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

Autor: da Costa JS; Instituto de Química, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, Campus do Vale, 91501-970 Porto Alegre - RS, Brazil., Lopes JP, Russowsky D, Petzhold CL, Borges AC, Ceschi MA, Konrath E, Batassini C, Lunardi PS, Gonçalves CA
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2013 Apr; Vol. 62, pp. 556-63. Date of Electronic Publication: 2013 Feb 04.
DOI: 10.1016/j.ejmech.2013.01.029
Abstrakt: 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.
(Copyright © 2013 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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