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Publication details

Document type
Journal articles

Document subtype
Full paper

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

Participants in the publication
Ana M. Matos (Author)
CQB - Centro de Química e Bioquímica 
Joana S. Cristóvão (Author)
Dmitry V. Yashunsky (Author)
Nikolay E. Nifantiev (Author)
Ana S. Viana (Author)
Dep. Química e Bioquímica
CQB - Centro de Química e Bioquímica 
Cláudio M. Gomes (Author)
Dep. Química e Bioquímica
BIOISI - Instituto de Biossistemas e Ciências Integrativas
Amélia P. Rauter (Author)
Dep. Química e Bioquímica
CQB - Centro de Química e Bioquímica 

Scope
International

Refereeing
Yes

Summary
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.

Date of Publication
2017-08-28

Institution
FACULDADE DE CIÊNCIAS DA UNIVERSIDADE DE LISBOA

Where published
Pure and Applied Chemistry

Publication Identifiers
ISSN - 1365-3075

Publisher
Walter de Gruyter GmbH

Volume
89
Number
9

Starting page
1305
Last page
1320

Document Identifiers
DOI - https://doi.org/10.1515/pac-2017-0201
URL - http://dx.doi.org/10.1515/pac-2017-0201

Rankings
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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APA
Ana M. Matos, Joana S. Cristóvão, Dmitry V. Yashunsky, Nikolay E. Nifantiev, Ana S. Viana, Cláudio M. Gomes, Amélia P. Rauter, (2017). Synthesis and effects of flavonoid structure variation on amyloid-beta aggregation. Pure and Applied Chemistry, 89, 1305-1320. ISSN 1365-3075. eISSN . http://dx.doi.org/10.1515/pac-2017-0201

IEEE
Ana M. Matos, Joana S. Cristóvão, Dmitry V. Yashunsky, Nikolay E. Nifantiev, Ana S. Viana, Cláudio M. Gomes, Amélia P. Rauter, "Synthesis and effects of flavonoid structure variation on amyloid-beta aggregation" in Pure and Applied Chemistry, vol. 89, pp. 1305-1320, 2017. 10.1515/pac-2017-0201

BIBTEX
@article{36279, author = {Ana M. Matos and Joana S. Cristóvão and Dmitry V. Yashunsky and Nikolay E. Nifantiev and Ana S. Viana and Cláudio M. Gomes and Amélia P. Rauter}, title = {Synthesis and effects of flavonoid structure variation on amyloid-beta aggregation}, journal = {Pure and Applied Chemistry}, year = 2017, pages = {1305-1320}, volume = 89 }