Boosting caffeic acid performance as antioxidant and monoamine oxidase B/catechol-O-methyltransferase inhibitor
Autor(a) principal: | |
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Data de Publicação: | 2022 |
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/10400.22/22276 |
Resumo: | Increased oxidative stress (OS) and depletion of nigrostriatal dopamine (DA) are closely linked to the neurodegeneration observed in Parkinson’s Disease (PD). Caffeic acid (CA)-based antioxidants were developed, and their inhibitory activities towards monoamine oxidases (MAOs) and catechol O-methyltransferases (COMT) were screened. The results showed that the incorporation of an extra double bond maintained or even boosted the antioxidant properties of CA. α-CN derivatives displayed redox potentials (Ep) similar to CA (1) and inhibited hMAO-B with low μM IC50 values. Moreover, catechol amides acted as MB-COMT inhibitors, showing IC50 values within the low μM range. In general, CA derivatives presented safe cytotoxicity profiles at concentrations up to 10 μM. The formation of reactive oxygen species (ROS) induced by CA derivatives may be underlying the cytotoxic effects observed at higher concentrations. Catechol amides 3–6, 8–11 at 10 μM protected cells against oxidative damage. Compounds 3 and 8 were predicted to cross the blood-brain barrier (BBB) by passive diffusion. In summary, we report for the first time BBB-permeant CA-based multitarget lead compounds that may restore DAergic neurotransmission (dual hMAO-B/MB-COMT inhibition) and prevent oxidative damage. The data represents a groundbreaking advancement towards the discovery of the next generation of new drugs for PD. |
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Boosting caffeic acid performance as antioxidant and monoamine oxidase B/catechol-O-methyltransferase inhibitorParkinson’s diseaseCaffeic acidAntioxidantsCatechol-O-MethyltransferaseMonoamine oxidaseNeuroprotectionIncreased oxidative stress (OS) and depletion of nigrostriatal dopamine (DA) are closely linked to the neurodegeneration observed in Parkinson’s Disease (PD). Caffeic acid (CA)-based antioxidants were developed, and their inhibitory activities towards monoamine oxidases (MAOs) and catechol O-methyltransferases (COMT) were screened. The results showed that the incorporation of an extra double bond maintained or even boosted the antioxidant properties of CA. α-CN derivatives displayed redox potentials (Ep) similar to CA (1) and inhibited hMAO-B with low μM IC50 values. Moreover, catechol amides acted as MB-COMT inhibitors, showing IC50 values within the low μM range. In general, CA derivatives presented safe cytotoxicity profiles at concentrations up to 10 μM. The formation of reactive oxygen species (ROS) induced by CA derivatives may be underlying the cytotoxic effects observed at higher concentrations. Catechol amides 3–6, 8–11 at 10 μM protected cells against oxidative damage. Compounds 3 and 8 were predicted to cross the blood-brain barrier (BBB) by passive diffusion. In summary, we report for the first time BBB-permeant CA-based multitarget lead compounds that may restore DAergic neurotransmission (dual hMAO-B/MB-COMT inhibition) and prevent oxidative damage. The data represents a groundbreaking advancement towards the discovery of the next generation of new drugs for PD.This work was funded by FEDER sfunds through the Operational Programme Competitiveness Factors-COMPETE and national funds by FCT – Foundation for Science and Technology under research grants (Grants UIDB/00081/2020 (CIQUP), PTDC/MED-QUI/29164/2017 – POCI-01-0145-FEDER-29164, LA/P/0056/2020 (IMS), UIDB/04539/ 2020, UIDP/04539/2020, OPENSCREEN-NORTE-01-0145-FEDER- 085468. DC thanks FCT, POPH, FEDER/COMPETE for his grant. SB and PS grants are supported by PT-OPENSCREEN-NORTE-01-0145- FEDER-085468 project.ElsevierRepositório Científico do Instituto Politécnico do PortoChavarria, DanielBenfeito, SofiaSoares, PedroLima, CarlaGarrido, JorgeSerrão, PaulaSoares-da-Silva, PatrícioRemião, FernandoOliveira, Paulo J.Borges, Fernanda20222035-12-31T00:00:00Z2022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.22/22276eng10.1016/j.ejmech.2022.114740metadata only accessinfo: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:RCAAP2023-03-13T13:18:55Zoai:recipp.ipp.pt:10400.22/22276Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:42:20.751788Repositório 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 |
