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Synthesis and evaluation of 1,2,3,4-tetrahydro-1-acridone analogues as potential dual inhibitors for amyloid-beta and tau aggregation.

Abstract：

:Amyloid-β (Aβ) 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 Aβ and tau aggregation. In vitro studies showed that compounds 25-30 (20 μM) with N-methylation of the quinolone ring effectively inhibited Aβ1-42 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 Aβ1-42 and tau, inhibit Aβ1-42 β-sheets formation, and prevent tau aggregation in living cells.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Lv P,Xia CL,Wang N,Liu ZQ,Huang ZS,Huang SL

doi

10.1016/j.bmc.2018.08.007

subject

Has Abstract

pub_date

2018-09-01 00:00:00

pages

4693-4705

issue

16

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(18)31114-3

journal_volume

26

pub_type

杂志文章

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