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

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Metallomics Vol - 6 Issue - 3

Metallomics Vol - 6 Issue - 2

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

Content Provider	Royal Society of Chemistry (RSC)
Author	Paterson, Brett M. McEwan, Alastair G. Donnelly, Paul S. Djoko, Karrera Y.
Copyright Year	2014
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.
Starting Page	854
Ending Page	863
Page Count	10
File Format	HTM / HTML PDF
ISSN	17565901
Volume Number	6
Issue Number	4
Journal	Metallomics
DOI	10.1039/c3mt00348e
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Antimicrobial Oxygen Cell membrane Treatment as prevention Cu NADH Neisseria Succinic acid Nicotinamide adenine dinucleotide Copper Pathogen Lipophilicity Cytoplasm
Content Type	Text
Resource Type	Article
Subject	Chemistry Medicine Metals and Alloys Biochemistry Biomaterials Biophysics

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