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  3. Salpyran: A Cu(II) Selective Chelator with Therapeutic Potential

Salpyran: A Cu(II) Selective Chelator with Therapeutic Potential

  • Inorg Chem. 2021 Oct 18;60(20):15310-15320. doi: 10.1021/acs.inorgchem.1c01912.
Jack Devonport 1,  Nikolett Bodnár 2,  Andrew McGown 1,  Mahmoud Bukar Maina 3 4,  Louise C Serpell 3,  Csilla Kállay 2,  John Spencer 1,  George E Kostakis 1
Affiliations

Affiliations

  • 1 Department of Chemistry, School of Life Sciences, University of Sussex, Brighton BN1 9QJ, United Kingdom.
  • 2 Department of Inorganic and Analytical Chemistry, University of Debrecen, H-4032 Debrecen, Hungary.
  • 3 Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton BN1 9QG, United Kingdom.
  • 4 College of Medical Sciences, Yobe State University, KM 7, Sir Kashim Ibrahim Way, PMB 1144 Damaturu, Yobe State, Nigeria.
PMID: 34609139 DOI: 10.1021/acs.inorgchem.1c01912
Abstract

We report the rational design of a tunable Cu(II) chelating scaffold, 2-(((2-((pyridin-2-ylmethyl)amino)ethyl)amino)methyl)phenol, Salpyran (HL). This tetradentate ligand is predicated to have suitable permeation, has an extremely high affinity for Cu compared to clioquinol (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)L]+ 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 from the binary Cu(II)/H2O2 system, demonstrating its potential use as a therapeutic small molecule metal chelator.

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