Inhibition of Amyloid-ß Aggregation by Cobalt(III) Schiff Base Complexes: A Computational and Experimental Approach.

Coordination complexes have emerged as prominent modulators of amyloid aggregation via their interaction with the N-terminal histidine residues of amyloid-ß (Aß). Herein, we report the synthesis and characterization of a novel cobalt(III) Schiff base complex with methylamine axial ligands, and we present both computational and experimental data demonstrating the reduction of ß-sheet formation by this complex. The computations include molecular dynamics simulations of both monomeric and pentameric Aß, which demonstrate decreased formation of ß-sheet structures, destabilization of preformed ß-sheets, and suppression of aggregation. These results are consistent with a dose dependence in experimental bulk aggregation data using thioflavin T fluorescence, and overall this study demonstrates useful drug activity of the cobalt complex.