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- Title
Unusual Cyclodextrin Derivatives as a New Avenue to Modulate Self- and Metal-Induced Aβ Aggregation.
- Authors
Oliveri, Valentina; Bellia, Francesco; Pietropaolo, Adriana; Vecchio, Graziella
- Abstract
Mounting evidence suggests an important role of cyclodextrins in providing protection in neurodegenerative disorders. Metal dyshomeostasis is reported to be a pathogenic factor in neurodegeneration because it could be responsible for damage involving oxidative stress and protein aggregation. As such, metal ions represent an effective target. To improve the metal-binding ability of cyclodextrin, we synthesized three new 8-hydroxyquinoline-cyclodextrin conjugates with difunctionalized cyclodextrins. In particular, the 3-difunctionalized regioisomer represents the first example of cyclodextrin with two pendants at the secondary rim, resulting in a promising compound. The derivatives have significant antioxidant capacity and the powerful activity in inhibiting self-induced amyloid-β aggregation seems to be led by synergistic effects of both cyclodextrin and hydroxyquinoline. Moreover, the derivatives are also able to complex metal ions and to inhibit metal-induced protein aggregation. Therefore, these compounds could have potential as therapeutic agents in diseases related to protein aggregation and metal dyshomeostasis.
- Subjects
CYCLODEXTRIN derivatives; MOLECULAR self-assembly; TREATMENT of neurodegeneration; HYDROXYQUINOLINE; ANTIOXIDANTS; AMYLOID beta-protein; COPPER; GLYCOCONJUGATES
- Publication
Chemistry - A European Journal, 2015, Vol 21, Issue 40, p14047
- ISSN
0947-6539
- Publication type
Article
- DOI
10.1002/chem.201502155