Development of hydroxybenzoic-based platforms as a solution to deliver dietary antioxidants to mitochondria
Abstract Oxidative stress and mitochondrial dysfunction have been associated with metabolic and age-related diseases. Thus, the prevention of mitochondrial oxidative damage is nowadays a recognized pharmacological strategy to delay disease progression. Epidemiological studies suggested an associatio...
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doaj-af502229b67146f7ac2c1bb743cbb0402020-12-08T01:24:18ZengNature Publishing GroupScientific Reports2045-23222017-07-017111810.1038/s41598-017-07272-yDevelopment of hydroxybenzoic-based platforms as a solution to deliver dietary antioxidants to mitochondriaJosé Teixeira0Catarina Oliveira1Ricardo Amorim2Fernando Cagide3Jorge Garrido4José A. Ribeiro5Carlos M. Pereira6António F. Silva7Paula B. Andrade8Paulo J. Oliveira9Fernanda Borges10CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of PortoCIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of PortoCIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of PortoCIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of PortoCIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of PortoCIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of PortoCIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of PortoCIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of PortoREQUIMTE/LAQV-Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy, University of PortoCNC – Center for Neuroscience and Cell Biology, UC-Biotech Building, Biocant Park –University of CoimbraCIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of PortoAbstract Oxidative stress and mitochondrial dysfunction have been associated with metabolic and age-related diseases. Thus, the prevention of mitochondrial oxidative damage is nowadays a recognized pharmacological strategy to delay disease progression. Epidemiological studies suggested an association between the consumption of polyphenol-rich diet and the prevention of different pathologies, including diseases with a mitochondrial etiology. The development of mitochondrial-targeted antioxidants based on dietary antioxidants may decrease mitochondrial oxidative damage. Herein, we report the design and synthesis of two new mitochondriotropic antioxidants based on hydroxybenzoic acids (AntiOxBENs). The results obtained showed that the novel antioxidants are accumulated inside rat liver mitochondria driven by the organelle transmembrane electric potential and prevented lipid peroxidation, exhibiting low toxicity. Some of the observed effects on mitochondrial bioenergetics resulted from an increase of proton leakage through the mitochondrial inner membrane. The new derivatives present a higher lipophilicity than the parent compounds (protocatechuic and gallic acids) and similar antioxidant and iron chelating properties. AntiOxBENs are valid mitochondriotropic antioxidant prototypes, which can be optimized and used in a next future as drug candidates to prevent or slow mitochondrial oxidative stress associated to several pathologies.https://doi.org/10.1038/s41598-017-07272-y |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
José Teixeira Catarina Oliveira Ricardo Amorim Fernando Cagide Jorge Garrido José A. Ribeiro Carlos M. Pereira António F. Silva Paula B. Andrade Paulo J. Oliveira Fernanda Borges |
spellingShingle |
José Teixeira Catarina Oliveira Ricardo Amorim Fernando Cagide Jorge Garrido José A. Ribeiro Carlos M. Pereira António F. Silva Paula B. Andrade Paulo J. Oliveira Fernanda Borges Development of hydroxybenzoic-based platforms as a solution to deliver dietary antioxidants to mitochondria Scientific Reports |
author_facet |
José Teixeira Catarina Oliveira Ricardo Amorim Fernando Cagide Jorge Garrido José A. Ribeiro Carlos M. Pereira António F. Silva Paula B. Andrade Paulo J. Oliveira Fernanda Borges |
author_sort |
José Teixeira |
title |
Development of hydroxybenzoic-based platforms as a solution to deliver dietary antioxidants to mitochondria |
title_short |
Development of hydroxybenzoic-based platforms as a solution to deliver dietary antioxidants to mitochondria |
title_full |
Development of hydroxybenzoic-based platforms as a solution to deliver dietary antioxidants to mitochondria |
title_fullStr |
Development of hydroxybenzoic-based platforms as a solution to deliver dietary antioxidants to mitochondria |
title_full_unstemmed |
Development of hydroxybenzoic-based platforms as a solution to deliver dietary antioxidants to mitochondria |
title_sort |
development of hydroxybenzoic-based platforms as a solution to deliver dietary antioxidants to mitochondria |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-07-01 |
description |
Abstract Oxidative stress and mitochondrial dysfunction have been associated with metabolic and age-related diseases. Thus, the prevention of mitochondrial oxidative damage is nowadays a recognized pharmacological strategy to delay disease progression. Epidemiological studies suggested an association between the consumption of polyphenol-rich diet and the prevention of different pathologies, including diseases with a mitochondrial etiology. The development of mitochondrial-targeted antioxidants based on dietary antioxidants may decrease mitochondrial oxidative damage. Herein, we report the design and synthesis of two new mitochondriotropic antioxidants based on hydroxybenzoic acids (AntiOxBENs). The results obtained showed that the novel antioxidants are accumulated inside rat liver mitochondria driven by the organelle transmembrane electric potential and prevented lipid peroxidation, exhibiting low toxicity. Some of the observed effects on mitochondrial bioenergetics resulted from an increase of proton leakage through the mitochondrial inner membrane. The new derivatives present a higher lipophilicity than the parent compounds (protocatechuic and gallic acids) and similar antioxidant and iron chelating properties. AntiOxBENs are valid mitochondriotropic antioxidant prototypes, which can be optimized and used in a next future as drug candidates to prevent or slow mitochondrial oxidative stress associated to several pathologies. |
url |
https://doi.org/10.1038/s41598-017-07272-y |
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