engleski

Stereochemistry of menthol has influence on its antifungal activity

Menthol as a moncyclic alcohol possesses several bioactivities, such as: anaesthetic, antipruritic, decongestant, pesticide and bactericidal. The aim of presented study was to compare in vitro antifungal activity of (-)-menthol or levomenthol, (+)-menthol, and racemic menthol. To elucidate possible influences of stereochemistry of molecule, antifungal susceptibility testing using micro-broth serial dilution assay according to CLSI recommendations against clinical isolates of yeasts was used. On the C. albicans ATCC 10231 as a model, the inhibition of germ-tube formation in bovine serum and cytotoxicity screening using fluorescent dye to determine apoptosis/necrosis in sub-MIC concentrations of menthols were performed. Assessment of the rate of cytotoxic activity between stereoisomers was performed using „ time-kill“ assay. (+)-menthol and racemic menthol exhibited lover MIC values than levomenthol against yeasts tested. Furthermore, MIC values (MIC 363± 74 ug/ml) of racemic menthol was significant lower than (-)- and (+)-menthol (MIC 1.227 mg/ml, and 0.8494 mg/ml, respectively). Racemic menthol was found the most potent fungicide, with 50 % decrease of viable blastospores at low concentration (100 ug/ml). In sub-MIC concentration, levomenthol at 50 ug/ml inhibited germ-tubes of C. albicans, followed by racemic menthol at 300 ug/ml. Cytotoxicity using fluorescent dye showed that 50 ug/ml of (+)-menthol significantly decrease the number of viable blastospores, and in concentration 100 ug/ml apoptosis dominate over necrosis. Differences in cytotoxic activity in time were also found between menthol stereoisomers. Results suggest that stereochemistry of menthol have influence on antifungal activity, with consequently differences in cytotoxic and germ-tube formation as well as on ratio of apoptotic/necrotic cells of C. albicans.

methol; antifungal; stereochemistry

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