Two mechanisms of butenafine action in Candida albicans.
The mechanism of action of a new benzylamine antimycotic, butenafine hydrochloride, was studied in Candida albicans by using the thiocarbamate antimycotic tolnaftate as a reference drug. Butenafine completely inhibited the growth of a test strain of C. albicans at 25 micrograms/ml and was cidal at 50 micrograms/ml. Tolnaftate did not show any growth-inhibitory activity up to 100 micrograms/ml. Both butenafine and tolnaftate inhibited squalene epoxidation in C. albicans, with 50% inhibitory concentrations being 0.57 and 0.17 microgram/ml, respectively. Butenafine, but not tolnaftate, induced the release of appreciable amounts of Pi from C. albicans cells at 12.5 micrograms/ml. This effect of butenafine was augmented when the cells were pretreated with tolnaftate. The results suggest that the direct membrane-damaging effect of butenafine may play a major role in its anticandidal activity and that the drug-induced alteration in the cellular sterol composition renders the cell membrane more susceptible to the membrane-damaging effect of this drug.
Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., Kyoto, Japan.
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W
Iwatani
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T
Arika
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Yamaguchi
D000085:Acetates / Q000378:metabolism; D000935:Antifungal Agents / Q000494:pharmacology*; D001596:Benzylamines / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D009281:Naphthalenes / Q000494:pharmacology*; D014047:Tolnaftate / Q000494:pharmacology
D000085:Acetates; D000935:Antifungal Agents; D001596:Benzylamines; D008055:Lipids; D009281:Naphthalenes; D014047:Tolnaftate; C067594:butenafine