Novel tacrine-benzofuran hybrids as potential multi-target drug candidates for the treatment of Alzheimer's Disease
Autor(a) principal: | |
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Data de Publicação: | 2020 |
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/10316/106286 https://doi.org/10.1080/14756366.2019.1689237 |
Resumo: | Pursuing the widespread interest on multi-target drugs to combat Alzheimer´s disease (AD), a new series of hybrids was designed and developed based on the repositioning of the well-known acetylcholinesterase (AChE) inhibitor, tacrine (TAC), by its coupling to benzofuran (BF) derivatives. The BF framework aims to endow the conjugate molecules with ability for inhibition of AChE (bimodal way) and of amyloid-beta peptide aggregation, besides providing metal (Fe, Cu) chelating ability and concomitant extra anti-oxidant activity, for the hybrids with hydroxyl substitution. The new TAC-BF conjugates showed very good activity for AChE inhibition (sub-micromolar range) and good capacity for the inhibition of self- and Cu-mediated Aβ aggregation, with dependence on the linker size and substituent groups of each main moiety. Neuroprotective effects were also found for the compounds through viability assays of neuroblastoma cells, after Aβ1-42 induced toxicity. Structure-activity relationship analysis provides insights on the best structural parameters, to take in consideration for future studies in view of potential applications in AD therapy. |
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Novel tacrine-benzofuran hybrids as potential multi-target drug candidates for the treatment of Alzheimer's DiseaseAlzheimer’s diseasemultitarget drugstacrinebenzofuran hybridsAChE inhibitorsmetal chelatorsAcetylcholinesteraseAlzheimer DiseaseAnimalsBenzofuransCholinesterase InhibitorsDose-Response Relationship, DrugElectrophorusHumansModels, MolecularMolecular StructureNeuroprotective AgentsStructure-Activity RelationshipTacrinePursuing the widespread interest on multi-target drugs to combat Alzheimer´s disease (AD), a new series of hybrids was designed and developed based on the repositioning of the well-known acetylcholinesterase (AChE) inhibitor, tacrine (TAC), by its coupling to benzofuran (BF) derivatives. The BF framework aims to endow the conjugate molecules with ability for inhibition of AChE (bimodal way) and of amyloid-beta peptide aggregation, besides providing metal (Fe, Cu) chelating ability and concomitant extra anti-oxidant activity, for the hybrids with hydroxyl substitution. The new TAC-BF conjugates showed very good activity for AChE inhibition (sub-micromolar range) and good capacity for the inhibition of self- and Cu-mediated Aβ aggregation, with dependence on the linker size and substituent groups of each main moiety. Neuroprotective effects were also found for the compounds through viability assays of neuroblastoma cells, after Aβ1-42 induced toxicity. Structure-activity relationship analysis provides insights on the best structural parameters, to take in consideration for future studies in view of potential applications in AD therapy.Taylor and Francis Ltd2020-12info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/106286http://hdl.handle.net/10316/106286https://doi.org/10.1080/14756366.2019.1689237eng1475-63661475-6374Fancellu, GaiaChand, KaramTomás, DanielOrlandini, ElisabettaPiemontese, LucaSilva, Diana F.Cardoso, 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:RCAAP2023-03-28T20:38:03Zoai:estudogeral.uc.pt:10316/106286Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:22:46.041425Repositório 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 |
Novel tacrine-benzofuran hybrids as potential multi-target drug candidates for the treatment of Alzheimer's Disease |
title |
Novel tacrine-benzofuran hybrids as potential multi-target drug candidates for the treatment of Alzheimer's Disease |
spellingShingle |
