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Insights into the Discovery of Novel Neuroprotective Agents: A Comparative Study between Sulfanylcinnamic Acid Derivatives and Related Phenolic Analogues

Exogenous antioxidants may be beneficial therapeutic tools to tackle the oxidative damage in neurodegenerative diseases by regulation of the redox state that is critical for cell viability and organ function. Inspired by natural plant polyphenols, a series of cinnamic acid-based thiophenolic and phe...

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Autores principales: Chavarria, Daniel, Fernandes, Carlos, Aguiar, Brandon, Silva, Tiago, Garrido, Jorge, Remião, Fernando, Oliveira, Paulo J., Uriarte, Eugenio, Borges, Fernanda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930627/
https://www.ncbi.nlm.nih.gov/pubmed/31810314
http://dx.doi.org/10.3390/molecules24234405
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author Chavarria, Daniel
Fernandes, Carlos
Aguiar, Brandon
Silva, Tiago
Garrido, Jorge
Remião, Fernando
Oliveira, Paulo J.
Uriarte, Eugenio
Borges, Fernanda
author_facet Chavarria, Daniel
Fernandes, Carlos
Aguiar, Brandon
Silva, Tiago
Garrido, Jorge
Remião, Fernando
Oliveira, Paulo J.
Uriarte, Eugenio
Borges, Fernanda
author_sort Chavarria, Daniel
collection PubMed
description Exogenous antioxidants may be beneficial therapeutic tools to tackle the oxidative damage in neurodegenerative diseases by regulation of the redox state that is critical for cell viability and organ function. Inspired by natural plant polyphenols, a series of cinnamic acid-based thiophenolic and phenolic compounds were synthesized and their antioxidant and neuroprotective properties were studied. In general, our results showed that the replacement of the hydroxyl group (OH) by a sulfhydryl group (SH) increased the radical scavenging activity and enhanced the reaction rate with 1,1-diphenyl-2-picrylhydrazyl radical (DPPH((•))) and galvinoxyl radical (GO((•))). These results correlated well with the lower oxidation potential (E(p)) values of thiophenols. However, a lower peroxyl radical (ROO((•))) scavenging activity was observed for thiophenols in oxygen radical absorbance capacity (ORAC-FL) assay. Furthermore, the introduction of 5-methoxy and 5-phenyl groups in the aromatic ring of 4-thioferulic acid (TFA) 2 and ferulic acid (FA) 1 did not significantly improve their antioxidant activity, despite the slight decrease of E(p) observed for compounds 5, 6, and 9. Concerning cinnamic acid amides, the antioxidant profile was similar to the parent compounds. None of the compounds under study presented significant cytotoxic effects in human differentiated neuroblastoma cells. Thiophenolic amide 3 stands out as the most promising thiophenol-based antioxidant, showing cellular neuroprotective effects against oxidative stress inducers (hydrogen peroxide and iron).
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spelling pubmed-69306272019-12-26 Insights into the Discovery of Novel Neuroprotective Agents: A Comparative Study between Sulfanylcinnamic Acid Derivatives and Related Phenolic Analogues Chavarria, Daniel Fernandes, Carlos Aguiar, Brandon Silva, Tiago Garrido, Jorge Remião, Fernando Oliveira, Paulo J. Uriarte, Eugenio Borges, Fernanda Molecules Article Exogenous antioxidants may be beneficial therapeutic tools to tackle the oxidative damage in neurodegenerative diseases by regulation of the redox state that is critical for cell viability and organ function. Inspired by natural plant polyphenols, a series of cinnamic acid-based thiophenolic and phenolic compounds were synthesized and their antioxidant and neuroprotective properties were studied. In general, our results showed that the replacement of the hydroxyl group (OH) by a sulfhydryl group (SH) increased the radical scavenging activity and enhanced the reaction rate with 1,1-diphenyl-2-picrylhydrazyl radical (DPPH((•))) and galvinoxyl radical (GO((•))). These results correlated well with the lower oxidation potential (E(p)) values of thiophenols. However, a lower peroxyl radical (ROO((•))) scavenging activity was observed for thiophenols in oxygen radical absorbance capacity (ORAC-FL) assay. Furthermore, the introduction of 5-methoxy and 5-phenyl groups in the aromatic ring of 4-thioferulic acid (TFA) 2 and ferulic acid (FA) 1 did not significantly improve their antioxidant activity, despite the slight decrease of E(p) observed for compounds 5, 6, and 9. Concerning cinnamic acid amides, the antioxidant profile was similar to the parent compounds. None of the compounds under study presented significant cytotoxic effects in human differentiated neuroblastoma cells. Thiophenolic amide 3 stands out as the most promising thiophenol-based antioxidant, showing cellular neuroprotective effects against oxidative stress inducers (hydrogen peroxide and iron). MDPI 2019-12-02 /pmc/articles/PMC6930627/ /pubmed/31810314 http://dx.doi.org/10.3390/molecules24234405 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chavarria, Daniel
Fernandes, Carlos
Aguiar, Brandon
Silva, Tiago
Garrido, Jorge
Remião, Fernando
Oliveira, Paulo J.
Uriarte, Eugenio
Borges, Fernanda
Insights into the Discovery of Novel Neuroprotective Agents: A Comparative Study between Sulfanylcinnamic Acid Derivatives and Related Phenolic Analogues
title Insights into the Discovery of Novel Neuroprotective Agents: A Comparative Study between Sulfanylcinnamic Acid Derivatives and Related Phenolic Analogues
title_full Insights into the Discovery of Novel Neuroprotective Agents: A Comparative Study between Sulfanylcinnamic Acid Derivatives and Related Phenolic Analogues
title_fullStr Insights into the Discovery of Novel Neuroprotective Agents: A Comparative Study between Sulfanylcinnamic Acid Derivatives and Related Phenolic Analogues
title_full_unstemmed Insights into the Discovery of Novel Neuroprotective Agents: A Comparative Study between Sulfanylcinnamic Acid Derivatives and Related Phenolic Analogues
title_short Insights into the Discovery of Novel Neuroprotective Agents: A Comparative Study between Sulfanylcinnamic Acid Derivatives and Related Phenolic Analogues
title_sort insights into the discovery of novel neuroprotective agents: a comparative study between sulfanylcinnamic acid derivatives and related phenolic analogues
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930627/
https://www.ncbi.nlm.nih.gov/pubmed/31810314
http://dx.doi.org/10.3390/molecules24234405
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