Utilize este identificador para referenciar este registo: https://hdl.handle.net/10316/103770
Título: Cytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative Analysis
Autor: Fernandes, Carlos
Videira, Afonso J. C.
Veloso, Caroline D. 
Benfeito, Sofia
Soares, Pedro
Martins, João D. 
Gonçalves, Beatriz Nunes 
Duarte, José F. S.
Santos, António M. S.
Oliveira, Paulo J. 
Borges, Fernanda
Teixeira, José 
Silva, Filomena S. G. 
Palavras-chave: phenolic-based mitochondriotropic antioxidants; quinone-based mitochondriotropic antioxidants; non-targeted antioxidants
Data: 29-Out-2021
Editora: MDPI
Projeto: CENTRO 2020 of PT2020 through the European Regional Development Fund (ERDF) 
PTDC/MED-QUI/29164/2017 
Marie Skłodowska-Curie 
Título da revista, periódico, livro ou evento: Biomolecules
Volume: 11
Número: 11
Resumo: Mitochondriotropic antioxidants (MC3, MC6.2, MC4 and MC7.2) based on dietary antioxidants and analogs (caffeic, hydrocaffeic, trihydroxyphenylpropanoic and trihydroxycinnamic acids) were developed. In this study, we evaluate and compare the cytotoxicity profile of novel mitochondria-targeted molecules (generally known as MitoCINs) on human HepG2 and differentiated SH-SY5Y cells with the quinone-based mitochondria-targeted antioxidants MitoQ and SkQ1 and with two non-targeted antioxidants, resveratrol and coenzyme Q10 (CoQ10). We further evaluate their effects on mitochondrial membrane potential, cellular oxygen consumption and extracellular acidification rates. Overall, MitoCINs derivatives reduced cell viability at concentrations about six times higher than those observed with MitoQ and SkQ1. A toxicity ranking for both cell lines was produced: MC4 < MC7.2 < MC3 < MC6.2. These results suggest that C-6 carbon linker and the presence of a pyrogallol group result in lower cytotoxicity. MC3 and MC6.2 affected the mitochondrial function more significantly relative to MitoQ, SkQ1, resveratrol and CoQ10, while MC4 and MC7.2 displayed around 100-1000 times less cytotoxicity than SkQ1 and MitoQ. Based on the mitochondrial and cytotoxicity cellular data, MC4 and MC7.2 are proposed as leads that can be optimized to develop safe drug candidates with therapeutic application in mitochondrial oxidative stress-related diseases.
URI: https://hdl.handle.net/10316/103770
ISSN: 2218-273X
DOI: 10.3390/biom11111605
Direitos: openAccess
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