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Antimicrobial effects of copper(II) bis(thiosemicarbazonato) complexes provide new insight into their biochemical mode of action

Djoko, Karrera Y.; Paterson, Brett M.; Donnelly, Paul S.; McEwan, Alastair G.

Antimicrobial effects of copper(II) bis(thiosemicarbazonato) complexes provide new insight into their biochemical mode of action Thumbnail


Authors

Brett M. Paterson

Paul S. Donnelly

Alastair G. McEwan



Abstract

The copper(II) complexes of bis-thiosemicarbazones (Cu(btsc)) such as Cu(atsm) and Cu(gtsm) are neutral, lipophilic compounds that show promise as therapeutics for the treatment of certain neurological diseases and cancers. Although the effects of these compounds have been described at the cellular level, there is almost no information about their biochemical mode of action. In this work, we showed that Cu(atsm) and Cu(gtsm) displayed antimicrobial activities against the human obligate pathogen Neisseria gonorrhoeae that were more than 100 times more potent than Cu(NO3)2 salt alone. Treatment with Cu(btsc) also produced phenotypes that were consistent with copper poisoning, but the levels of intracellular copper were undetectable by ICP MS. We observed that Cu(btsc) interacted with proteins in the cell membrane. Systematic measurements of O2 uptake further demonstrated that treatment with both Cu(atsm) and Cu(gtsm) led to dose-dependent inhibition of respiratory electron transfer processes via succinate and NADH dehydrogenases. These dehydrogenases were not inhibited by a non-btsc source of CuII. The results led us to conclude that the biochemical mechanism of Cu(btsc) action is likely more complex than the present, simplistic model of copper release into the cytoplasm.

Citation

Djoko, K. Y., Paterson, B. M., Donnelly, P. S., & McEwan, A. G. (2014). Antimicrobial effects of copper(II) bis(thiosemicarbazonato) complexes provide new insight into their biochemical mode of action. Metallomics, 6(4), 854-863. https://doi.org/10.1039/c3mt00348e

Journal Article Type Article
Acceptance Date Jan 7, 2014
Online Publication Date Jan 8, 2014
Publication Date Apr 1, 2014
Deposit Date Sep 6, 2017
Publicly Available Date Jul 18, 2018
Journal Metallomics
Print ISSN 1756-5901
Electronic ISSN 1756-591X
Publisher Oxford University Press
Peer Reviewed Peer Reviewed
Volume 6
Issue 4
Pages 854-863
DOI https://doi.org/10.1039/c3mt00348e

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