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Modulating Cytotoxicity with Lego-like Chemistry: Upgrading Mitochondriotropic Antioxidants with Prototypical Cationic Carrier Bricks
dc.contributor.author | Benfeito, Sofia | |
dc.contributor.author | Fernandes, Carlos | |
dc.contributor.author | Chavarria, Daniel | |
dc.contributor.author | Barreiro, Sandra | |
dc.contributor.author | Cagide, Fernando | |
dc.contributor.author | Sequeira, Lisa | |
dc.contributor.author | Teixeira, José | |
dc.contributor.author | Silva, Renata | |
dc.contributor.author | Remião, Fernando | |
dc.contributor.author | Oliveira, Paulo J. | |
dc.contributor.author | Uriarte, Eugenio | |
dc.contributor.author | Borges, Fernanda | |
dc.date.accessioned | 2023-02-20T16:11:15Z | |
dc.date.available | 2023-02-20T16:11:15Z | |
dc.date.issued | 2022 | |
dc.identifier | 10.1021/acs.jmedchem.2c01630 | |
dc.identifier.issn | 00222623 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12728/10202 | |
dc.description.abstract | Although the lipophilic triphenylphosphonium (TPP+) cation is widely used to target antioxidants to mitochondria, TPP+-based derivatives have shown cytotoxicity in several biological in vitro models. We confirmed that Mito.TPP is cytotoxic to both human neuronal (SH-SY5Y) and hepatic (HepG2) cells, decreasing intracellular adenosine triphosphate (ATP) levels, leading to mitochondrial membrane depolarization and reduced mitochondrial mass after 24 h. We surpassed this concern using nitrogen-derived cationic carriers (Mito.PICO, Mito.ISOQ, and Mito.IMIDZ). As opposed to Mito.TPP, these novel compounds were not cytotoxic to SH-SY5Y and HepG2 cells up to 50 μM and after 24 h of incubation. All of the cationic derivatives accumulated inside the mitochondrial matrix and acted as neuroprotective agents against iron(III), hydrogen peroxide, and tert-butyl hydroperoxide insults. The overall data showed that nitrogen-based cationic carriers can modulate the biological performance of mitochondria-directed antioxidants and are an alternative to the TPP cation. | es_ES |
dc.language.iso | en | es_ES |
dc.publisher | American Chemical Society | es_ES |
dc.title | Modulating Cytotoxicity with Lego-like Chemistry: Upgrading Mitochondriotropic Antioxidants with Prototypical Cationic Carrier Bricks | es_ES |
dc.type | Article | es_ES |