title: Unusual Cyclodextrin Derivatives as a New Avenue to Modulate Self- and Metal-Induced Aβ Aggregation.
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.
authors: Dipartimento di Scienze Chimiche, Università di Catania, Viale A. Doria 6, 95125, Catania (Italy).|Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici, C.I.R.C.M.S.B, Unità di Ricerca di Catania, 95125 Catania (Italy).
authors: Valentina
authors: V
authors: Oliveri
authors: Istituto di Biostrutture e Bioimmagini, CNR, Via P. Gaifami 18, 95126 Catania, Italy.
authors: Francesco
authors: F
authors: Bellia
authors: Dipartimento di Scienze della Salute, Università di Catanzaro, Viale Europa, 88100 Catanzaro, Italy.
authors: Adriana
authors: A
authors: Pietropaolo
authors: Dipartimento di Scienze Chimiche, Università di Catania, Viale A. Doria 6, 95125, Catania (Italy). gr.vecchio@unict.it.
authors: Graziella
authors: G
authors: Vecchio
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002614:Chelating Agents / Q000737:chemistry*; D056831:Coordination Complexes / Q000737:chemistry*; D003505:Cyclodextrins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006912:Hydroxyquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D008670:Metals / Q000009:adverse effects / Q000737:chemistry*; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D066263:Protein Aggregation, Pathological / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D015032:Zinc / Q000009:adverse effects* / Q000737:chemistry*
chemical_list: C000607489:8-hydroxyquinoline-cyclodextrin; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002614:Chelating Agents; D056831:Coordination Complexes; D003505:Cyclodextrins; D006912:Hydroxyquinolines; D008670:Metals; D015032:Zinc
keywords: 8-hydroxyquinoline; antioxidants; copper; cyclodextrins; glycoconjugates; zinc