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Salpyran: a Cu(II) selective chelator with therapeutic potential
journal contribution
posted on 2023-06-10, 01:00 authored by Jack Devonport, Nikolett Bodnár, Andrew McGownAndrew McGown, Mahmoud MainaMahmoud Maina, Louise SerpellLouise Serpell, Csilla Kállay, John SpencerJohn Spencer, George KostakisGeorge KostakisWe report the rational design of a tuneable Cu(II) chelating scaffold, 2-(((2-((pyridin-2-ylmethyl)amino)ethyl)amino)methyl)phenol, Salpyran. This tetradentate (3N,1O) ligand is predicated to have suitable permeation, has an extremely high affinity for Cu compared to clioquniol (pCu7.4 = 10.65 vs 5.91) and exhibits excellent selectivity for Cu(II) over Zn(II) in aqueous media. Solid and solution studies corroborate the formation of a stable [Cu(II)(3N,1O)]+ monocationic species at physiological pH values (7.4). Its action as an antioxidant was tested in ascorbate, tau and human prion protein assays which reveal that Salpyran prevents the formation of reactive oxygen species (ROS) from the binary Cu(II)/H2O2 system demonstrating its potential use as a therapeutic small molecule metal chelator (SMMC).
Funding
The suprastructure-function relationship between amyloid assemblies and their toxic and infectious potentials; G2555; BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCIL; BBSRC Ref: BB/S003657/1
History
Publication status
- Published
File Version
- Accepted version
Journal
Inorganic ChemistryISSN
0020-1669Publisher
American Chemical SocietyExternal DOI
Issue
20Volume
60Page range
15310-15320Department affiliated with
- Chemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2021-09-20First Open Access (FOA) Date
2022-10-06First Compliant Deposit (FCD) Date
2021-09-20Usage metrics
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