Derivatives of Tenuazonic Acid as Potential New Multi-Target Anti-Alzheimer's Disease Agents
Autor(a) principal: | |
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Data de Publicação: | 2021 |
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/10316/103766 https://doi.org/10.3390/biom11010111 |
Resumo: | Alzheimer's disease (AD) is generally recognized as a multifactorial neurodegenerative pathology with an increasing impact on society. Tenuazonic acid (TA) is a natural compound that was recently identified as a potential multitarget ligand with anti-cholinesterase, anti-amyloidogenic and antioxidant activities. Using its structure as a chemical scaffold, we synthesized and evaluated new derivatives (1-5), including tenuazonic-donepezil (TA-DNP) hybrids (4 and 5) due to the clinical importance of the anti-AD drug donepezil. These novel compounds all achieved activity in the micromolar range towards all selected targets and demonstrated to be potentially orally absorbed. Moreover, a selected compound (1) was further investigated as a chelating agent towards copper (II), zinc (II) and iron (III) and showed good chelating ability (pFe = 16.6, pCu = 11.6, pZn = 6.0 at pH 7.4). Therefore, the TA motif can be considered an interesting building block in the search for innovative multi-functional anti-neurodegenerative drugs, as exemplified by hybrid 5, a promising non-cytotoxic lead compound adequate for the early stages of AD, and capable of ameliorating the oxidative status of SH-SY5Y human neuroblastoma cells. |
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Derivatives of Tenuazonic Acid as Potential New Multi-Target Anti-Alzheimer's Disease AgentsAlzheimer’s diseasetenuazonic aciddonepezilneurodegenerativemetal chelationmultifunctional drugsacetylcholinesteraseantioxidantamyloidAlzheimer DiseaseAmyloid beta-PeptidesCell Line, TumorCell SurvivalCholinesterase InhibitorsDonepezilFree Radical ScavengersHumansHydrogen-Ion ConcentrationMetalsMolecular Docking SimulationNeuroprotectionNeuroprotective AgentsProtein AggregatesSpectrophotometryTenuazonic AcidAlzheimer's disease (AD) is generally recognized as a multifactorial neurodegenerative pathology with an increasing impact on society. Tenuazonic acid (TA) is a natural compound that was recently identified as a potential multitarget ligand with anti-cholinesterase, anti-amyloidogenic and antioxidant activities. Using its structure as a chemical scaffold, we synthesized and evaluated new derivatives (1-5), including tenuazonic-donepezil (TA-DNP) hybrids (4 and 5) due to the clinical importance of the anti-AD drug donepezil. These novel compounds all achieved activity in the micromolar range towards all selected targets and demonstrated to be potentially orally absorbed. Moreover, a selected compound (1) was further investigated as a chelating agent towards copper (II), zinc (II) and iron (III) and showed good chelating ability (pFe = 16.6, pCu = 11.6, pZn = 6.0 at pH 7.4). Therefore, the TA motif can be considered an interesting building block in the search for innovative multi-functional anti-neurodegenerative drugs, as exemplified by hybrid 5, a promising non-cytotoxic lead compound adequate for the early stages of AD, and capable of ameliorating the oxidative status of SH-SY5Y human neuroblastoma cells.MDPI AG2021-01-15info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/103766http://hdl.handle.net/10316/103766https://doi.org/10.3390/biom11010111eng2218-273XPoliseno, VivianaChaves, SílviaBrunetti, LeonardoLoiodice, FulvioCarrieri, AntonioLaghezza, AntonioTortorella, PaoloMagalhães, João D.Cardoso, Sandra M.Santos, M. AméliaPiemontese, Lucainfo: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:RCAAP2022-11-25T21:40:53Zoai:estudogeral.uc.pt:10316/103766Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:20:32.766413Repositório 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 |
Derivatives of Tenuazonic Acid as Potential New Multi-Target Anti-Alzheimer's Disease Agents |
title |
Derivatives of Tenuazonic Acid as Potential New Multi-Target Anti-Alzheimer's Disease Agents |
spellingShingle |
