Inhibition of Aβ peptide aggregation by ruthenium(II) polypyridyl complexes through copper chelation.

Alzheimer's disease (AD) is known as a complex multifactorial syndrome and both metal chelators and amyloid β peptide (Aβ) inhibitors show promise against AD. Herein, four small hybrid compounds have been designed and synthesized utilizing 8-hydroxyquinoline, pyridine or imidazole as chelators and benzimidazole as the recognition moiety for AD treatment. These conjugates can capture Cu2+ from Aβ and become dimers upon Cu2+ coordination and show high efficiency for both Cu2+ elimination and Aβ assembly inhibition. Besides, these designed complexes can inhibit the production of Aβ-induced reactive oxygen species (ROS), protect mitochondria from damage, and improve the survival rate of neuron cells. Our work provides a new strategy to combine hydrophobic interaction and metal ion chelation to design amyloid inhibitors.