Insights into the Discovery of Novel Neuroprotective Agents: A Comparative Study between Sulfanylcinnamic Acid Derivatives and Related Phenolic Analogues
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/107177 https://doi.org/10.3390/molecules24234405 |
Resumo: | 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 (Ep) 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 Ep 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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Insights into the Discovery of Novel Neuroprotective Agents: A Comparative Study between Sulfanylcinnamic Acid Derivatives and Related Phenolic Analoguescinnamic acid4-thioferulic acid derivativesferulic acid derivativesantioxidant activitycytotoxicityneuroprotectionAntioxidantsCell Line, TumorChemical PhenomenaCinnamatesFree Radical ScavengersHumansMolecular StructureNeuroprotective AgentsOxidation-ReductionPhenolsStructure-Activity RelationshipSulfhydryl CompoundsDrug DiscoveryExogenous 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 (Ep) 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 Ep 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).MDPI2019-12-02info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/107177http://hdl.handle.net/10316/107177https://doi.org/10.3390/molecules24234405eng1420-3049Chavarria, DanielFernandes, CarlosAguiar, BrandonSilva, TiagoGarrido, JorgeRemião, FernandoOliveira, Paulo J.Uriarte, EugenioBorges, Fernandainfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-06-13T09:57:46Zoai:estudogeral.uc.pt:10316/107177Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:23:32.272188Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
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 |
spellingShingle |
Insights into the Discovery of Novel Neuroprotective Agents: A Comparative Study between Sulfanylcinnamic Acid Derivatives and Related Phenolic Analogues Chavarria, Daniel cinnamic acid 4-thioferulic acid derivatives ferulic acid derivatives antioxidant activity cytotoxicity neuroprotection Antioxidants Cell Line, Tumor Chemical Phenomena Cinnamates Free Radical Scavengers Humans Molecular Structure Neuroprotective Agents Oxidation-Reduction Phenols Structure-Activity Relationship Sulfhydryl Compounds Drug Discovery |
title_short |
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_sort |
Insights into the Discovery of Novel Neuroprotective Agents: A Comparative Study between Sulfanylcinnamic Acid Derivatives and Related Phenolic Analogues |
author |
Chavarria, Daniel |
author_facet |
Chavarria, Daniel Fernandes, Carlos Aguiar, Brandon Silva, Tiago Garrido, Jorge Remião, Fernando Oliveira, Paulo J. Uriarte, Eugenio Borges, Fernanda |
author_role |
author |
author2 |
Fernandes, Carlos Aguiar, Brandon Silva, Tiago Garrido, Jorge Remião, Fernando Oliveira, Paulo J. Uriarte, Eugenio Borges, Fernanda |
author2_role |
author author author author author author author author |
dc.contributor.author.fl_str_mv |
Chavarria, Daniel Fernandes, Carlos Aguiar, Brandon Silva, Tiago Garrido, Jorge Remião, Fernando Oliveira, Paulo J. Uriarte, Eugenio Borges, Fernanda |
dc.subject.por.fl_str_mv |
cinnamic acid 4-thioferulic acid derivatives ferulic acid derivatives antioxidant activity cytotoxicity neuroprotection Antioxidants Cell Line, Tumor Chemical Phenomena Cinnamates Free Radical Scavengers Humans Molecular Structure Neuroprotective Agents Oxidation-Reduction Phenols Structure-Activity Relationship Sulfhydryl Compounds Drug Discovery |
topic |
cinnamic acid 4-thioferulic acid derivatives ferulic acid derivatives antioxidant activity cytotoxicity neuroprotection Antioxidants Cell Line, Tumor Chemical Phenomena Cinnamates Free Radical Scavengers Humans Molecular Structure Neuroprotective Agents Oxidation-Reduction Phenols Structure-Activity Relationship Sulfhydryl Compounds Drug Discovery |
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 (Ep) 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 Ep 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). |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-12-02 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/107177 http://hdl.handle.net/10316/107177 https://doi.org/10.3390/molecules24234405 |
url |
http://hdl.handle.net/10316/107177 https://doi.org/10.3390/molecules24234405 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1420-3049 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134122216521728 |