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

• Autor(a) principal: Costa, Jessie Sobieski da
• Data de Publicação: 2013
• Outros Autores: 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 documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRGS
• Texto Completo: http://hdl.handle.net/10183/83620
• topic: Tacrina; Síntese orgânica; Tacrine; Lophine; Four component reaction; Indium trichloride; AChE inhibitory activity

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.