New 8-hydroxyquinoline derivatives as promising therapeutic approaches targeting neurodegeneration
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://doi.org/10.48797/sl.2023.92 |
Resumo: | Background: Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis are recognized as the most prevalent neurodegenerative diseases (NDs), presenting a huge burden for society. These diseases share common pathophysiological mechanisms, such oxidative stress, dysfunction in iron metabolism, ferroptosis, and protein misfolding [1-4]. Given their powerful metal chelating and antioxidant properties, 8-hydroxyquinoline (8-HQs) derivatives have emerged as attractive therapeutic approaches for the development of innovative therapies for NDs [5]. Objective: To assess, in vitro, the neuroprotective effects of 12 newly synthesized 8-HQs with iron chelation and radical scavenging capacity, using differentiated neuronal SH-SY5Y cells as an in vitro model. Methods: The cytotoxicity of 8-HQs was initially evaluated using the MTT reduction and neutral red uptake assays, 24 hours after exposure, to select non-cytotoxic concentrations. The neuroprotective effects of the 8-HQs against the cytotoxicity induced by iron (III), erastin (a ferroptosis inducer), or by the combination of the two aggressors, were then evaluated. Their capacity to decrease tert-butyl hydroperoxide (t-BHP)-induced cytotoxicity was also investigated, aiming to elucidate the potential of the novel 8-HQs derivatives to counteract oxidative stress. The most promising 8-HQs were also tested for their ability to protect against the neurotoxin 1-methyl-4-phenylpyridinium (MPP+), which is frequently used to mimic Parkinson's disease in in vitro models [6]. Results: Some of the 8-HQs significantly protected SH-SY5Y cells against the cytotoxicity induced by iron (III), erastin, or by the combined effects iron (III) + erastin. Moreover, several 8-HQs also remarkably reduced the cytotoxic effects induced by both t-BHP and MPP+. Conclusions: The 8-HQs showed outstanding neuroprotective properties against the harmful effects induced by distinct chemical aggressors, highlighting their potential to become effective disease-modifying agents for counteracting neurodegeneration. |
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7160 |
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New 8-hydroxyquinoline derivatives as promising therapeutic approaches targeting neurodegenerationPosterBackground: Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis are recognized as the most prevalent neurodegenerative diseases (NDs), presenting a huge burden for society. These diseases share common pathophysiological mechanisms, such oxidative stress, dysfunction in iron metabolism, ferroptosis, and protein misfolding [1-4]. Given their powerful metal chelating and antioxidant properties, 8-hydroxyquinoline (8-HQs) derivatives have emerged as attractive therapeutic approaches for the development of innovative therapies for NDs [5]. Objective: To assess, in vitro, the neuroprotective effects of 12 newly synthesized 8-HQs with iron chelation and radical scavenging capacity, using differentiated neuronal SH-SY5Y cells as an in vitro model. Methods: The cytotoxicity of 8-HQs was initially evaluated using the MTT reduction and neutral red uptake assays, 24 hours after exposure, to select non-cytotoxic concentrations. The neuroprotective effects of the 8-HQs against the cytotoxicity induced by iron (III), erastin (a ferroptosis inducer), or by the combination of the two aggressors, were then evaluated. Their capacity to decrease tert-butyl hydroperoxide (t-BHP)-induced cytotoxicity was also investigated, aiming to elucidate the potential of the novel 8-HQs derivatives to counteract oxidative stress. The most promising 8-HQs were also tested for their ability to protect against the neurotoxin 1-methyl-4-phenylpyridinium (MPP+), which is frequently used to mimic Parkinson's disease in in vitro models [6]. Results: Some of the 8-HQs significantly protected SH-SY5Y cells against the cytotoxicity induced by iron (III), erastin, or by the combined effects iron (III) + erastin. Moreover, several 8-HQs also remarkably reduced the cytotoxic effects induced by both t-BHP and MPP+. Conclusions: The 8-HQs showed outstanding neuroprotective properties against the harmful effects induced by distinct chemical aggressors, highlighting their potential to become effective disease-modifying agents for counteracting neurodegeneration.IUCS-CESPU Publishing2023-04-21info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://doi.org/10.48797/sl.2023.92https://doi.org/10.48797/sl.2023.92Scientific Letters; Vol. 1 No. Sup 1 (2023)2795-5117reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAPenghttps://publicacoes.cespu.pt/index.php/sl/article/view/92https://publicacoes.cespu.pt/index.php/sl/article/view/92/36Copyright (c) 2023 R. Marques-Oliveira , A. R. Alfenim, P. Soares , F. Borges , F. Remião, C. Fernandes, R. Silvainfo:eu-repo/semantics/openAccessMarques-Oliveira , R.Alfenim, A. R.Soares , P.Borges , F.Remião, F.Fernandes, C.Silva , R.2023-04-29T08:46:13Zoai:publicacoes.cespu.pt:article/92Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:50:24.298640Repositório 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 |
