2-Deoxyglycosylation towards more effective and bioavailable neuroprotective molecules inspired by nature

Detalhes bibliográficos
Autor(a) principal: Dias, Catarina
Data de Publicação: 2019
Outros Autores: Matos, Ana M., Blásquez-Sanchez, Maria T., Calado, Patrícia, Martins, Alice, Dätwyler, Philipp, Ernst, Beat, Macedo, M. Paula, Colabufo, Nicola, Rauter, Amélia P.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/147512
Resumo: Funding: The European Union is gratefully acknowledged for the support of the project “Diagnostic and Drug Discovery Initiative for Alzheimer’s Disease” (D3i4AD), FP7-PEOPLE-2013-IAPP, GA 612347. Fundação para a Ciência e a Tecnologia is also acknowledged for the support of project UID/Multi/0612/2019, Funder Id: http://dx.doi.org/10.13039/501100001871, and for the Ph.D. grant co-sponsored by CIPAN SFRH/ BDE/51998/2012 (CD), Funder Id: http://dx.doi.org/10.13039/501100001871.
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spelling 2-Deoxyglycosylation towards more effective and bioavailable neuroprotective molecules inspired by naturebioactive moleculesbiomolecular chemistrycaffeic acid estercytotoxicitydeoxy glycosideICS-29lipophilicitymedicinal chemistryneuroprotectionorganic synthesisresveratrolChemistry(all)Chemical Engineering(all)Funding: The European Union is gratefully acknowledged for the support of the project “Diagnostic and Drug Discovery Initiative for Alzheimer’s Disease” (D3i4AD), FP7-PEOPLE-2013-IAPP, GA 612347. Fundação para a Ciência e a Tecnologia is also acknowledged for the support of project UID/Multi/0612/2019, Funder Id: http://dx.doi.org/10.13039/501100001871, and for the Ph.D. grant co-sponsored by CIPAN SFRH/ BDE/51998/2012 (CD), Funder Id: http://dx.doi.org/10.13039/501100001871.The neuroprotective role of natural polyphenols is well established but phenolics poor water solubility affects their bioavailability and bioactivity. Aiming to overcome this issue, we were encouraged to investigate the 2-deoxyglycosylation of natural or nature inspired neuroprotective molecules, using glycals as easily accessed glycosyl donors. This robust methodology allowed the generation of a set of new resveratrol and caffeic acid ester glycosides, envisioning more effective and bioavailable compounds. Resveratrol 2-deoxyglycosides were more effective at protecting the neuronal cells from peroxide-induced cytotoxicity than resveratrol itself, while the caffeic acid ester glycoside also showed extraordinary neuroprotection activity. Coefficient partition measurements demonstrated the moderate lipophilicity of resveratrol glycosides, which Log D values are typical of a central nervous system (CNS) drug and ideal for blood-brain barrier (BBB) penetration. Passive permeation assessed by the parallel artificial membrane permeability assay (PAMPA) revealed that 2,6-dideoxy-l-arabino-hexopyranosides were more effective than 2-deoxy-d-arabino-hexopyranosides. The lack of toxicity of the neuroprotective glycosides and their promising physicochemical properties revealed the usefulness of sugar coupling towards the modulation of natural product properties and bioactivity.Centro de Estudos de Doenças Crónicas (CEDOC)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNDias, CatarinaMatos, Ana M.Blásquez-Sanchez, Maria T.Calado, PatríciaMartins, AliceDätwyler, PhilippErnst, BeatMacedo, M. PaulaColabufo, NicolaRauter, Amélia P.2023-01-13T22:10:55Z2019-072019-07-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/147512eng0033-4545PURE: 13920737https://doi.org/10.1515/pac-2019-0303info: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:RCAAP2024-03-11T05:28:40Zoai:run.unl.pt:10362/147512Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:52:58.013989Repositório 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 2-Deoxyglycosylation towards more effective and bioavailable neuroprotective molecules inspired by nature
title 2-Deoxyglycosylation towards more effective and bioavailable neuroprotective molecules inspired by nature
spellingShingle 2-Deoxyglycosylation towards more effective and bioavailable neuroprotective molecules inspired by nature
Dias, Catarina
bioactive molecules
biomolecular chemistry
caffeic acid ester
cytotoxicity
deoxy glycoside
ICS-29
lipophilicity
medicinal chemistry
neuroprotection
organic synthesis
resveratrol
Chemistry(all)
Chemical Engineering(all)
title_short 2-Deoxyglycosylation towards more effective and bioavailable neuroprotective molecules inspired by nature
title_full 2-Deoxyglycosylation towards more effective and bioavailable neuroprotective molecules inspired by nature
title_fullStr 2-Deoxyglycosylation towards more effective and bioavailable neuroprotective molecules inspired by nature
title_full_unstemmed 2-Deoxyglycosylation towards more effective and bioavailable neuroprotective molecules inspired by nature
title_sort 2-Deoxyglycosylation towards more effective and bioavailable neuroprotective molecules inspired by nature
author Dias, Catarina
author_facet Dias, Catarina
Matos, Ana M.
Blásquez-Sanchez, Maria T.
Calado, Patrícia
Martins, Alice
Dätwyler, Philipp
Ernst, Beat
Macedo, M. Paula
Colabufo, Nicola
Rauter, Amélia P.
author_role author
author2 Matos, Ana M.
Blásquez-Sanchez, Maria T.
Calado, Patrícia
Martins, Alice
Dätwyler, Philipp
Ernst, Beat
Macedo, M. Paula
Colabufo, Nicola
Rauter, Amélia P.
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Centro de Estudos de Doenças Crónicas (CEDOC)
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
RUN
dc.contributor.author.fl_str_mv Dias, Catarina
Matos, Ana M.
Blásquez-Sanchez, Maria T.
Calado, Patrícia
Martins, Alice
Dätwyler, Philipp
Ernst, Beat
Macedo, M. Paula
Colabufo, Nicola
Rauter, Amélia P.
dc.subject.por.fl_str_mv bioactive molecules
biomolecular chemistry
caffeic acid ester
cytotoxicity
deoxy glycoside
ICS-29
lipophilicity
medicinal chemistry
neuroprotection
organic synthesis
resveratrol
Chemistry(all)
Chemical Engineering(all)
topic bioactive molecules
biomolecular chemistry
caffeic acid ester
cytotoxicity
deoxy glycoside
ICS-29
lipophilicity
medicinal chemistry
neuroprotection
organic synthesis
resveratrol
Chemistry(all)
Chemical Engineering(all)
description Funding: The European Union is gratefully acknowledged for the support of the project “Diagnostic and Drug Discovery Initiative for Alzheimer’s Disease” (D3i4AD), FP7-PEOPLE-2013-IAPP, GA 612347. Fundação para a Ciência e a Tecnologia is also acknowledged for the support of project UID/Multi/0612/2019, Funder Id: http://dx.doi.org/10.13039/501100001871, and for the Ph.D. grant co-sponsored by CIPAN SFRH/ BDE/51998/2012 (CD), Funder Id: http://dx.doi.org/10.13039/501100001871.
publishDate 2019
dc.date.none.fl_str_mv 2019-07
2019-07-01T00:00:00Z
2023-01-13T22:10:55Z
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/10362/147512
url http://hdl.handle.net/10362/147512
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0033-4545
PURE: 13920737
https://doi.org/10.1515/pac-2019-0303
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.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
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