Investigation of the Enantioselectivity of Acetylcholinesterase and Butyrylcholinesterase upon Inhibition by Tacrine-iminosugar Heterodimers

The copper-catalysed azide-alkyne cycloaddition was applied to prepare three enantiomeric pairs of heterodimers containing a tacrine residue and a 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) or 1,4-dideoxy-1,4-imino-L-arabinitol (LAB) moiety held together via linkers of variable lengths containing a 1,...

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Autores: Vaaland, I. Caroline, López López, Óscar, Puerta, Adrián, Fernandes, Miguel X., Padrón, José M., Fernández-Bolaños Guzmán, José María, Sydnes, Magne O., Lindback, Emil
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/148866
Acceso en línea:https://hdl.handle.net/11441/148866
https://doi.org/10.1080/14756366.2022.2150762
Access Level:acceso abierto
Palabra clave:Alzheimer’s disease
Cholinesterases
Enantiomers
Inhibitors
Modelling
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repository_id_str
spelling Investigation of the Enantioselectivity of Acetylcholinesterase and Butyrylcholinesterase upon Inhibition by Tacrine-iminosugar HeterodimersVaaland, I. CarolineLópez López, ÓscarPuerta, AdriánFernandes, Miguel X.Padrón, José M.Fernández-Bolaños Guzmán, José MaríaSydnes, Magne O.Lindback, EmilAlzheimer’s diseaseCholinesterasesEnantiomersInhibitorsModellingThe copper-catalysed azide-alkyne cycloaddition was applied to prepare three enantiomeric pairs of heterodimers containing a tacrine residue and a 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) or 1,4-dideoxy-1,4-imino-L-arabinitol (LAB) moiety held together via linkers of variable lengths containing a 1,2,3-triazole ring and 3, 4, or 7 CH2 groups. The heterodimers were tested as inhibitors of butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE). The enantiomeric heterodimers with the longest linkers exhibited the highest inhibition potencies for AChE (IC50 = 9.7 nM and 11 nM) and BuChE (IC50 = 8.1 nM and 9.1 nM). AChE exhibited the highest enantioselectivity (ca. 4-fold). The enantiomeric pairs of the heterodimers were found to be inactive (GI50 > 100 µM), or to have weak antiproliferative properties (GI50 = 84–97 µM) against a panel of human cancer cells.Gobierno de España PID2020-116460RB-I00, PID2021-123059OB-I00European Commission. Fondo Social Europeo TESIS2020010055Taylor & FrancisQuímica OrgánicaGobierno de EspañaEuropean Commission. Fondo Social Europeo (FSO)2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/148866https://doi.org/10.1080/14756366.2022.2150762reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésJournal of Enzyme Inhibition and Medicinal Chemistry, 38 (1), 349-360.PID2020-116460RB-I00PID2021-123059OB-I00TESIS2020010055https://doi.org/10.1080/14756366.2022.2150762info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1488662026-06-17T12:51:07Z
dc.title.none.fl_str_mv Investigation of the Enantioselectivity of Acetylcholinesterase and Butyrylcholinesterase upon Inhibition by Tacrine-iminosugar Heterodimers
title Investigation of the Enantioselectivity of Acetylcholinesterase and Butyrylcholinesterase upon Inhibition by Tacrine-iminosugar Heterodimers
spellingShingle Investigation of the Enantioselectivity of Acetylcholinesterase and Butyrylcholinesterase upon Inhibition by Tacrine-iminosugar Heterodimers
Vaaland, I. Caroline
Alzheimer’s disease
Cholinesterases
Enantiomers
Inhibitors
Modelling
title_short Investigation of the Enantioselectivity of Acetylcholinesterase and Butyrylcholinesterase upon Inhibition by Tacrine-iminosugar Heterodimers
title_full Investigation of the Enantioselectivity of Acetylcholinesterase and Butyrylcholinesterase upon Inhibition by Tacrine-iminosugar Heterodimers
title_fullStr Investigation of the Enantioselectivity of Acetylcholinesterase and Butyrylcholinesterase upon Inhibition by Tacrine-iminosugar Heterodimers
title_full_unstemmed Investigation of the Enantioselectivity of Acetylcholinesterase and Butyrylcholinesterase upon Inhibition by Tacrine-iminosugar Heterodimers
title_sort Investigation of the Enantioselectivity of Acetylcholinesterase and Butyrylcholinesterase upon Inhibition by Tacrine-iminosugar Heterodimers
dc.creator.none.fl_str_mv Vaaland, I. Caroline
López López, Óscar
Puerta, Adrián
Fernandes, Miguel X.
Padrón, José M.
Fernández-Bolaños Guzmán, José María
Sydnes, Magne O.
Lindback, Emil
author Vaaland, I. Caroline
author_facet Vaaland, I. Caroline
López López, Óscar
Puerta, Adrián
Fernandes, Miguel X.
Padrón, José M.
Fernández-Bolaños Guzmán, José María
Sydnes, Magne O.
Lindback, Emil
author_role author
author2 López López, Óscar
Puerta, Adrián
Fernandes, Miguel X.
Padrón, José M.
Fernández-Bolaños Guzmán, José María
Sydnes, Magne O.
Lindback, Emil
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Química Orgánica
Gobierno de España
European Commission. Fondo Social Europeo (FSO)
dc.subject.none.fl_str_mv Alzheimer’s disease
Cholinesterases
Enantiomers
Inhibitors
Modelling
topic Alzheimer’s disease
Cholinesterases
Enantiomers
Inhibitors
Modelling
description The copper-catalysed azide-alkyne cycloaddition was applied to prepare three enantiomeric pairs of heterodimers containing a tacrine residue and a 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) or 1,4-dideoxy-1,4-imino-L-arabinitol (LAB) moiety held together via linkers of variable lengths containing a 1,2,3-triazole ring and 3, 4, or 7 CH2 groups. The heterodimers were tested as inhibitors of butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE). The enantiomeric heterodimers with the longest linkers exhibited the highest inhibition potencies for AChE (IC50 = 9.7 nM and 11 nM) and BuChE (IC50 = 8.1 nM and 9.1 nM). AChE exhibited the highest enantioselectivity (ca. 4-fold). The enantiomeric pairs of the heterodimers were found to be inactive (GI50 > 100 µM), or to have weak antiproliferative properties (GI50 = 84–97 µM) against a panel of human cancer cells.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/148866
https://doi.org/10.1080/14756366.2022.2150762
url https://hdl.handle.net/11441/148866
https://doi.org/10.1080/14756366.2022.2150762
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Journal of Enzyme Inhibition and Medicinal Chemistry, 38 (1), 349-360.
PID2020-116460RB-I00
PID2021-123059OB-I00
TESIS2020010055
https://doi.org/10.1080/14756366.2022.2150762
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Taylor & Francis
publisher.none.fl_str_mv Taylor & Francis
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301629

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