+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Novel method for rapid copper chelation assessment confirmed low affinity of D-penicillamine for copper in comparison with trientine and 8-hydroxyquinolines

Novel method for rapid copper chelation assessment confirmed low affinity of D-penicillamine for copper in comparison with trientine and 8-hydroxyquinolines

Journal of Inorganic Biochemistry 123: 80-87

Copper is an essential trace element involved in many physiological processes. Since disorder of copper homeostasis is observed in various pathologies, copper chelators may represent a promising therapeutic tool. This study was aimed at: 1) formation of an in vitro methodology for screening of copper chelators, and 2) detailed analysis of the interaction of copper with clinically used D-penicillamine (D-PEN), triethylenetetramine (trientine), experimentally tested 8-hydroxyquinolines, and the disodium salt of EDTA as a standard chelator. Methodology based on bathocuproinedisulfonic acid disodium salt (BCS), usable at (patho)physiologically relevant pHs (4.5-7.5), enabled assessment of both cuprous and cupric ions chelation and comparison of the relative affinities of the tested compounds for copper. In the case of potent chelators, the stoichiometry could be estimated too. Clioquinol, chloroxine and EDTA formed very stable complexes with Cu(+)/Cu(2+) at all tested pHs, while copper complexes with trientine were stable only under neutral or slightly acidic conditions. Non-substituted 8-hydroxyquinoline was a less efficient copper chelator, but still unequivocally more potent than D-PEN. Both 8-hydroxyquinoline and D-PEN chelation potencies, similarly to that of trientine, were pH-dependent and decreased with pH. Moreover, only D-PEN was able to reduce cupric ions. Conclusively, BCS assay represents a rapid, simple and precise method for copper chelation measurement. In addition, lower binding affinity of D-PEN compared with 8-hydroxyquinolines and trientine was demonstrated.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 036814830

Download citation: RISBibTeXText

PMID: 23563391

DOI: 10.1016/j.jinorgbio.2013.02.011

Related references

Metal binding in chelation therapy x ray crystal structure of a copper i copper ii complex of d penicillamine. Journal of the Chemical Society Chemical Communications (9): 312-313, 1976

Copper chelation in patients with Wilson's disease. A comparison of penicillamine and triethylene tetramine dihydrochloride. Quarterly Journal of Medicine 42(167): 441-452, 1973

Copper chelation by trientine dihydrochloride inhibits liver RFA-induced inflammatory responses in vivo. Inflammation Research 65(12): 1009-1020, 2016

Evaluation of the efficacy of d-penicillamine and trientine as copper chelators using an in vitro technique involving ovine red blood cells. Onderstepoort Journal of Veterinary Research 59(3): 191-195, 1992

Epr of the copper in dopamine beta mono oxygenase ec rapid reduction by ascorbate the steady state redox level chelation with edta and reactivation of the apo enzyme by added copper. European Journal of Biochemistry 103(1): 5-12, 1980

Electron Paramagnetic Resonance of the Copper in Dopamine β-Monooxygenase : Rapid Reduction by Ascorbate, the Steady-State Redox Level, Chelation with EDTA, and Reactivation of the Apoenzyme by Added Copper. Febs Journal 103(1): 5-11, 1980

Electron paramagnetic resonance of the copper in dopamine beta-monooxygenase. Rapid reduction by ascorbate, the steady-state redox level, chelation with EDTA, and reactivation of the apoenzyme by added copper. European Journal of Biochemistry 103(1): 5-11, 1980

Iatrogenic copper deficiency associated with long-term copper chelation for treatment of copper storage disease in a Bedlington Terrier. Journal of the American Veterinary Medical Association 218(10): 1593-7 1580, 2001

Copper chelation therapy dextro penicillamine in intra hepatic cholestasis of childhood. Gut 20(10): A907, 1979

Circular dichroism and resonance raman spectra of the copper ii copper i complex of d penicillamine the mercaptide stretching mode in blue copper proteins. Biochemical & Biophysical Research Communications 91(4): 1273-1279, 1979

Copper chelation by D-penicillamine generates reactive oxygen species that are cytotoxic to human leukemia and breast cancer cells. Free Radical Biology and Medicine 43(9): 1271-1278, 2007

Novel mitochondria targeted copper(ii) complexes of ferrocenyl terpyridine and anticancer active 8-hydroxyquinolines showing remarkable cytotoxicity, DNA and protein binding affinity. Dalton Transactions 46(2): 396-409, 2017

Mechanistic comparison of human high-affinity copper transporter 1-mediated transport between copper ion and cisplatin. Molecular Pharmacology 76(4): 843-853, 2009

Comparison of the biodistribution of copper d penicillamine and copper salicylate in inflamed and non inflamed rats. Australian & New Zealand Journal of Medicine 15(1 Suppl. 1): 185, 1985

Clinical studies with copper intra uterine devices copper t 200 copper t 300 and copper 7 a comparison of results with inert lippes loop. Journal of the Faculty of Medicine Baghdad 18(1/2): 27-34, 1976