Modulating Cytotoxicity with Lego-like Chemistry: Upgrading Mitochondriotropic Antioxidants with Prototypical Cationic Carrier Bricks

• Tipo: Artigo em Revista Científica Internacional
• Data: 2023

Autores

Benfeito, S (Autor) Outra; Fernandes, C (Autor) Outra; Chavarria, D (Autor) Outra; Barreiro, S (Autor) Outra; Cagide, F (Autor) Outra; Sequeira, L (Autor) Outra; Teixeira, J (Autor) Outra; Silva, R (Autor) Outra; Remiao, F (Autor) Outra; Oliveira, PJ (Autor) Outra; Uriarte, E (Autor) Outra; Fernanda Borges (Autor) FCUP

Revista

Título: Journal of Medicinal Chemistry

Vol. 66

Páginas: 1835-1851

ISSN: 0022-2623

Editora: American Chemical Society

Indexação

ISI Web of Knowledge - 0 Citações

Scopus - 1 Citação

Outras Informações

ID Authenticus: P-00Z-WFT

DOI: 10.1021/acs.jmedchem.2c01630

Abstract (EN): 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 intra-cellular 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 mu M 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 17