Ruthenium(II)–arene complexes with chelating quinoline ligands as anti-amyloid agents
- 1 January 2022
- journal article
- research article
- Published by Canadian Science Publishing in Canadian Journal of Chemistry
- Vol. 100 (1), 18-24
- https://doi.org/10.1139/cjc-2021-0180
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.Keywords
This publication has 66 references indexed in Scilit:
- 8-Hydroxyquinolines: a review of their metal chelating properties and medicinal applicationsDrug Design, Development and Therapy, 2013
- Novel clioquinol and its analogous platinum complexes: importance, role of the halogen substitution and the hydroxyl group of the ligandDalton Transactions, 2013
- Sensing Amyloid-β Aggregation Using Luminescent Dipyridophenazine Ruthenium(II) ComplexesJournal of the American Chemical Society, 2011
- Novel Tacrine−8-Hydroxyquinoline Hybrids as Multifunctional Agents for the Treatment of Alzheimer’s Disease, with Neuroprotective, Cholinergic, Antioxidant, and Copper-Complexing PropertiesJournal of Medicinal Chemistry, 2010
- Reactivity of anticancer metallodrugs with serum proteins: new insights from size exclusion chromatography-ICP-MS and ESI-MSJournal of Analytical Atomic Spectrometry, 2010
- Platinum-based inhibitors of amyloid-β as therapeutic agents for Alzheimer's diseaseProceedings of the National Academy of Sciences of the United States of America, 2008
- pKa Estimation of Ruthenium(II)−Arene PTA Complexes and their Hydrolysis Products via a DFT/Continuum Electrostatics ApproachOrganometallics, 2007
- Zinc Binding to Alzheimer's Aβ(1–16) Peptide Results in Stable Soluble ComplexBiochemical and Biophysical Research Communications, 2001
- Treatment with a Copper-Zinc Chelator Markedly and Rapidly Inhibits β-Amyloid Accumulation in Alzheimer's Disease Transgenic MiceNeuron, 2001
- How to measure and predict the molar absorption coefficient of a proteinProtein Science, 1995