title: Synthesis of tacrine-lophine hybrids via one-pot four component reaction and biological evaluation as acetyl- and butyrylcholinesterase inhibitors.
abstract: 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.
authors: Instituto de Química, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, Campus do Vale, 91501-970 Porto Alegre - RS, Brazil.
authors: Jessé Sobieski
authors: JS
authors: da Costa
authors: João Paulo Bizarro
authors: JP
authors: Lopes
authors: Dennis
authors: D
authors: Russowsky
authors: Cesar Liberato
authors: CL
authors: Petzhold
authors: Antonio César de Amorim
authors: AC
authors: Borges
authors: Marco Antonio
authors: MA
authors: Ceschi
authors: Eduardo
authors: E
authors: Konrath
authors: Cristiane
authors: C
authors: Batassini
authors: Paula Santana
authors: PS
authors: Lunardi
authors: Carlos Alberto Saraiva
authors: CA
authors: Gonçalves
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013619:Tacrine / Q000737:chemistry*
chemical_list: D002800:Cholinesterase Inhibitors; D007093:Imidazoles; D013619:Tacrine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; C107378:lophine