Cytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative Analysis
Mitochondriotropic antioxidants (MC<sub>3</sub>, MC<sub>6.2</sub>, MC<sub>4</sub> and MC<sub>7.2</sub>) based on dietary antioxidants and analogs (caffeic, hydrocaffeic, trihydroxyphenylpropanoic and trihydroxycinnamic acids) were developed. In this st...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-10-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/11/11/1605 |
| _version_ | 1797511091677298688 |
|---|---|
| author | Carlos Fernandes Afonso J. C. Videira Caroline D. Veloso Sofia Benfeito Pedro Soares João D. Martins Beatriz Gonçalves José F. S. Duarte António M. S. Santos Paulo J. Oliveira Fernanda Borges José Teixeira Filomena S. G. Silva |
| author_facet | Carlos Fernandes Afonso J. C. Videira Caroline D. Veloso Sofia Benfeito Pedro Soares João D. Martins Beatriz Gonçalves José F. S. Duarte António M. S. Santos Paulo J. Oliveira Fernanda Borges José Teixeira Filomena S. G. Silva |
| author_sort | Carlos Fernandes |
| collection | DOAJ |
| description | Mitochondriotropic antioxidants (MC<sub>3</sub>, MC<sub>6.2</sub>, MC<sub>4</sub> and MC<sub>7.2</sub>) 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 SkQ<sub>1</sub> and with two non-targeted antioxidants, resveratrol and coenzyme Q<sub>10</sub> (CoQ<sub>10</sub>). 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: MC<sub>4</sub> < MC<sub>7.2</sub> < MC<sub>3</sub> < MC<sub>6.2</sub>. These results suggest that C-6 carbon linker and the presence of a pyrogallol group result in lower cytotoxicity. MC<sub>3</sub> and MC<sub>6.2</sub> affected the mitochondrial function more significantly relative to MitoQ, SkQ1, resveratrol and CoQ<sub>10</sub>, while MC<sub>4</sub> and MC<sub>7.2</sub> displayed around 100–1000 times less cytotoxicity than SkQ1 and MitoQ. Based on the mitochondrial and cytotoxicity cellular data, MC<sub>4</sub> and MC<sub>7.2</sub> are proposed as leads that can be optimized to develop safe drug candidates with therapeutic application in mitochondrial oxidative stress-related diseases. |
| first_indexed | 2024-03-10T05:40:31Z |
| format | Article |
| id | doaj.art-a860ae5232fb4fd5a4306babf39f3851 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T05:40:31Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-a860ae5232fb4fd5a4306babf39f38512023-11-22T22:33:38ZengMDPI AGBiomolecules2218-273X2021-10-011111160510.3390/biom11111605Cytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative AnalysisCarlos Fernandes0Afonso J. C. Videira1Caroline D. Veloso2Sofia Benfeito3Pedro Soares4João D. Martins5Beatriz Gonçalves6José F. S. Duarte7António M. S. Santos8Paulo J. Oliveira9Fernanda Borges10José Teixeira11Filomena S. G. Silva12Mitotag, Biocant Park, Parque Tecnológico de Cantanhede, Núcleo 04, Lote 4, 3060-197 Cantanhede, PortugalMitotag, Biocant Park, Parque Tecnológico de Cantanhede, Núcleo 04, Lote 4, 3060-197 Cantanhede, PortugalMitotag, Biocant Park, Parque Tecnológico de Cantanhede, Núcleo 04, Lote 4, 3060-197 Cantanhede, PortugalCIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, PortugalCIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, PortugalMitotag, Biocant Park, Parque Tecnológico de Cantanhede, Núcleo 04, Lote 4, 3060-197 Cantanhede, PortugalMitotag, Biocant Park, Parque Tecnológico de Cantanhede, Núcleo 04, Lote 4, 3060-197 Cantanhede, PortugalMitotag, Biocant Park, Parque Tecnológico de Cantanhede, Núcleo 04, Lote 4, 3060-197 Cantanhede, PortugalMitotag, Biocant Park, Parque Tecnológico de Cantanhede, Núcleo 04, Lote 4, 3060-197 Cantanhede, PortugalCNC—Center for Neuroscience and Cell Biology, CIBB—Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, PortugalCIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, PortugalMitotag, Biocant Park, Parque Tecnológico de Cantanhede, Núcleo 04, Lote 4, 3060-197 Cantanhede, PortugalMitotag, Biocant Park, Parque Tecnológico de Cantanhede, Núcleo 04, Lote 4, 3060-197 Cantanhede, PortugalMitochondriotropic antioxidants (MC<sub>3</sub>, MC<sub>6.2</sub>, MC<sub>4</sub> and MC<sub>7.2</sub>) 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 SkQ<sub>1</sub> and with two non-targeted antioxidants, resveratrol and coenzyme Q<sub>10</sub> (CoQ<sub>10</sub>). 