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,...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2013-04, Vol.62, p.556-563
Main Authors: da Costa, Jessé Sobieski, Lopes, João Paulo Bizarro, Russowsky, Dennis, Petzhold, Cesar Liberato, Borges, Antonio César de Amorim, Ceschi, Marco Antonio, Konrath, Eduardo, Batassini, Cristiane, Lunardi, Paula Santana, Gonçalves, Carlos Alberto Saraiva
Format: Article
Language:English
Subjects:
Acetylcholinesterase - metabolism
Animals
Butyrylcholinesterase - metabolism
Cholinesterase Inhibitors - chemical synthesis
Cholinesterase Inhibitors - chemistry
Cholinesterase Inhibitors - pharmacology
Dose-Response Relationship, Drug
Humans
Imidazoles - chemistry
Male
Molecular Structure
Rats
Rats, Wistar
Structure-Activity Relationship
Tacrine - chemistry
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Summary: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.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2013.01.029