Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/113305
DC Field | Value | Language |
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dc.contributor.author | Vicente-Zurdo, David | - |
dc.contributor.author | Brunetti, Leonardo | - |
dc.contributor.author | Piemontese, Luca | - |
dc.contributor.author | Guedes, Beatriz | - |
dc.contributor.author | Cardoso, Sandra M. | - |
dc.contributor.author | Chavarria, Daniel | - |
dc.contributor.author | Borges, Fernanda | - |
dc.contributor.author | Madrid, Yolanda | - |
dc.contributor.author | Chaves, Sílvia | - |
dc.contributor.author | Santos, M. Amélia | - |
dc.date.accessioned | 2024-02-14T12:54:52Z | - |
dc.date.available | 2024-02-14T12:54:52Z | - |
dc.date.issued | 2023-05-05 | - |
dc.identifier.issn | 1422-0067 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/113305 | - |
dc.description.abstract | With the goal of combating the multi-faceted Alzheimer's disease (AD), a series of Rivastigmine-Benzimidazole (RIV-BIM) hybrids was recently reported by us as multitarget-directed ligands, thanks to their capacity to tackle important hallmarks of AD. In particular, they exhibited antioxidant activity, acted as cholinesterase inhibitors, and inhibited amyloid-β (Aβ) aggregation. Herein, we moved forward in this project, studying their ability to chelate redox-active biometal ions, Cu(II) and Fe(III), with widely recognized roles in the generation of oxidative reactive species and in protein misfolding and aggregation in both AD and Parkinson's disease (PD). Although Cu(II) chelation showed higher efficiency for the positional isomers of series 5 than those of series 4 of the hybrids, the Aβ-aggregation inhibition appears more dependent on their capacity for fibril intercalation than on copper chelation. Since monoamine oxidases (MAOs) are also important targets for the treatment of AD and PD, the capacity of these hybrids to inhibit MAO-A and MAO-B was evaluated, and they showed higher activity and selectivity for MAO-A. The rationalization of the experimental evaluations (metal chelation and MAO inhibition) was supported by computational molecular modeling studies. Finally, some compounds showed also neuroprotective effects in human neuroblastoma (SH-SY5Y cells) upon treatment with 1-methyl-4-phenylpyridinium (MPP+), a neurotoxic metabolite of a Parkinsonian-inducing agent. | pt |
dc.language.iso | eng | pt |
dc.publisher | MDPI | pt |
dc.relation | This work was supported by the Portuguese Fundação para a Ciência e Tecnologia (FCT), through project grants: UIDB/00100/2020, UIDP/00100/2020 (CQE) UIDB/04539/2020, UIDP/04539/2020 (CNC), LA/P/0058/2020 (IMS), UIDB/00081/2020, UIDP/00081/2020 (CIQUP), LA/P/0056/2020 (IMS), PT-OPENSCREEN–NORTE-01-0145-FEDER-085468; the Spanish Ministry of Science and Innovation (PID2020-114714RB-I00), and the Community of Madrid and European funding from FSE and FEDER programs for financial support (S2018/BAA-4393, AVANSECALII- CM). D.V.-Z. acknowledges the Spanish Ministry of Science, Innovation, and Universities for funding through a pre-doctoral grant (FPU18/00573) and the Erasmus+ program for an international fellowship. L.B. was supported by a PD/BD/2020.06543.BD PhD fellowship. | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject | Alzheimer’s disease | pt |
dc.subject | Parkinson’s disease | pt |
dc.subject | rivastigmine hybrids | pt |
dc.subject | metal chelation | pt |
dc.subject | cholinesterases | pt |
dc.subject | monoamine oxidase | pt |
dc.subject | amyloid- aggregation | pt |
dc.subject.mesh | Humans | pt |
dc.subject.mesh | Rivastigmine | pt |
dc.subject.mesh | Ferric Compounds | pt |
dc.subject.mesh | Amyloid beta-Peptides | pt |
dc.subject.mesh | Cholinesterase Inhibitors | pt |
dc.subject.mesh | Monoamine Oxidase | pt |
dc.subject.mesh | Chelating Agents | pt |
dc.subject.mesh | Benzimidazoles | pt |
dc.subject.mesh | Neurodegenerative Diseases | pt |
dc.subject.mesh | Neuroblastoma | pt |
dc.subject.mesh | Alzheimer Disease | pt |
dc.title | Rivastigmine-Benzimidazole Hybrids as Promising Multitarget Metal-Modulating Compounds for Potential Treatment of Neurodegenerative Diseases | pt |
dc.type | article | - |
degois.publication.firstPage | 8312 | pt |
degois.publication.issue | 9 | pt |
degois.publication.title | International Journal of Molecular Sciences | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.3390/ijms24098312 | pt |
degois.publication.volume | 24 | pt |
dc.date.embargo | 2023-05-05 | * |
uc.date.periodoEmbargo | 0 | pt |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.fulltext | Com Texto completo | - |
item.grantfulltext | open | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.openairetype | article | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0002-8171-9062 | - |
crisitem.author.orcid | 0000-0002-2199-0555 | - |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
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