Organoplatinum‐Substituted Polyoxometalate Inhibits β‐amyloid Aggregation for Alzheimer's Therapy

Aggregated β‐amyloid (Aβ) is widely considered as a key factor in triggering progressive loss of neuronal function in Alzheimer's disease (AD), so targeting and inhibiting Aβ aggregation has been broadly recognized as an efficient therapeutic strategy for curing AD. Herein, we designed and prepared an organic platinum‐substituted polyoxometalate, (Me4N)3[PW11O40(SiC3H6NH2)2PtCl2] (abbreviated as PtII‐PW11) for inhibiting Aβ42 aggregation. The mechanism of inhibition on Aβ42 aggregation by PtII‐PW11 was attributed to the multiple interactions of PtII‐PW11 with Aβ42 including coordination interaction of Pt2+ in PtII‐PW11 with amino group in Aβ42, electrostatic attraction, hydrogen bonding and van der Waals force. In cell‐based assay, PtII‐PW11 displayed remarkable neuroprotective effect for Aβ42 aggregation‐induced cytotoxicity, leading to increase of cell viability from 49 % to 67 % at a dosage of 8 μm. More importantly, the PtII‐PW11 greatly reduced Aβ deposition and rescued memory loss in APP/PS1 transgenic AD model mice without noticeable cytotoxicity, demonstrating its potential as drugs for AD treatment. Ein organisches platinsubstituiertes Polyoxometallat, (Me4N)3[PW11O40(SiC3H6NH2)2PtCl2] (PtII‐PW11) wurde entwickelt. PtII‐PW11 kann die Aggregation von Aβ42 in vitro hemmen, die Ablagerung von Aβ verringern und Gedächtnisverlust in vivo ohne nennenswerte Zytotoxizität wiederherstellen. PtII‐PW11 zeigt vielversprechendes Potenzial als Therapeutikum für die Behandlung von Alzheimer.