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. and McEwan, Alastair G. (2014) Antimicrobial effects of copper(II) bis(thiosemicarbazonato) complexes provide new insight into their biochemical mode of action. Metallomics, Advance Article 1-10. doi:10.1039/C3MT00348E

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Author Djoko, Karrera Y.
Paterson, Brett M.
Donnelly, Paul S.
McEwan, Alastair G.
Title Antimicrobial effects of copper(II) bis(thiosemicarbazonato) complexes provide new insight into their biochemical mode of action
Formatted title
Antimicrobial effects of copper(ɪɪ) bis(thiosemicarbazonato) complexes provide new insight into their biochemical mode of action
Journal name Metallomics   Check publisher's open access policy
ISSN 1756-5901
1756-591X
Publication date 2014-01-08
Year available 2014
Sub-type Article (original research)
DOI 10.1039/C3MT00348E
Open Access Status Not Open Access
Volume Advance Article
Start page 1
End page 10
Total pages 10
Place of publication Cambridge, United Kingdom
Publisher Royal Society of Chemistry
Language eng
Formatted abstract
The copper(ɪɪ) 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes First published online 08 Jan 2014

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Sun, 09 Feb 2014, 21:09:08 EST by Karrera Djoko on behalf of School of Chemistry & Molecular Biosciences