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Salpyran: a Cu(II) selective chelator with therapeutic potential

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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 Kostakis
We 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 Chemistry

ISSN

0020-1669

Publisher

American Chemical Society

Issue

20

Volume

60

Page range

15310-15320

Department affiliated with

  • Chemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2021-09-20

First Open Access (FOA) Date

2022-10-06

First Compliant Deposit (FCD) Date

2021-09-20

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