In order to determine the antifungal mechanism of terbinafine (TBF), a new allylamine antimycotic, antifungal action of the drug was compared with that of tolciclate (TOL), a thiocarbamate antimycotic which inhibits squalene epoxidation in the pathway of fungal sterol synthesis, using
C. albicans as a test organism. The results are summarized as follows.
1) TBF even at low concentrations (<1μg/m
l) inhibited to some extent the growth of
C. albicans: almost complete inhibition was seen at concentrations of >5μg/m
l, while TOL did not inhibit even high (80μg/m
l) concentration.
2) The decrease of ergosterol content and accumulation of squalene in cells were observed even at low consentrations (<0.3μg/m
l) of TBF; a similar result was obtained for TOL at 80μg/m
l.
3) TBF, at 10μg/m
l or more concentration, accelerated the release of K
+ and inorganic phosphate from
C. albicans cells, although TOL did not at all, indicating that TBF directly damages the cell membranes at high concentrations of the durg.
These results suggest that TBF partially inhibits the growth of
C. albicans by inhibiting ergosterol synthesis at low concentration and, in addition, completely inhibits it by directly damaging the cell membranes at high concentrations.
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