Thati, Bhumika and Noble, Andy and Rowan, Raymond and Creaven, Bernadette S. and Walsh, Maureen and McCann, Malachy and Egan, Denise
Mechanism of action of coumarin and silver(I)- coumarin complexes against the pathogenic yeast Candida albicans.
Toxicology in Vitro.
The anti-fungal activity and mode of action of a range of silver(I)- coumarin complexes was examined. The most potent silver(I)- coumarin complexes, namely 7-hydroxycoumarin-3-carboxylatosilver(I), 6-hydroxycoumarin-3-carboxylatosilver(I) and 4-oxy-3-nitrocoumarinbis(1,10-phenanthroline)silver(I), had MIC80 values of between 69.1 and 4.6 M against the pathogenic yeast Candida albicans. These
compounds also reduced respiration, lowered the ergosterol content of cells and increased the trans-membrane leakage of amino acids. A number of the complexes disrupted cytochrome synthesis in the cell and induced the appearance of morphological features consistent with cell death by apoptosis. These compounds appear to act by disrupting the synthesis of cytochromes which directly aVects the cell's
ability to respire. A reduction in respiration leads to a depletion in ergosterol biosynthesis and a consequent disruption of the integrity of the cell membrane. Disruption of cytochrome biosynthesis may induce the onset of apoptosis which has been shown previously to be triggered
by alteration in the location of cytochrome c. Silver(I)- coumarin complexes demonstrate good anti-fungal activity and manifest a mode of action distinct to that of the conventional azole and polyene drugs thus raising the possibility of their use when resistance to conventional
drug has emerged or in combination with such drugs.
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