Donepezil structure-based hybrids as potential multifunctional anti-Alzheimer's drug candidates
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/107711 https://doi.org/10.1080/14756366.2018.1491564 |
Resumo: | A new series of multifunctional hybrids, based on the structure of the donepezil (DNP) drug, have been developed and evaluated as potential anti Alzheimer's disease (AD) agents. The rationale of this study was the conjugation of a benzylpiperidine/benzylpiperazine moiety with derivatives of bioactive heterocyclics (benzimidazole or benzofuran), to mimic the main structure of DNP and to endow the hybrids with additional relevant properties such as inhibition of amyloid beta (Aβ) peptide aggregation, antioxidant activity and metal chelation. Overall, they showed good activity for AChE inhibition (IC50=4.0-30.0 μΜ) and moderate ability for inhibition of Aβ1-42 self-mediated aggregation. The hybrids containing chelating groups showed improvement in the inhibition of Cu-induced Aβ42 aggregation and the antioxidant capacity. Moreover, neuroprotective effects of these compounds were evidenced in neuroblastoma cells after Aβ1-42 induced toxicity. Structure-activity relationship allowed the identification of some promising compounds and the main determinant structural features for the targeted properties. |
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Donepezil structure-based hybrids as potential multifunctional anti-Alzheimer's drug candidatesAlzheimer’s diseasemultipotent drugsdonepezil mimeticsAChE inhibitorsanti-Aβ aggregationAcetylcholinesteraseAlzheimer DiseaseAmyloid beta-PeptidesAntioxidantsCaco-2 CellsCell Line, TumorCell SurvivalCholinesterase InhibitorsDonepezilDose-Response Relationship, DrugHumansIndansModels, MolecularMolecular StructurePiperidinesProtein AggregatesStructure-Activity RelationshipA new series of multifunctional hybrids, based on the structure of the donepezil (DNP) drug, have been developed and evaluated as potential anti Alzheimer's disease (AD) agents. The rationale of this study was the conjugation of a benzylpiperidine/benzylpiperazine moiety with derivatives of bioactive heterocyclics (benzimidazole or benzofuran), to mimic the main structure of DNP and to endow the hybrids with additional relevant properties such as inhibition of amyloid beta (Aβ) peptide aggregation, antioxidant activity and metal chelation. Overall, they showed good activity for AChE inhibition (IC50=4.0-30.0 μΜ) and moderate ability for inhibition of Aβ1-42 self-mediated aggregation. The hybrids containing chelating groups showed improvement in the inhibition of Cu-induced Aβ42 aggregation and the antioxidant capacity. Moreover, neuroprotective effects of these compounds were evidenced in neuroblastoma cells after Aβ1-42 induced toxicity. Structure-activity relationship allowed the identification of some promising compounds and the main determinant structural features for the targeted properties.Taylor & Francis2018-12info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/107711http://hdl.handle.net/10316/107711https://doi.org/10.1080/14756366.2018.1491564eng1475-63661475-6374Piemontese, LucaTomás, DanielHiremathad, AshaCapriati, VitoCandeias, EmanuelCardoso, Sandra M.Chaves, SílviaSantos, M. Améliainfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-28T09:14:04Zoai:estudogeral.uc.pt:10316/107711Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:24:01.905853Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Donepezil structure-based hybrids as potential multifunctional anti-Alzheimer's drug candidates |
title |
Donepezil structure-based hybrids as potential multifunctional anti-Alzheimer's drug candidates |
spellingShingle |
Donepezil structure-based hybrids as potential multifunctional anti-Alzheimer's drug candidates Piemontese, Luca Alzheimer’s disease multipotent drugs donepezil mimetics AChE inhibitors anti-Aβ aggregation Acetylcholinesterase Alzheimer Disease Amyloid beta-Peptides Antioxidants Caco-2 Cells Cell Line, Tumor Cell Survival Cholinesterase Inhibitors Donepezil Dose-Response Relationship, Drug Humans Indans Models, Molecular Molecular Structure Piperidines Protein Aggregates Structure-Activity Relationship |
title_short |
Donepezil structure-based hybrids as potential multifunctional anti-Alzheimer's drug candidates |
title_full |
Donepezil structure-based hybrids as potential multifunctional anti-Alzheimer's drug candidates |
title_fullStr |
Donepezil structure-based hybrids as potential multifunctional anti-Alzheimer's drug candidates |
title_full_unstemmed |
Donepezil structure-based hybrids as potential multifunctional anti-Alzheimer's drug candidates |
title_sort |
Donepezil structure-based hybrids as potential multifunctional anti-Alzheimer's drug candidates |
author |
Piemontese, Luca |
author_facet |
Piemontese, Luca Tomás, Daniel Hiremathad, Asha Capriati, Vito Candeias, Emanuel Cardoso, Sandra M. Chaves, Sílvia Santos, M. Amélia |
author_role |
author |
author2 |
Tomás, Daniel Hiremathad, Asha Capriati, Vito Candeias, Emanuel Cardoso, Sandra M. Chaves, Sílvia Santos, M. Amélia |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Piemontese, Luca Tomás, Daniel Hiremathad, Asha Capriati, Vito Candeias, Emanuel Cardoso, Sandra M. Chaves, Sílvia Santos, M. Amélia |
dc.subject.por.fl_str_mv |
Alzheimer’s disease multipotent drugs donepezil mimetics AChE inhibitors anti-Aβ aggregation Acetylcholinesterase Alzheimer Disease Amyloid beta-Peptides Antioxidants Caco-2 Cells Cell Line, Tumor Cell Survival Cholinesterase Inhibitors Donepezil Dose-Response Relationship, Drug Humans Indans Models, Molecular Molecular Structure Piperidines Protein Aggregates Structure-Activity Relationship |
topic |
Alzheimer’s disease multipotent drugs donepezil mimetics AChE inhibitors anti-Aβ aggregation Acetylcholinesterase Alzheimer Disease Amyloid beta-Peptides Antioxidants Caco-2 Cells Cell Line, Tumor Cell Survival Cholinesterase Inhibitors Donepezil Dose-Response Relationship, Drug Humans Indans Models, Molecular Molecular Structure Piperidines Protein Aggregates Structure-Activity Relationship |
description |
A new series of multifunctional hybrids, based on the structure of the donepezil (DNP) drug, have been developed and evaluated as potential anti Alzheimer's disease (AD) agents. The rationale of this study was the conjugation of a benzylpiperidine/benzylpiperazine moiety with derivatives of bioactive heterocyclics (benzimidazole or benzofuran), to mimic the main structure of DNP and to endow the hybrids with additional relevant properties such as inhibition of amyloid beta (Aβ) peptide aggregation, antioxidant activity and metal chelation. Overall, they showed good activity for AChE inhibition (IC50=4.0-30.0 μΜ) and moderate ability for inhibition of Aβ1-42 self-mediated aggregation. The hybrids containing chelating groups showed improvement in the inhibition of Cu-induced Aβ42 aggregation and the antioxidant capacity. Moreover, neuroprotective effects of these compounds were evidenced in neuroblastoma cells after Aβ1-42 induced toxicity. Structure-activity relationship allowed the identification of some promising compounds and the main determinant structural features for the targeted properties. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-12 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/107711 http://hdl.handle.net/10316/107711 https://doi.org/10.1080/14756366.2018.1491564 |
url |
http://hdl.handle.net/10316/107711 https://doi.org/10.1080/14756366.2018.1491564 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1475-6366 1475-6374 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Taylor & Francis |
publisher.none.fl_str_mv |
Taylor & Francis |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134125926383616 |