogen and aromatic group of nicotine by introducing an ester functionality that also mimics acetylcholine (Fig. 2). Additionally, we introduced a benzyloxy group linked to the benzoyl moiety. Although the neonicotinic compounds fully inhibited binding of both [alpha-I-125]bungarotoxin to human alpha 7 nAChRs and [H-3]cytisine to human alpha 4 beta 2 nAChRs, they were markedly more potent at displacing radioligand binding to human alpha 4 beta 2 nAChRs than to alpha 7 nAChRs. Functional assays showed that the neonicotinic compounds behave as antagonists at alpha 4 beta 2 and alpha 4 beta 2 alpha 5 nAChRs. Substitutions on the aromatic ring of the compounds produced compounds that displayed marked selectivity for alpha 4 beta 2 or alpha 4 beta 2 alpha 5 nAChRs. Docking of the compounds on homology models of the agonist binding site at the alpha 4/beta 2 subunit interfaces of alpha 4 beta 2 nAChRs suggested the compounds inhibit function of this nAChR type by binding the agonist binding site. (C) 2013 Elsevier Ltd. All rights reserved.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.bmc.2013.03.024
dc.identifier.eissn1464-3391
dc.identifier.issn0968-0896
dc.identifier.urihttps://doi.org/10.1016/j.bmc.2013.03.024
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/101783
dc.identifier.wosidWOS:000318318700003
dc.issue.numero10
dc.language.isoen
dc.pagina.final2694
dc.pagina.inicio2687
dc.revistaBioorganic & medicinal chemistry
dc.rightsacceso restringido
dc.subjectNicotinic acetylcholine receptors
dc.subjectStructure-activity relationships
dc.subjectFunctional and affinities
dc.subjectAntagonism
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleNeonicotinic analogues: Selective antagonists for α4β2 nicotinic acetylcholine receptors
dc.typeartículo
dc.volumen21
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
Files
Collections
Artículos de revistas