title: Novel series of tacrine-tianeptine hybrids: Synthesis, cholinesterase inhibitory activity, S100B secretion and a molecular modeling approach.
abstract: Tianeptine was linked to various 9-aminoalkylamino-1,2,3,4-tetrahydroacridines using EDC·HCl/HOBt to afford a series of tacrine-tianeptine hybrids. The hybrids were tested for their ability to inhibit AChE and BuChE and IC50 values in the nanomolar concentration scale were obtained. AChE molecular modeling studies of these hybrids indicated that tacrine moiety interacts in the bottom of the gorge with the catalytic active site (CAS) while tianeptine binds to peripheral anionic site (PAS). Furthermore, the compounds 2g and 2e were able to reduce the in vitro basal secretion of S100B, suggesting its therapeutic action in some cases or stages of Alzheimer's disease.
authors.affiliation: Instituto de Química, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, Campus do Vale, 91501-970, Porto Alegre, RS, Brazil. Electronic address: mceschi@iq.ufrgs.br.
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Ceschi
authors.affiliation: Instituto de Química, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, Campus do Vale, 91501-970, Porto Alegre, RS, Brazil.
authors.forename: Jessie Sobieski
authors.initials: JS
authors.lastname: da Costa
authors.affiliation: Instituto de Química, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, Campus do Vale, 91501-970, Porto Alegre, RS, Brazil.
authors.forename: João Paulo Bizarro
authors.initials: JPB
authors.lastname: Lopes
authors.affiliation: Instituto de Química, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, Campus do Vale, 91501-970, Porto Alegre, RS, Brazil.
authors.forename: Viktor Saraiva
authors.initials: VS
authors.lastname: Câmara
authors.affiliation: Instituto de Química, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, Campus do Vale, 91501-970, Porto Alegre, RS, Brazil.
authors.forename: Leandra Franciscato
authors.initials: LF
authors.lastname: Campo
authors.affiliation: Instituto de Química, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, Campus do Vale, 91501-970, Porto Alegre, RS, Brazil.
authors.forename: Antonio César de Amorim
authors.initials: ACA
authors.lastname: Borges
authors.affiliation: Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, Prédio Anexo, 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Carlos Alberto Saraiva
authors.initials: CAS
authors.lastname: Gonçalves
authors.affiliation: Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, Prédio Anexo, 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Daniela Fraga
authors.initials: DF
authors.lastname: de Souza
authors.affiliation: Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av Ipiranga, 2752, Santana, 90610000, Porto Alegre, RS, Brazil.
authors.forename: Eduardo Luis
authors.initials: EL
authors.lastname: Konrath
authors.affiliation: Laboratório Nacional De Computação Científica-LNCC, Av. Getulio Vargas, 333, Petrópolis, 25651-075, RJ, Brazil.
authors.forename: Ana Luiza Martins
authors.initials: ALM
authors.lastname: Karl
authors.affiliation: Laboratório Nacional De Computação Científica-LNCC, Av. Getulio Vargas, 333, Petrópolis, 25651-075, RJ, Brazil.
authors.forename: Isabella Alvim
authors.initials: IA
authors.lastname: Guedes
authors.affiliation: Laboratório Nacional De Computação Científica-LNCC, Av. Getulio Vargas, 333, Petrópolis, 25651-075, RJ, Brazil. Electronic address: dardenne@lncc.br.
authors.forename: Laurent Emmanuel
authors.initials: LE
authors.lastname: Dardenne
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D060326:Chemistry Techniques, Synthetic; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D004593:Electrophorus; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008958:Models, Molecular; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D013619:Tacrine / Q000737:chemistry*; D013841:Thiazepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D064568:S100 Calcium Binding Protein beta Subunit; D013841:Thiazepines; C050504:tianeptine; D013619:Tacrine; D007770:L-Lactate Dehydrogenase; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: AChE; BuChE; Coupling reaction; Molecular modeling; S100B secretion; Tacrine; Tianeptine