BIBLIOS

Tipo
Artigos em Revista

Tipo de Documento
Artigo Completo

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

Participantes na publicação
Catarina Dias (Author)
Ana M. Matos (Author)
CQB
Maria T. Blásquez-Sanchez (Author)
CQB
CQE
Patrícia Calado (Author)
Alice Martins (Author)
Philipp Dätwyler (Author)
Beat Ernst (Author)
M. Paula Macedo (Author)
Nicola Colabufo (Author)
Amélia P. Rauter (Author)
Dep. Química e Bioquímica
CQB

Resumo
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.


Instituição
FACULDADE DE CIÊNCIAS DA UNIVERSIDADE DE LISBOA

Suporte
Pure and Applied Chemistry

Identificadores da Publicação
ISSN - 1365-3075
eISSN - 0033-4545

Editora
Walter de Gruyter GmbH



Identificadores do Documento
DOI - https://doi.org/10.1515/pac-2019-0303
URL - http://dx.doi.org/10.1515/pac-2019-0303

Identificadores de Qualidade
SCIMAGO Q1 (2018) - 1,24 - Chemistry (miscellaneous)

Keywords
medicinal chemistry resveratrol caffeic acid ester biomolecular chemistry bioactive molecules neuroprotection organic synthesis ICS29

Download