Mode of anti-fungal activity of 1,10-phenanthroline and its Cu(II), Mn(II) and Ag(I) complexes

The mode of action of the anti-fungal compounds, 1,10-phenanthroline (phen), [Cu(phen)2(mal)] x 2H2O, [Mn(phen)2(mal)] x 2H2O and [Ag2(phen)3(mal)] x 2H2O (malH2 = malonic acid), was examined using the pathogenic yeast Candida albicans. The compounds have minimum inhibitory concentrations (MIC'...

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Bibliographic Details
Published in:Biometals 2003-06, Vol.16 (2), p.321-329
Main Authors: Coyle, Barry, Kavanagh, Kevin, McCann, Malachy, Devereux, Michael, Geraghty, Majella
Format: Article
Language:English
Subjects:
Antifungal Agents - pharmacology
Candida albicans
Candida albicans - drug effects
Candida albicans - metabolism
Cell Respiration - drug effects
Copper
Copper - pharmacology
Ergosterol - metabolism
Manganese - pharmacology
Microbial Sensitivity Tests
Mode of action
Organometallic Compounds - pharmacology
Oxygen consumption
Phenanthrolines - pharmacology
Prescription drugs
Respiratory function
Silver - pharmacology
Yeast
Yeasts
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Summary:The mode of action of the anti-fungal compounds, 1,10-phenanthroline (phen), [Cu(phen)2(mal)] x 2H2O, [Mn(phen)2(mal)] x 2H2O and [Ag2(phen)3(mal)] x 2H2O (malH2 = malonic acid), was examined using the pathogenic yeast Candida albicans. The compounds have minimum inhibitory concentrations (MIC's) in the range 1.25-5.0 microg cm(-3) and at a concentration of 10 microg cm(-3) display some fungicidal activity. Yeast cells exposed to these drugs show a diminished ability to reduce 2,3,5-triphenyltetrazolium chloride (TTC), indicating a reduction in respiratory function. Treating exponential and stationary phase yeast cells with phen and the Cu(II) and Mn(II) complexes causes a dramatic increase in oxygen consumption. All of the drugs promote reductions in the levels of cytochromes b and c in the cells, whilst the Ag(I) complex also lowers the amount of cytochrome aa3. Cells treated with phen and the Cu(II) and Ag(I) species show reduced levels of ergosterol whilst the Mn(II) complex induces an increase in the sterol concentration. The general conclusion is that the drugs damage mitochondrial function and uncouple respiration. That the drugs are not uniformly active suggests their bioactivity has a degree of metal-ion dependency. Phen and metal-phen complexes represent a novel set of highly active anti-fungal agents whose mode of action is significantly different to that of the polyene and azole prescription drugs.
ISSN:0966-0844
1572-8773
DOI:10.1023/a:1020695923788