The Electronic Influence on the Active Site-Directed Inhibition of Acetylcholinesterase by N-aryl-Substituted Succinimides

A computational docking approach, in combination withthe Hammett relationship, has been employed to evaluate the electronicinfluence of substituents on ligand binding and the activesite-directed inhibitory potency on acetylcholinesterase using nineN-aryl-substituted succinimides. Our results indicat...

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Detalhes bibliográficos
Autores: J. Alberto Guevara Salazar, Michel Espinoza Fonseca, Delia Quintana Zavala, José G. Trujillo, Hiram I. Beltrán, José Correa Basurto
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2007
País:México
Recursos:Instituto Politécnico Nacional
Repositorio:Redalyc-IPN
OAI Identifier:oai:redalyc.org:47551410
Acesso em linha:https://www.redalyc.org/articulo.oa?id=47551410
Access Level:acceso abierto
Palavra-chave:Multidisciplinaria (Ciencias Naturales y Exactas)
aryl
Docking
substituted
succinimides
Acetylcholinesterase
Descrição
Resumo:A computational docking approach, in combination withthe Hammett relationship, has been employed to evaluate the electronicinfluence of substituents on ligand binding and the activesite-directed inhibitory potency on acetylcholinesterase using nineN-aryl-substituted succinimides. Our results indicate that electronwithdrawinggroups attached to benzene moiety of the compoundsfavor the inhibitory potency while electron-donating groups do not.This fact was confirmed by performing kinetic experiments on acetylcholinesterasefrom Electrophorus electricus; the experimentsshowed that para-substituted-NO2 compound inhibits better thanpara-substituted-OMe and –H derivatives. This approach may be usefulfor the rationalization of drugs design, as well as the mechanismof the active site.