Derivatives of Tenuazonic Acid as Potential New Multi-Target Anti-Alzheimer's Disease Agents Poliseno, Viviana Alzheimer’s disease tenuazonic acid donepezil neurodegenerative metal chelation multifunctional drugs acetylcholinesterase antioxidant amyloid Alzheimer Disease Amyloid beta-Peptides Cell Line, Tumor Cell Survival Cholinesterase Inhibitors Donepezil Free Radical Scavengers Humans Hydrogen-Ion Concentration Metals Molecular Docking Simulation Neuroprotection Neuroprotective Agents Protein Aggregates Spectrophotometry Tenuazonic Acid |
title_short |
Derivatives of Tenuazonic Acid as Potential New Multi-Target Anti-Alzheimer's Disease Agents |
title_full |
Derivatives of Tenuazonic Acid as Potential New Multi-Target Anti-Alzheimer's Disease Agents |
title_fullStr |
Derivatives of Tenuazonic Acid as Potential New Multi-Target Anti-Alzheimer's Disease Agents |
title_full_unstemmed |
Derivatives of Tenuazonic Acid as Potential New Multi-Target Anti-Alzheimer's Disease Agents |
title_sort |
Derivatives of Tenuazonic Acid as Potential New Multi-Target Anti-Alzheimer's Disease Agents |
author |
Poliseno, Viviana |
author_facet |
Poliseno, Viviana Chaves, Sílvia Brunetti, Leonardo Loiodice, Fulvio Carrieri, Antonio Laghezza, Antonio Tortorella, Paolo Magalhães, João D. Cardoso, Sandra M. Santos, M. Amélia Piemontese, Luca |
author_role |
author |
author2 |
Chaves, Sílvia Brunetti, Leonardo Loiodice, Fulvio Carrieri, Antonio Laghezza, Antonio Tortorella, Paolo Magalhães, João D. Cardoso, Sandra M. Santos, M. Amélia Piemontese, Luca |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Poliseno, Viviana Chaves, Sílvia Brunetti, Leonardo Loiodice, Fulvio Carrieri, Antonio Laghezza, Antonio Tortorella, Paolo Magalhães, João D. Cardoso, Sandra M. Santos, M. Amélia Piemontese, Luca |
dc.subject.por.fl_str_mv |
Alzheimer’s disease tenuazonic acid donepezil neurodegenerative metal chelation multifunctional drugs acetylcholinesterase antioxidant amyloid Alzheimer Disease Amyloid beta-Peptides Cell Line, Tumor Cell Survival Cholinesterase Inhibitors Donepezil Free Radical Scavengers Humans Hydrogen-Ion Concentration Metals Molecular Docking Simulation Neuroprotection Neuroprotective Agents Protein Aggregates Spectrophotometry Tenuazonic Acid |
topic |
Alzheimer’s disease tenuazonic acid donepezil neurodegenerative metal chelation multifunctional drugs acetylcholinesterase antioxidant amyloid Alzheimer Disease Amyloid beta-Peptides Cell Line, Tumor Cell Survival Cholinesterase Inhibitors Donepezil Free Radical Scavengers Humans Hydrogen-Ion Concentration Metals Molecular Docking Simulation Neuroprotection Neuroprotective Agents Protein Aggregates Spectrophotometry Tenuazonic Acid |
description |
Alzheimer's disease (AD) is generally recognized as a multifactorial neurodegenerative pathology with an increasing impact on society. Tenuazonic acid (TA) is a natural compound that was recently identified as a potential multitarget ligand with anti-cholinesterase, anti-amyloidogenic and antioxidant activities. Using its structure as a chemical scaffold, we synthesized and evaluated new derivatives (1-5), including tenuazonic-donepezil (TA-DNP) hybrids (4 and 5) due to the clinical importance of the anti-AD drug donepezil. These novel compounds all achieved activity in the micromolar range towards all selected targets and demonstrated to be potentially orally absorbed. Moreover, a selected compound (1) was further investigated as a chelating agent towards copper (II), zinc (II) and iron (III) and showed good chelating ability (pFe = 16.6, pCu = 11.6, pZn = 6.0 at pH 7.4). Therefore, the TA motif can be considered an interesting building block in the search for innovative multi-functional anti-neurodegenerative drugs, as exemplified by hybrid 5, a promising non-cytotoxic lead compound adequate for the early stages of AD, and capable of ameliorating the oxidative status of SH-SY5Y human neuroblastoma cells. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-01-15 |
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/10316/103766 http://hdl.handle.net/10316/103766 https://doi.org/10.3390/biom11010111 |
url |
http://hdl.handle.net/10316/103766 https://doi.org/10.3390/biom11010111 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2218-273X |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
MDPI AG |
publisher.none.fl_str_mv |
MDPI AG |
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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1799134097811963904 |