Bifunctional Copper Chelators Capable of Reducing Aβ Aggregation and Aβ-Induced Oxidative Stress

Five bifunctional copper chelating agents, Alz-(1-5), designed to prevent beta-amyloid (Aβ) aggregation, were synthesized, and the leader compound (Alz-5) was chosen. Alz-5 acts as a bifunctional chelator that can interact with various Aβ aggregates and reduce their neurotoxicity. Reactive oxygen species measurements provided by the Pt-nanoelectrode technique in single Aβ₄₂-affected human neuroblastoma SH-SY5Y cells revealed significant antioxidant activity of Alz-5. AFM data obtained on Aβ₄₂ fibrils clearly indicate the antiaggregating property of Alz-5. To gain insights into the changes in the physiomechanical properties of Aβ₄₂-affected cells, as well as in order to evaluate the antiaggregating ability of Alz-5, Young's modulus mapping on living SH-SY5Y cells affected consequently by Aβ₄₂ and Alz-5 was conducted, and the ability of Alz-5 to decrease cell rigidity induced by Aβ₄₂ was indisputably proven. Low cell toxicity and antioxidating properties, in conjunction with AFM and SICM-based biophysical provided on Aβ₄₂-affected SH-SY5Y cells, support Alz-5 as a potential inhibitor of Aβ aggregation.