Synthesis and Evaluation of New Cyclodextrin Derivatives as Amyloid-β Aggregation Inhibitors

The presence of extracellular amyloid-beta (A beta) plaques is one of the pathological hallmarks of Alzheimer's disease. Appropriately functionalized compounds can modulate amyloidogenesis. Here, we report a new class of cyclodextrin (CyD) derivatives rationally designed to improve the A beta recognition and to modulate its aggregation. In particular, a dimethylamino aromatic moiety was conjugated to beta CyD or gamma CyD to explore how different structural aspects of these derivatives could influence the recognition and the aggregation of A beta. The conjugation of the A beta recognition moiety to CyDs resulted in a significant suppression of the self-assembly propensity of A beta when the dimethylamino aromatic moiety was attached to the upper rim of beta CyD. The activity of the derivatives toward A beta confirms that the conjugation of CyDs with A beta recognition moieties may be considered a promising approach for designing new molecules that interfere with A beta aggregation.