Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/103683
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Chavarria, Daniel | - |
dc.contributor.author | Da Silva, Ophelie | - |
dc.contributor.author | Benfeito, Sofia | - |
dc.contributor.author | Barreiro, Sandra | - |
dc.contributor.author | Garrido, Jorge | - |
dc.contributor.author | Cagide, Fernando | - |
dc.contributor.author | Soares, Pedro | - |
dc.contributor.author | Remião, Fernando | - |
dc.contributor.author | Brazzolotto, Xavier | - |
dc.contributor.author | Nachon, Florian | - |
dc.contributor.author | Oliveira, Paulo J. | - |
dc.contributor.author | Dias, José | - |
dc.contributor.author | Borges, Fernanda | - |
dc.date.accessioned | 2022-11-21T11:01:21Z | - |
dc.date.available | 2022-11-21T11:01:21Z | - |
dc.date.issued | 2021-02-23 | - |
dc.identifier.issn | 2076-3921 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/103683 | - |
dc.description.abstract | Neurotransmitter depletion and mitochondrial dysfunction are among the multiple pathological events that lead to neurodegeneration. Following our previous studies related with the development of multitarget mitochondriotropic antioxidants, this study aims to evaluate whether the π-system extension on the chemical scaffolds of AntiOXCIN2 and AntiOXCIN3 affects their bioactivity and safety profiles. After the synthesis of four triphenylphosphonium (TPP+) conjugates (compounds 2-5), we evaluated their antioxidant properties and their effect on neurotransmitter-metabolizing enzymes. All compounds were potent equine butyrylcholinesterase (eqBChE) and moderate electric eel acetylcholinesterase (eeAChE) inhibitors, with catechols 4 and 5 presenting lower IC50 values than AntiOXCIN2 and AntiOXCIN3, respectively. However, differences in the inhibition potency and selectivity of compounds 2-5 towards non-human and human cholinesterases (ChEs) were observed. Co-crystallization studies with compounds 2-5 in complex with human ChEs (hChEs) showed that these compounds exhibit different binging modes to hAChE and hBChE. Unlike AntiOXCINs, compounds 2-5 displayed moderate human monoamine oxidase (hMAO) inhibitory activity. Moreover, compounds 4 and 5 presented higher ORAC-FL indexes and lower oxidation potential values than the corresponding AntiOXCINs. Catechols 4 and 5 exhibited broader safety windows in differentiated neuroblastoma cells than benzodioxole derivatives 2 and 3. Compound 4 is highlighted as a safe mitochondria-targeted antioxidant with dual ChE/MAO inhibitory activity. Overall, this work is a contribution for the development of dual therapeutic agents addressing both mitochondrial oxidative stress and neurotransmitter depletion. | pt |
dc.language.iso | eng | pt |
dc.publisher | MDPI | pt |
dc.relation | UIDB/00081/2020 | pt |
dc.relation | PTDC/MED-QUI/29164/2017 | pt |
dc.relation | POCI-01-0145-FEDER- 29164 | pt |
dc.relation | PTDC/BIA-MOL/28607/2017 | pt |
dc.relation | POCI-01-0145-FEDER-028607 | pt |
dc.relation | Direction Générale de l’Armement (DGA) and Service de Santé des Armées (SSA) of the French Ministry of Armed Forces | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject | neurodegenerative diseases | pt |
dc.subject | piperine | pt |
dc.subject | triphenylphosphonium | pt |
dc.subject | cholinesterases | pt |
dc.subject | monoamine oxidase | pt |
dc.subject | mitochondria-targeted antioxidants | pt |
dc.title | Fine-Tuning the Biological Profile of Multitarget Mitochondriotropic Antioxidants for Neurodegenerative Diseases | pt |
dc.type | article | - |
degois.publication.firstPage | 329 | pt |
degois.publication.issue | 2 | pt |
degois.publication.title | Antioxidants | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.3390/antiox10020329 | pt |
degois.publication.volume | 10 | pt |
dc.date.embargo | 2021-02-23 | * |
uc.date.periodoEmbargo | 0 | pt |
item.fulltext | Com Texto completo | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.languageiso639-1 | en | - |
item.openairetype | article | - |
item.cerifentitytype | Publications | - |
item.grantfulltext | open | - |
crisitem.project.grantno | Chemistry Research Unit of University of Porto | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0001-8981-231X | - |
crisitem.author.orcid | 0000-0002-5201-9948 | - |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
antioxidants-10-00329-v3.pdf | 2.39 MB | Adobe PDF | View/Open |
SCOPUSTM
Citations
10
checked on Oct 14, 2024
WEB OF SCIENCETM
Citations
10
checked on Oct 2, 2024
Page view(s)
88
checked on Oct 15, 2024
Download(s)
58
checked on Oct 15, 2024
Google ScholarTM
Check
Altmetric
Altmetric
This item is licensed under a Creative Commons License