Antifungal canthin-6-one series accumulate in lipid droplets and affect fatty acid metabolism in Saccharomyces cerevisiae.
The mechanism of action of antifungal canthin-6-one series was investigated in Saccharomyces cerevisiae. After a rapid uptake, a preferential accumulation of the drug within lipid droplets was observed. The antifungal action of canthin-6-one was found as reversible. Canthin-6-one did not exhibit affinity for sterols, and membrane ergosterol was not necessary for the antifungal activity since the MICs were similar on an ergosterol-deleted and the wild-type S. cerevisiae clones. Relative amount of unsaturated alkyl chain fatty acids was significantly enhanced suggesting a stimulation of desaturase enzyme systems. No synergistic effect was observed between canthin-6-one and amphotericin B, ketoconazole and caspofungine. Canthin-6-one should now be evaluated in vivo against fungal pathogens.
Lagoutte
D
D
Laboratoire de Pharmacognosie et Chimiothérapie Antiparasitaire, UMR 8076 CNRS, Faculté de Pharmacie, Univ Paris-Sud, 92290 Châtenay-Malabry, France.
Nicolas
V
V
Poupon
E
E
Fournet
A
A
Hocquemiller
R
R
Libong
D
D
Chaminade
P
P
Loiseau
P M
PM
D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology*; D002243:Carbolines; D004357:Drug Synergism; D044943:Fatty Acid Desaturases / Q000187:drug effects / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D026121:Indole Alkaloids; D007211:Indoles / Q000302:isolation & purification / Q000494:pharmacology*; D007654:Ketoconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000302:isolation & purification / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae
D000935:Antifungal Agents; D002243:Carbolines; D005227:Fatty Acids; D026121:Indole Alkaloids; D007211:Indoles; D009287:Naphthyridines; C453379:canthin-6-one; D000666:Amphotericin B; D044943:Fatty Acid Desaturases; D007654:Ketoconazole