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

Abstract 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, (Me 4 N) 3 [PW 11 O 40 (SiC 3 H 6 NH 2 ) 2 PtCl 2 ] (abbreviated as Pt II ‐PW 11 ) for inhibiting Aβ 42 aggregation. The mechanism of inhibition on Aβ 42 aggregation by Pt II ‐PW 11 was attributed to the multiple interactions of Pt II ‐PW 11 with Aβ 42 including coordination interaction of Pt 2+ in Pt II ‐PW 11 with amino group in Aβ 42 , electrostatic attraction, hydrogen bonding and van der Waals force. In cell‐based assay, Pt II ‐PW 11 displayed remarkable neuroprotective effect for Aβ 42 aggregation‐induced cytotoxicity, leading to increase of cell viability from 49 % to 67 % at a dosage of 8 μ m . More importantly, the Pt II ‐PW 11 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.