Boosting caffeic acid performance as antioxidant and monoamine oxidase B/catechol-O-methyltransferase inhibitor |
title |
Boosting caffeic acid performance as antioxidant and monoamine oxidase B/catechol-O-methyltransferase inhibitor |
spellingShingle |
Boosting caffeic acid performance as antioxidant and monoamine oxidase B/catechol-O-methyltransferase inhibitor Chavarria, Daniel Parkinson’s disease Caffeic acid Antioxidants Catechol-O-Methyltransferase Monoamine oxidase Neuroprotection |
title_short |
Boosting caffeic acid performance as antioxidant and monoamine oxidase B/catechol-O-methyltransferase inhibitor |
title_full |
Boosting caffeic acid performance as antioxidant and monoamine oxidase B/catechol-O-methyltransferase inhibitor |
title_fullStr |
Boosting caffeic acid performance as antioxidant and monoamine oxidase B/catechol-O-methyltransferase inhibitor |
title_full_unstemmed |
Boosting caffeic acid performance as antioxidant and monoamine oxidase B/catechol-O-methyltransferase inhibitor |
title_sort |
Boosting caffeic acid performance as antioxidant and monoamine oxidase B/catechol-O-methyltransferase inhibitor |
author |
Chavarria, Daniel |
author_facet |
Chavarria, Daniel Benfeito, Sofia Soares, Pedro Lima, Carla Garrido, Jorge Serrão, Paula Soares-da-Silva, Patrício Remião, Fernando Oliveira, Paulo J. Borges, Fernanda |
author_role |
author |
author2 |
Benfeito, Sofia Soares, Pedro Lima, Carla Garrido, Jorge Serrão, Paula Soares-da-Silva, Patrício Remião, Fernando Oliveira, Paulo J. Borges, Fernanda |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Politécnico do Porto |
dc.contributor.author.fl_str_mv |
Chavarria, Daniel Benfeito, Sofia Soares, Pedro Lima, Carla Garrido, Jorge Serrão, Paula Soares-da-Silva, Patrício Remião, Fernando Oliveira, Paulo J. Borges, Fernanda |
dc.subject.por.fl_str_mv |
Parkinson’s disease Caffeic acid Antioxidants Catechol-O-Methyltransferase Monoamine oxidase Neuroprotection |
topic |
Parkinson’s disease Caffeic acid Antioxidants Catechol-O-Methyltransferase Monoamine oxidase Neuroprotection |
description |
Increased oxidative stress (OS) and depletion of nigrostriatal dopamine (DA) are closely linked to the neurodegeneration observed in Parkinson’s Disease (PD). Caffeic acid (CA)-based antioxidants were developed, and their inhibitory activities towards monoamine oxidases (MAOs) and catechol O-methyltransferases (COMT) were screened. The results showed that the incorporation of an extra double bond maintained or even boosted the antioxidant properties of CA. α-CN derivatives displayed redox potentials (Ep) similar to CA (1) and inhibited hMAO-B with low μM IC50 values. Moreover, catechol amides acted as MB-COMT inhibitors, showing IC50 values within the low μM range. In general, CA derivatives presented safe cytotoxicity profiles at concentrations up to 10 μM. The formation of reactive oxygen species (ROS) induced by CA derivatives may be underlying the cytotoxic effects observed at higher concentrations. Catechol amides 3–6, 8–11 at 10 μM protected cells against oxidative damage. Compounds 3 and 8 were predicted to cross the blood-brain barrier (BBB) by passive diffusion. In summary, we report for the first time BBB-permeant CA-based multitarget lead compounds that may restore DAergic neurotransmission (dual hMAO-B/MB-COMT inhibition) and prevent oxidative damage. The data represents a groundbreaking advancement towards the discovery of the next generation of new drugs for PD. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022 2022-01-01T00:00:00Z 2035-12-31T00:00:00Z |
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/10400.22/22276 |
url |
http://hdl.handle.net/10400.22/22276 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1016/j.ejmech.2022.114740 |
dc.rights.driver.fl_str_mv |
metadata only access info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
metadata only access |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
dc.source.none.fl_str_mv |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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