Cyclodextrins 3‐Functionalized with 8‐Hydroxyquinolines: Copper‐Binding Ability and Inhibition of Synuclein Aggregation

Abstract

Neurodegenerative diseases such as Parkinson's and Alzheimer's diseases are multifactorial disorders related to protein aggregation, metal dyshomeostasis, and oxidative stress. To advance understanding in this area and to contribute to therapeutic development, many efforts have been directed at devising suitable agents that can target metal ions associated with relevant biomolecules such as α-synuclein. This paper presents a new cyclodextrin-8-hydroxyquinoline conjugate and discusses the properties of four cyclodextrins 3-functionalized with 8-hydroxyquinoline as copper(II) chelators and inhibitors of copper-induced synuclein aggregation. The encouraging results establish the potential of cyclodextrin-8-hydroxyquinoline conjugates as chelators for the control of copper toxicity.

Structural Isomers of Cyclodextrin‐Bearing IOX1 Compound as Inhibitors of Aβ Aggregation

“…Nevertheless, the structure of IOX1 can be easily functionalized through the carboxylic group and for this reason, a series of derivatives has been synthesized and studied with different applications . The conjugation of HQs with sugars improves their properties as demonstrated by us . In particular, the conjugation of β‐CyD with HQ imparts synergistic effects on the inhibition of self‐induced and metal‐induced Aβ aggregation .…”

“…Herein, we report the synthesis and characterization of 6 A ‐deoxy‐6 A ‐[[(8‐hydroxyquinolyl)‐5‐carboxyl]amino]‐β‐cyclodextrin, a 6‐monofunctionalized CyD‐bearing IOX1 compound (CyD6IOX, Figure ). Moreover, we tested the ability of the new compound and its 3‐monofunctionalized isomer (CyD3IOX, Figure ) to inhibit self‐induced Aβ aggregation in order to understand if the two isomers differently modulate aggregation processes.…”

Synthesis and Study of Multifunctional Cyclodextrin–Deferasirox Hybrids

“…The hydrodynamic diameter of aSyn (mean diameter = 6.4 AE 0.3 nm) confirms the presenceo ft he protein in am onomeric state, in keeping with data reportede lsewhere. [36,37] Moreover, the size distribution of aSyn remains substantially unchanged after 24 hours under these conditions. The presence of Fe 3 + and Cu 2 + promotes aggregate formation.…”

“…Anti‐aggregation assay : αSyn solutions (0.5 mg mL −1 ) were buffered at pH 6.6 and 7.4 (MOPS, 20 m m ). Iron‐ and copper‐mediated aggregation of αSyn was studied using suitable FeCl 3 and Cu(ClO 4 ) 2 solutions in order to have a final concentration of 265 μ m in cuvette as reported elsewhere . CyD derivatives were added in an equimolar amount to the copper ions.…”

“…Iron-and copper-mediated aggregation of aSyn was studied using suitable FeCl 3 and Cu(ClO 4 ) 2 solutions in order to have af inal concentration of 265 mm in cuvette as reported elsewhere. [37] CyD derivatives were added in an equimolar amount to the copper ions. Each DLS mea-surement was run by using automated, optimal measurement times, and laser attenuation settings.…”