Cyclodextrin 3-Functionalized with 8-Hydroxyquinoline as an Antioxidant Inhibitor of Metal-Induced Amyloid Aggregation.

Abstract

Cyclodextrins are used increasingly in pharmacotherapy. Experimental and clinical data suggest that cyclodextrins can be used not only as excipients for marketed drugs, but also as active pharmaceutical ingredients to treat neurological diseases including Niemann-Pick type C disease. Disruption of metal and cholesterol homeostasis, protein misfolding, and aggregation are recognized among the major pathological features in triggering neurodegenerative disorders, and therefore it is becoming more and more evident that the next generation of therapies should have multiple functions to combat the multifactorial nature of diseases. A novel class of compounds obtained by conjugating 8-hydroxyquinoline with cyclodextrin has been proposed to combine antioxidant activity, chelating, antiaggregant, and inclusion ability into one compound designed for metal-associated neurodegenerative diseases. Herein, the synthesis and characterization of the new compound 3A -deoxy-3A -[(8-hydroxyquinolyl)-2-methylamino]-2A (S),3A (R)-β-cyclodextrin is reported. Moreover, the interaction of copper-Aβ and zinc-Aβ amyloid with this class of cyclodextrin conjugates was investigated for the first time. New information about the effects of different modified chelating cyclodextrins may be important for further development of drugs against neurodegenerative disorders.