Thati, Bhumika and Noble, Andy and Rowan, Raymond and Creaven, Bernadette S. and Walsh, Maureen and McCann, Malachy and Egan, Denise and Kavanagh, Kevin (2007) Mechanism of action of coumarin and silver(I)–coumarin complexes against the pathogenic yeast Candida albicans. Toxicology in Vitro, 21 (5). pp. 801-808. ISSN 0887-2333

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Abstract

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 μM 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 affects 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.

Item Type:	Article
Keywords:	Anti-fungal; Candida albicans; Coumarin; Phenanthroline; Silver(I); Yeast;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	7570
Identification Number:	https://doi.org/10.1016/j.tiv.2007.01.022
Depositing User:	Dr. Kevin Kavanagh
Date Deposited:	24 Oct 2016 16:51
Journal or Publication Title:	Toxicology in Vitro
Publisher:	Elsevier
Refereed:	Yes
Funders:	European Social Fund Operational Programme for Industrial Development
URI:	http://www.sciencedirect.com
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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