Metal complexes of 1,10-phenanthroline-5,6-dione alter the susceptibility of the yeast Candida albicans to amphotericin B and miconazole

Growth of the pathogenic yeast Candida albicans in sub-MIC (minimum inhibitory concentration) levels of Cu(ClO4)2 6H2O and [Cu(phendio)3](ClO4)2 4H2O (phendio = 1,10-phenanthroline-5,6-dione) increased the concentration of miconazole and amphotericin B required to achieve the MIC90 whereas pre-growt...

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Bibliographic Details
Published in:Biometals 2004-08, Vol.17 (4), p.415-422
Main Authors: Eshwika, Ahmed, Coyle, Barry, Devereux, Michael, McCann, Malachy, Kavanagh, Kevin
Format: Article
Language:English
Subjects:
Amphotericin B - pharmacology
Biosynthesis
Candida
Candida albicans
Candida albicans - cytology
Candida albicans - drug effects
Candida albicans - growth & development
Candida albicans - metabolism
Cell Respiration - drug effects
Copper
Copper - chemistry
Copper - pharmacology
Elevation
Ergosterol - pharmacology
Metal complexes
Miconazole - pharmacology
Microbial Sensitivity Tests
Oxygen - metabolism
Oxygen consumption
Oxygen Consumption - drug effects
Phenanthrolines - chemistry
Phenanthrolines - pharmacology
Respiration
Silver
Silver - chemistry
Silver - pharmacology
Spectrum Analysis
Synthesis
Tolerances
Yeast
Yeasts
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Summary:Growth of the pathogenic yeast Candida albicans in sub-MIC (minimum inhibitory concentration) levels of Cu(ClO4)2 6H2O and [Cu(phendio)3](ClO4)2 4H2O (phendio = 1,10-phenanthroline-5,6-dione) increased the concentration of miconazole and amphotericin B required to achieve the MIC90 whereas pre-growth in AgClO4 and [Ag(phendio)2]ClO4 resulted in a small decrease in the relevant MIC90 values. The copper complexes reduce the oxygen consumption of C. albicans while the silver complexes increase oxygen consumption. In addition, pre-growth of cells in the copper complexes resulted in a lower ergosterol content while the silver complexes induced an elevation in ergosterol synthesis. The ability of copper and silver complexes to alter the susceptibility of C. albicans to miconazole and amphotericin B may be influenced by their action on respiration, since reduced respiration rates correlate with reduced cellular ergosterol which is the target for amphotericin B. Lower levels of ergosterol have previously been associated with elevated tolerance to this drug. In the case of reduced sensitivity to miconazole, tolerance may be mediated by lower ergosterol synthesis giving rise to fewer toxic side products once biosynthesis is inhibited by miconazole.
ISSN:0966-0844
1572-8773
DOI:10.1023/B:BIOM.0000029438.97990.c6