Direct membrane-damaging effect of sertaconazole on Candida albicans as a mechanism of its fungicidal activity.
The direct action of 7-chloro-3-[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethoxy- methyl]benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592-32-2) on the membrane integrity of C. albicans is studied by quantifying the leakage of intracellular adenosine triphosphate (ATP) into the medium as an index of the changes in membrane permeability and integrity and cell viability of the culture used. Sertaconazole caused a dose-dependent decrease in intracellular ATP after only 10-min exposure and a concomitant significant increase in extracellular ATP. This behaviour is characteristic of antifungals which are fungicidal as a result of a direct membrane damage. Thus sertaconazole, in addition to the mechanism of action responsible for its fungistatic activity (inhibition of ergosterol synthesis), has a second mechanism of action providing a significant fungicidal activity due to direct cell membrane damage.
Agut
J
J
Research Centre, Ferrer Group, Barcelona, Spain.
Palacín
C
C
Salgado
J
J
Casas
E
E
Sacristán
A
A
Ortiz
J A
JA
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D002462:Cell Membrane / Q000187:drug effects*; D002463:Cell Membrane Permeability / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D007654:Ketoconazole / Q000494:pharmacology; D008825:Miconazole / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013876:Thiophenes / Q000494:pharmacology*
D000935:Antifungal Agents; D007093:Imidazoles; D013876:Thiophenes; C061131:sertaconazole; D008825:Miconazole; D000255:Adenosine Triphosphate; D007654:Ketoconazole