Peer-Reviewed Journal Details
Mandatory Fields
Coyle, B;Kavanagh, K;McCann, M;Devereux, M;Geraghty, M
2003
June
BioMetals
Mode of anti-fungal activity of 1,10-phenanthroline and its Cu(II), Mn(II) and Ag(I) complexes
Published
103 ()
Optional Fields
RAY CRYSTAL-STRUCTURES OCTANEDIOIC ACID ODAH(2) CANDIDA-ALBICANS ANTICANDIDA ACTIVITY RESISTANCE PHEN=1,10-PHENANTHROLINE COPPER(II) SUSCEPTIBILITY UPDATE
16
321
329
The mode of action of the anti-fungal compounds, 1,10-phenanthroline (phen), [Cu( phen) (2)( mal)].2H(2)O, [Mn( phen) (2)( mal)].2H(2)O and[ Ag-2( phen)(3)( mal)].2H(2)O (malH(2) = 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 mug cm(-3) and at a concentration of 10 mug 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 aa(3). 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.
DORDRECHT
0966-0844
Grant Details