Synthesis and evaluation of 1,2,3,4-tetrahydro-1-acridone analogues as potential dual inhibitors for amyloid-beta and tau aggregation.
Bioorg Med Chem
; 26(16): 4693-4705, 2018 09 01.
Article
em En
| MEDLINE
| ID: mdl-30107970
ABSTRACT
Amyloid-ß (Aß) and tau protein are two crucial hallmarks in Alzheimer's disease (AD). Their aggregation forms are thought to be toxic to the neurons in the brain. A series of new 1,2,3,4-tetrahydro-1-acridone analogues were designed, synthesized, and evaluated as potential dual inhibitors for Aß and tau aggregation. In vitro studies showed that compounds 25-30 (20⯵M) with N-methylation of the quinolone ring effectively inhibited Aß1-42 aggregation by 84.7%-99.5% and tau aggregation by 71.2%-101.8%. Their structure-activity relationships are discussed. In particular, 30 could permeate the blood-brain barrier, bind to Aß1-42 and tau, inhibit Aß1-42 ß-sheets formation, and prevent tau aggregation in living cells.
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MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Fármacos do Sistema Nervoso Central
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Peptídeos beta-Amiloides
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Proteínas tau
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Acridonas
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article