New 8-hydroxyquinoline derivatives as promising therapeutic approaches targeting neurodegeneration |
title |
New 8-hydroxyquinoline derivatives as promising therapeutic approaches targeting neurodegeneration |
spellingShingle |
New 8-hydroxyquinoline derivatives as promising therapeutic approaches targeting neurodegeneration Marques-Oliveira , R. Poster |
title_short |
New 8-hydroxyquinoline derivatives as promising therapeutic approaches targeting neurodegeneration |
title_full |
New 8-hydroxyquinoline derivatives as promising therapeutic approaches targeting neurodegeneration |
title_fullStr |
New 8-hydroxyquinoline derivatives as promising therapeutic approaches targeting neurodegeneration |
title_full_unstemmed |
New 8-hydroxyquinoline derivatives as promising therapeutic approaches targeting neurodegeneration |
title_sort |
New 8-hydroxyquinoline derivatives as promising therapeutic approaches targeting neurodegeneration |
author |
Marques-Oliveira , R. |
author_facet |
Marques-Oliveira , R. Alfenim, A. R. Soares , P. Borges , F. Remião, F. Fernandes, C. Silva , R. |
author_role |
author |
author2 |
Alfenim, A. R. Soares , P. Borges , F. Remião, F. Fernandes, C. Silva , R. |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Marques-Oliveira , R. Alfenim, A. R. Soares , P. Borges , F. Remião, F. Fernandes, C. Silva , R. |
dc.subject.por.fl_str_mv |
Poster |
topic |
Poster |
description |
Background: Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis are recognized as the most prevalent neurodegenerative diseases (NDs), presenting a huge burden for society. These diseases share common pathophysiological mechanisms, such oxidative stress, dysfunction in iron metabolism, ferroptosis, and protein misfolding [1-4]. Given their powerful metal chelating and antioxidant properties, 8-hydroxyquinoline (8-HQs) derivatives have emerged as attractive therapeutic approaches for the development of innovative therapies for NDs [5]. Objective: To assess, in vitro, the neuroprotective effects of 12 newly synthesized 8-HQs with iron chelation and radical scavenging capacity, using differentiated neuronal SH-SY5Y cells as an in vitro model. Methods: The cytotoxicity of 8-HQs was initially evaluated using the MTT reduction and neutral red uptake assays, 24 hours after exposure, to select non-cytotoxic concentrations. The neuroprotective effects of the 8-HQs against the cytotoxicity induced by iron (III), erastin (a ferroptosis inducer), or by the combination of the two aggressors, were then evaluated. Their capacity to decrease tert-butyl hydroperoxide (t-BHP)-induced cytotoxicity was also investigated, aiming to elucidate the potential of the novel 8-HQs derivatives to counteract oxidative stress. The most promising 8-HQs were also tested for their ability to protect against the neurotoxin 1-methyl-4-phenylpyridinium (MPP+), which is frequently used to mimic Parkinson's disease in in vitro models [6]. Results: Some of the 8-HQs significantly protected SH-SY5Y cells against the cytotoxicity induced by iron (III), erastin, or by the combined effects iron (III) + erastin. Moreover, several 8-HQs also remarkably reduced the cytotoxic effects induced by both t-BHP and MPP+. Conclusions: The 8-HQs showed outstanding neuroprotective properties against the harmful effects induced by distinct chemical aggressors, highlighting their potential to become effective disease-modifying agents for counteracting neurodegeneration. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-04-21 |
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 |
https://doi.org/10.48797/sl.2023.92 https://doi.org/10.48797/sl.2023.92 |
url |
https://doi.org/10.48797/sl.2023.92 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
https://publicacoes.cespu.pt/index.php/sl/article/view/92 https://publicacoes.cespu.pt/index.php/sl/article/view/92/36 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
IUCS-CESPU Publishing |
publisher.none.fl_str_mv |
IUCS-CESPU Publishing |
dc.source.none.fl_str_mv |
Scientific Letters; Vol. 1 No. Sup 1 (2023) 2795-5117 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 |
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1799131583783895040 |