Synthesis of tacrine-lophine hybrids via one-pot four component reaction and biological evaluation as acetyl- and butyrylcholinesterase inhibitors

A novel series of tacrine-lophine hybrids was synthesized and tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) with IC50 in the nanomolar concentration scale. The key step is the one-pot four component condensation reaction of 9-aminoalkylamino-1,2,3,...

Descripción completa

Detalles Bibliográficos
Autores: Costa, Jessie Sobieski da, Lopes, João Paulo Bizarro, Russowsky, Dennis, Petzhold, Cesar Liberato, Borges, Antônio César de Amorim, Ceschi, Marco Antonio, Konrath, Eduardo Luis, Batassini, Cristiane, Lunardi, Paula Santana, Goncalves, Carlos Alberto Saraiva
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:Brasil
Institución:Universidade Federal do Rio Grande do Sul (UFRGS)
Repositorio:Repositório Institucional da UFRGS
Idioma:inglés
OAI Identifier:oai:www.lume.ufrgs.br:10183/83620
Acceso en línea:http://hdl.handle.net/10183/83620
Access Level:acceso abierto
Palabra clave:Tacrina
Síntese orgânica
Tacrine
Lophine
Four component reaction
Indium trichloride
AChE inhibitory activity
Descripción
Sumario:A novel series of tacrine-lophine hybrids was synthesized and tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) with IC50 in the nanomolar concentration scale. The key step is the one-pot four component condensation reaction of 9-aminoalkylamino-1,2,3,4- tetrahydroacridines, benzil, different substituted aromatic aldehydes and NH4OAc, using InCl3 as the best catalyst. Tacrine-lophine hybrids were found to be potent and selective inhibitors of cholinesterases. As an extension of the four component approach to tetrasubstituted imidazoles, a new series of bis-(2,4,5- triphenyl-1H-imidazoles) or bis(n)-lophines was tested against AChE and BuChE.