BIBLIOS

Tipo
Artigos em Revista

Tipo de Documento
Artigo Completo

Título
Synthesis and effects of flavonoid structure variation on amyloid-beta aggregation

Participantes na publicação
Ana M. Matos (Author)
CQB
Joana S. Cristóvão (Author)
Dmitry V. Yashunsky (Author)
Nikolay E. Nifantiev (Author)
Ana S. Viana (Author)
Dep. Química e Bioquímica
CQB
Cláudio M. Gomes (Author)
Dep. Química e Bioquímica
BioISI
Amélia P. Rauter (Author)
Dep. Química e Bioquímica
CQB

Resumo
Dietary flavonoids and synthetic derivatives have a well-known potential for biomedical applications. In this perspective, we report herein new methodologies to access chrysin and 5,7-dihydroxychromone, and these structures were combined with those of naturally occurring quercetin, luteolin, (+)-dihydroquercetin and apigenin to assemble a set of polyphenols with structure variations for in vitro testing over the aggregation of Alzheimer’s disease (AD) amyloid peptide Aβ1−42. Using thioflavin-T (ThT) monitored kinetics and subsequent mechanistic analysis by curve fitting, we show that catechol-type flavonoids reduce Aβ1−42 fibril content by 30 % at molar ratios over 10. Without affecting secondary nucleation, these compounds accelerate primary nucleation events responsible for early primary oligomer formation, putatively redirecting the latter into off-pathway aggregates. Atomic force microscopy (AFM) imaging of reaction end-points allowed a comprehensive topographical analysis of amyloid aggregate populations formed in the presence of each compound. Formation of Aβ1−42 small oligomers, regarded as the most toxic amyloid structures, seems to be limited by flavonoids with a C2 phenyl group, while flavonol 3-OH is not a beneficial structural feature. Overall, the diversity of structural variations within flavonoids opens avenues for their development as chemical tools in the treatment of AD by tackling the formation and distribution of neurotoxic oligomers species.


Instituição
FACULDADE DE CIÊNCIAS DA UNIVERSIDADE DE LISBOA

Suporte
Pure and Applied Chemistry

Identificadores da Publicação
ISSN - 1365-3075

Editora
Walter de Gruyter GmbH



Identificadores do Documento
DOI - https://doi.org/10.1515/pac-2017-0201
URL - http://dx.doi.org/10.1515/pac-2017-0201

Identificadores de Qualidade
Web Of Science Q1 (2017) - 5.294 - Chemistry Multidisciplinary SCie

Keywords
ICS-28 atomic force microscopy flavonoids amyloid-β aggregation kinetics chemical synthesis ThT fluorescence assay

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