Silyl resveratrol derivatives as potential therapeutic agents for neurodegenerative and neurological diseases.

Natural phenolic compounds found in food have demonstrated interesting preventive and therapeutic effects on a large variety of pathologies. Indeed, some of them, such as resveratrol (RES), have been examined in clinical trials. Nevertheless, their success has been scarce mainly due to their low bio...

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Autores: Belmonte-Reche, Efres, Peñalver, Pablo, Caro, Marta, Mateos-Martín, María Luisa, Adán, Norma, Delgado, Mario, González-Rey, Elena, Morales, Juan Carlos
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/358647
Acceso en línea:http://hdl.handle.net/10261/358647
Access Level:acceso abierto
Palabra clave:Resveratrol
Silyl group
Prodrug
Neurodegenerative diseases
Huntington disease
Multiple sclerosis
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spelling Silyl resveratrol derivatives as potential therapeutic agents for neurodegenerative and neurological diseases.Belmonte-Reche, EfresPeñalver, PabloCaro, MartaMateos-Martín, María LuisaAdán, NormaDelgado, MarioGonzález-Rey, ElenaMorales, Juan CarlosResveratrolSilyl groupProdrugNeurodegenerative diseasesHuntington diseaseMultiple sclerosisNatural phenolic compounds found in food have demonstrated interesting preventive and therapeutic effects on a large variety of pathologies. Indeed, some of them, such as resveratrol (RES), have been examined in clinical trials. Nevertheless, their success has been scarce mainly due to their low bioavailability. In this study, we found serendipitously that O-silyl RES derivatives exerted a better neuroprotective activity than resveratrol itself and decided to explore them as potential drugs for neurodegenerative and neurological diseases. We have also designed and prepared a series of O-silyl RES prodrugs to improve their bioavailability. We found that di-triethylsilyl and di-triisopropylsilyl RES derivatives were better in vitro neuroprotective and anti-inflammatory agents than RES. Among these derivatives and their corresponding acyl-, glycosyl- and carbamoyl-prodrugs, 3,5-triethylsilyl-4’-(6″-octanoylglucopyranosyl) resveratrol 26 showed the best profile on toxicity and neuroprotective activity in zebra fish embryo. Compound 26 was also capable of reducing the loss of motor coordination in a 3-nitropropionic acid mice model of Huntington's disease, in a similar way to RES. However, 26 diminished pro-inflammatory cytokine IL-6 to a higher extent than RES and improved the latency to fall in the rotarod test by 10% with respect to RES. Finally, we investigated 26 and RES as potential treatments on an experimental autoimmune encephalomyelitis (EAE) multiple sclerosis mice model. We observed that, in a therapeutic regimen, 26 significantly diminished the progression of EAE severity and reduced the percentage of animals with moderate to severe clinical score, whereas RES showed no improvement.This work was supported by the Junta de Andalucía (FQM-7316) and Spanish Ministerio de Economía y Competitividad (SAF2017-85602-R). NA's work was supported by a Juan de la Cierva Fellowship from the Spanish Ministerio de Economia y Competitividad.Ministerio de Economía y Competitividad (España)Junta de AndalucíaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2024202420212024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/358647reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1016/j.ejmech.2021.113655Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3586472026-05-22T06:33:51Z
dc.title.none.fl_str_mv Silyl resveratrol derivatives as potential therapeutic agents for neurodegenerative and neurological diseases.
title Silyl resveratrol derivatives as potential therapeutic agents for neurodegenerative and neurological diseases.
spellingShingle Silyl resveratrol derivatives as potential therapeutic agents for neurodegenerative and neurological diseases.
Belmonte-Reche, Efres
Resveratrol
Silyl group
Prodrug
Neurodegenerative diseases
Huntington disease
Multiple sclerosis
title_short Silyl resveratrol derivatives as potential therapeutic agents for neurodegenerative and neurological diseases.
title_full Silyl resveratrol derivatives as potential therapeutic agents for neurodegenerative and neurological diseases.
title_fullStr Silyl resveratrol derivatives as potential therapeutic agents for neurodegenerative and neurological diseases.
title_full_unstemmed Silyl resveratrol derivatives as potential therapeutic agents for neurodegenerative and neurological diseases.
title_sort Silyl resveratrol derivatives as potential therapeutic agents for neurodegenerative and neurological diseases.
dc.creator.none.fl_str_mv Belmonte-Reche, Efres
Peñalver, Pablo
Caro, Marta
Mateos-Martín, María Luisa
Adán, Norma
Delgado, Mario
González-Rey, Elena
Morales, Juan Carlos
author Belmonte-Reche, Efres
author_facet Belmonte-Reche, Efres
Peñalver, Pablo
Caro, Marta
Mateos-Martín, María Luisa
Adán, Norma
Delgado, Mario
González-Rey, Elena
Morales, Juan Carlos
author_role author
author2 Peñalver, Pablo
Caro, Marta
Mateos-Martín, María Luisa
Adán, Norma
Delgado, Mario
González-Rey, Elena
Morales, Juan Carlos
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Junta de Andalucía
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Resveratrol
Silyl group
Prodrug
Neurodegenerative diseases
Huntington disease
Multiple sclerosis
topic Resveratrol
Silyl group
Prodrug
Neurodegenerative diseases
Huntington disease
Multiple sclerosis
description Natural phenolic compounds found in food have demonstrated interesting preventive and therapeutic effects on a large variety of pathologies. Indeed, some of them, such as resveratrol (RES), have been examined in clinical trials. Nevertheless, their success has been scarce mainly due to their low bioavailability. In this study, we found serendipitously that O-silyl RES derivatives exerted a better neuroprotective activity than resveratrol itself and decided to explore them as potential drugs for neurodegenerative and neurological diseases. We have also designed and prepared a series of O-silyl RES prodrugs to improve their bioavailability. We found that di-triethylsilyl and di-triisopropylsilyl RES derivatives were better in vitro neuroprotective and anti-inflammatory agents than RES. Among these derivatives and their corresponding acyl-, glycosyl- and carbamoyl-prodrugs, 3,5-triethylsilyl-4’-(6″-octanoylglucopyranosyl) resveratrol 26 showed the best profile on toxicity and neuroprotective activity in zebra fish embryo. Compound 26 was also capable of reducing the loss of motor coordination in a 3-nitropropionic acid mice model of Huntington's disease, in a similar way to RES. However, 26 diminished pro-inflammatory cytokine IL-6 to a higher extent than RES and improved the latency to fall in the rotarod test by 10% with respect to RES. Finally, we investigated 26 and RES as potential treatments on an experimental autoimmune encephalomyelitis (EAE) multiple sclerosis mice model. We observed that, in a therapeutic regimen, 26 significantly diminished the progression of EAE severity and reduced the percentage of animals with moderate to severe clinical score, whereas RES showed no improvement.
publishDate 2021
dc.date.none.fl_str_mv 2021
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/358647
url http://hdl.handle.net/10261/358647
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1016/j.ejmech.2021.113655
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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