Novel tacrine-benzofuran hybrids as potential multi-target drug candidates for the treatment of Alzheimer's Disease Fancellu, Gaia Alzheimer’s disease multitarget drugs tacrinebenzofuran hybrids AChE inhibitors metal chelators Acetylcholinesterase Alzheimer Disease Animals Benzofurans Cholinesterase Inhibitors Dose-Response Relationship, Drug Electrophorus Humans Models, Molecular Molecular Structure Neuroprotective Agents Structure-Activity Relationship Tacrine |
title_short |
Novel tacrine-benzofuran hybrids as potential multi-target drug candidates for the treatment of Alzheimer's Disease |
title_full |
Novel tacrine-benzofuran hybrids as potential multi-target drug candidates for the treatment of Alzheimer's Disease |
title_fullStr |
Novel tacrine-benzofuran hybrids as potential multi-target drug candidates for the treatment of Alzheimer's Disease |
title_full_unstemmed |
Novel tacrine-benzofuran hybrids as potential multi-target drug candidates for the treatment of Alzheimer's Disease |
title_sort |
Novel tacrine-benzofuran hybrids as potential multi-target drug candidates for the treatment of Alzheimer's Disease |
author |
Fancellu, Gaia |
author_facet |
Fancellu, Gaia Chand, Karam Tomás, Daniel Orlandini, Elisabetta Piemontese, Luca Silva, Diana F. Cardoso, Sandra M. Chaves, Sílvia Santos, M. Amélia |
author_role |
author |
author2 |
Chand, Karam Tomás, Daniel Orlandini, Elisabetta Piemontese, Luca Silva, Diana F. Cardoso, Sandra M. Chaves, Sílvia Santos, M. Amélia |
author2_role |
author author author author author author author author |
dc.contributor.author.fl_str_mv |
Fancellu, Gaia Chand, Karam Tomás, Daniel Orlandini, Elisabetta Piemontese, Luca Silva, Diana F. Cardoso, Sandra M. Chaves, Sílvia Santos, M. Amélia |
dc.subject.por.fl_str_mv |
Alzheimer’s disease multitarget drugs tacrinebenzofuran hybrids AChE inhibitors metal chelators Acetylcholinesterase Alzheimer Disease Animals Benzofurans Cholinesterase Inhibitors Dose-Response Relationship, Drug Electrophorus Humans Models, Molecular Molecular Structure Neuroprotective Agents Structure-Activity Relationship Tacrine |
topic |
Alzheimer’s disease multitarget drugs tacrinebenzofuran hybrids AChE inhibitors metal chelators Acetylcholinesterase Alzheimer Disease Animals Benzofurans Cholinesterase Inhibitors Dose-Response Relationship, Drug Electrophorus Humans Models, Molecular Molecular Structure Neuroprotective Agents Structure-Activity Relationship Tacrine |
description |
Pursuing the widespread interest on multi-target drugs to combat Alzheimer´s disease (AD), a new series of hybrids was designed and developed based on the repositioning of the well-known acetylcholinesterase (AChE) inhibitor, tacrine (TAC), by its coupling to benzofuran (BF) derivatives. The BF framework aims to endow the conjugate molecules with ability for inhibition of AChE (bimodal way) and of amyloid-beta peptide aggregation, besides providing metal (Fe, Cu) chelating ability and concomitant extra anti-oxidant activity, for the hybrids with hydroxyl substitution. The new TAC-BF conjugates showed very good activity for AChE inhibition (sub-micromolar range) and good capacity for the inhibition of self- and Cu-mediated Aβ aggregation, with dependence on the linker size and substituent groups of each main moiety. Neuroprotective effects were also found for the compounds through viability assays of neuroblastoma cells, after Aβ1-42 induced toxicity. Structure-activity relationship analysis provides insights on the best structural parameters, to take in consideration for future studies in view of potential applications in AD therapy. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-12 |
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/10316/106286 http://hdl.handle.net/10316/106286 https://doi.org/10.1080/14756366.2019.1689237 |
url |
http://hdl.handle.net/10316/106286 https://doi.org/10.1080/14756366.2019.1689237 |
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 and Francis Ltd |
publisher.none.fl_str_mv |
Taylor and Francis Ltd |
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 |
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1799134115774070784 |