Bifunctional Copper\nChelators Capable of Reducing\nAβ Aggregation and Aβ-Induced Oxidative Stress

Five bifunctional\ncopper chelating agents, <b>Alz-(1–5)</b>, designed to\nprevent beta-amyloid (Aβ) aggregation, were synthesized,\nand the leader compound (<b>Alz-5</b>) was chosen. <b>Alz-5</b> acts as a bifunctional chelator that can interact with various Aβ\naggregates and reduce their neurotoxicity. Reactive oxygen species\nmeasurements provided by the Pt-nanoelectrode technique in single\nAβ<sub>42</sub>-affected human neuroblastoma SH-SY5Y cells revealed\nsignificant antioxidant activity of <b>Alz-5</b>. AFM data obtained\non Aβ<sub>42</sub> fibrils clearly indicate the antiaggregating\nproperty of <b>Alz-5</b>. To gain insights into the changes\nin the physiomechanical properties of Aβ<sub>42</sub>-affected\ncells, as well as in order to evaluate the antiaggregating ability\nof <b>Alz-5</b>, Young’s modulus mapping on living SH-SY5Y\ncells affected consequently by Aβ<sub>42</sub> and <b>Alz-5</b> was conducted, and the ability of <b>Alz-5</b> to decrease\ncell rigidity induced by Aβ<sub>42</sub> was indisputably proven.\nLow cell toxicity and antioxidating properties, in conjunction with\nAFM and SICM-based biophysical provided on Aβ<sub>42</sub>-affected\nSH-SY5Y cells, support <b>Alz-</b>5 as a potential inhibitor\nof Aβ aggregation.