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

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. 2018 Sep 1;26(16):4693-4705. doi: 10.1016/j.bmc.2018.08.007.
Peng Lv 1,  Chun-Li Xia 2,  Ning Wang 1,  Zhen-Quan Liu 1,  Zhi-Shu Huang 1,  Shi-Liang Huang 3
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.
  • 2 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China; Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, People's Republic of China.
  • 3 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China. Electronic address: lsshsl@mail.sysu.edu.cn.
PMID: 30107970 DOI: 10.1016/j.bmc.2018.08.007
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.

Keywords

1,2,3,4-Tetrahydro-1-acridone analogues; Aggregation inhibitors; Alzheimer’s disease; Amyloid β; Tau protein.

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