Journal : Bioorg Med Chem
Title : Synthesis and evaluation of 1,2,3,4-tetrahydro-1-acridone analogues as potential dual inhibitors for amyloid-beta and tau aggregation.
Year : 2018
Volume : 26
Issue : 16
First Page : 4693
Last Page : 4705
Authors : Lv P, Xia CL, Wang N, Liu ZQ, Huang ZS, Huang SL.
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.