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: MC<sub>4</sub> < MC<sub>7.2</sub> < MC<sub>3</sub> < MC<sub>6.2</sub>. These results suggest that C-6 carbon linker and the presence of a pyrogallol group result in lower cytotoxicity. MC<sub>3</sub> and MC<sub>6.2</sub> affected the mitochondrial function more significantly relative to MitoQ, SkQ1, resveratrol and CoQ<sub>10</sub>, while MC<sub>4</sub> and MC<sub>7.2</sub> displayed around 100–1000 times less cytotoxicity than SkQ1 and MitoQ. Based on the mitochondrial and cytotoxicity cellular data, MC<sub>4</sub> and MC<sub>7.2</sub> are proposed as leads that can be optimized to develop safe drug candidates with therapeutic application in mitochondrial oxidative stress-related diseases.https://www.mdpi.com/2218-273X/11/11/1605phenolic-based mitochondriotropic antioxidantsquinone-based mitochondriotropic antioxidantsnon-targeted antioxidants |
| spellingShingle | Carlos Fernandes Afonso J. C. Videira Caroline D. Veloso Sofia Benfeito Pedro Soares João D. Martins Beatriz Gonçalves José F. S. Duarte António M. S. Santos Paulo J. Oliveira Fernanda Borges José Teixeira Filomena S. G. Silva Cytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative Analysis Biomolecules phenolic-based mitochondriotropic antioxidants quinone-based mitochondriotropic antioxidants non-targeted antioxidants |
| title | Cytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative Analysis |
| title_full | Cytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative Analysis |
| title_fullStr | Cytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative Analysis |
| title_full_unstemmed | Cytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative Analysis |
| title_short | Cytotoxicity and Mitochondrial Effects of Phenolic and Quinone-Based Mitochondria-Targeted and Untargeted Antioxidants on Human Neuronal and Hepatic Cell Lines: A Comparative Analysis |
| title_sort | cytotoxicity and mitochondrial effects of phenolic and quinone based mitochondria targeted and untargeted antioxidants on human neuronal and hepatic cell lines a comparative analysis |
| topic | phenolic-based mitochondriotropic antioxidants quinone-based mitochondriotropic antioxidants non-targeted antioxidants |
| url | https://www.mdpi.com/2218-273X/11/11/1605 |
| work_keys_str_mv | AT carlosfernandes cytotoxicityandmitochondrialeffectsofphenolicandquinonebasedmitochondriatargetedanduntargetedantioxidantsonhumanneuronalandhepaticcelllinesacomparativeanalysis AT afonsojcvideira cytotoxicityandmitochondrialeffectsofphenolicandquinonebasedmitochondriatargetedanduntargetedantioxidantsonhumanneuronalandhepaticcelllinesacomparativeanalysis AT carolinedveloso cytotoxicityandmitochondrialeffectsofphenolicandquinonebasedmitochondriatargetedanduntargetedantioxidantsonhumanneuronalandhepaticcelllinesacomparativeanalysis AT sofiabenfeito cytotoxicityandmitochondrialeffectsofphenolicandquinonebasedmitochondriatargetedanduntargetedantioxidantsonhumanneuronalandhepaticcelllinesacomparativeanalysis AT pedrosoares cytotoxicityandmitochondrialeffectsofphenolicandquinonebasedmitochondriatargetedanduntargetedantioxidantsonhumanneuronalandhepaticcelllinesacomparativeanalysis AT joaodmartins cytotoxicityandmitochondrialeffectsofphenolicandquinonebasedmitochondriatargetedanduntargetedantioxidantsonhumanneuronalandhepaticcelllinesacomparativeanalysis AT beatrizgoncalves cytotoxicityandmitochondrialeffectsofphenolicandquinonebasedmitochondriatargetedanduntargetedantioxidantsonhumanneuronalandhepaticcelllinesacomparativeanalysis AT josefsduarte cytotoxicityandmitochondrialeffectsofphenolicandquinonebasedmitochondriatargetedanduntargetedantioxidantsonhumanneuronalandhepaticcelllinesacomparativeanalysis AT antoniomssantos cytotoxicityandmitochondrialeffectsofphenolicandquinonebasedmitochondriatargetedanduntargetedantioxidantsonhumanneuronalandhepaticcelllinesacomparativeanalysis AT paulojoliveira cytotoxicityandmitochondrialeffectsofphenolicandquinonebasedmitochondriatargetedanduntargetedantioxidantsonhumanneuronalandhepaticcelllinesacomparativeanalysis AT fernandaborges cytotoxicityandmitochondrialeffectsofphenolicandquinonebasedmitochondriatargetedanduntargetedantioxidantsonhumanneuronalandhepaticcelllinesacomparativeanalysis AT joseteixeira cytotoxicityandmitochondrialeffectsofphenolicandquinonebasedmitochondriatargetedanduntargetedantioxidantsonhumanneuronalandhepaticcelllinesacomparativeanalysis AT filomenasgsilva cytotoxicityandmitochondrialeffectsofphenolicandquinonebasedmitochondriatargetedanduntargetedantioxidantsonhumanneuronalandhepaticcelllinesacomparativeanalysis |