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


    Coyle, Barry and Kavanagh, Kevin and McCann, Malachy and Devereux, Michael and Geraghty, Majella (2003) Mode of anti-fungal activity of 1,10-phenanthroline and its Cu(II), Mn(II) and Ag(I) complexes. Biometals, 16. pp. 321-329. ISSN 0966-0844

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    Abstract

    The mode of action of the anti-fungal compounds, 1,10-phenanthroline (phen), [Cu(phen)2(mal)] · 2H2O, [Mn(phen)2(mal)] · 2H2O and [Ag2(phen)3(mal)] · 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 μg cm−3 and at a concentration of 10 μg 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.

    Item Type: Article
    Keywords: anti-fungal; Candida; fungicidal; fungistatic; metal complexes; 1,10-phenanthroline;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 7591
    Identification Number: https://doi.org/10.1023/A:1020695923788
    Depositing User: Dr. Kevin Kavanagh
    Date Deposited: 02 Nov 2016 16:46
    Journal or Publication Title: Biometals
    Publisher: Kluwer Academic Publishers
    Refereed: Yes
    Funders: Enterprise Ireland (EI)
    URI:

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