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. An organic platinum‐substituted polyoxometalate, (Me4N)3[PW11O40(SiC3H6NH2)2PtCl2] (abbreviated as PtII‐PW11) was designed and prepared. It can effectively inhibit Aβ42 aggregation in vitro, reduce Aβ deposition and rescue memory loss in vivo without noticeable cytotoxicity. PtII‐PW11 demonstrates its potential as therapeutic drug for AD treatment.