Design and Synthesis of Novel Hybrid 8-Hydroxy Quinoline-Indole Derivatives as Inhibitors of Aβ Self-Aggregation and Metal Chelation-Induced Aβ Aggregation.

ABSTRACT: A series of novel hybrid 8-hydroxyquinoline-indole derivatives (7a-7e, 12a-12b and 18a-18h) were synthesized and screened for inhibitory activity against self-induced and metal-ion induced Aβ_1-42 aggregation as potential treatments for Alzheimer's disease (AD). In vitro studies identified the most inhibitory compounds against self-induced Aβ_1-42 aggregation as 18c, 18d and 18f (EC₅₀ = 1.72, 1.48 and 1.08 µM, respectively) compared to the known anti-amyloid drug, clioquinol (1, EC₅₀ = 9.95 µM). The fluorescence of thioflavin T-stained amyloid formed by Aβ_1-42 aggregation in the presence of Cu²⁺ or Zn²⁺ ions was also dramatically decreased by treatment with 18c

SUBMITTER: Bowroju SK 

PROVIDER: S-EPMC7463714 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature