Ruthenium(II)–arene complexes with chelating quinoline ligands as anti-amyloid agents

Abstract

Recent recognition of the soluble form of the amyloid-beta (Aβ) peptide as a neurotoxic agent in Alzheimer’s disease (AD) has spurred the development of agents to target this species. Because Aβ is known to chelate metal ions in solution, metal-based therapeutics are uniquely suited to exploit this affinity, where coordination to Aβ has been shown to impact the neurotoxicity of the peptide. Ruthenium(II)–arene complexes are unique candidates for evaluation, as one face of the molecule is blocked by the hydrophobic arene ring, while coordination to the Aβ peptide can occur on the other side of the molecule. We have prepared and evaluated two Ru(II)–arene complexes with chelating quinoline-based ligands, Ru1 and Ru2, for their respective anti-amyloid abilities. Although both complexes decreased the aggregation of soluble Aβ, Ru1 displayed promise in disrupting formed aggregates of the peptide. These findings represent an exciting new avenue for therapeutic development in AD, where both sides of the aggregation equilibrium are affected.