Premium
Bis(8‐hydroxyquinoline) Ligands: Exploring their Potential as Selective Copper‐Binding Agents for Alzheimer's Disease
Author(s) -
Oliveri Valentina,
Vecchio Graziella
Publication year - 2021
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.202100079
Subject(s) - chemistry , 8 hydroxyquinoline , reactive oxygen species , metal , chelation , redox , copper , oxidative stress , glutathione , metal ions in aqueous solution , intracellular , combinatorial chemistry , inorganic chemistry , biochemistry , organic chemistry , enzyme
Amyloid‐β (Aβ) aggregation, metal ion dyshomeostasis, and oxidative stress are pathological features of Alzheimer's disease (AD). Aβ and metal ions form metal‐Aβ complex species that influence the aggregation of Aβ and, in particular, redox metal ions such as Cu lead to the production of reactive oxygen species (ROS). To target metal coordination to Aβ and the reactivities of Cu−Aβ, metal chelating agents must extract Cu 2+ from Aβ in AD pathological conditions. Bis(8‐hydroxyquinoline) ligands can extract Cu 2+ from Aβ and therefore inhibit the Cu‐induced Aβ aggregation and the aerobic oxidation of ascorbate. In particular, N‐butyl‐2,2‐imino‐bis(8‐hydroxyquinoline) can selectively target Cu−Aβ reactivities in the presence of Zn 2+ such as in AD brain patients. The ligands can release Cu in intracellular environments in the presence of a large excess of glutathione, contributing to restore Cu homeostasis.