• Journal of Microbiology and Biotechnology
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• v.14 no.4
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• pp.693-697
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• 2004

YH-1715R, (2R,3R)-2-(2,4-difluorophenyl)-3-(3-methoxy-1,2,4-isothiazol-3-yl-thio)-1-( 1H-1,2,4-triazol-l-yl)-2-butanol, a new triazole derivative obtained by the structural modification of fluconazole, was found to exhibit potent anti-Candida activity against a wide variety of Candida albicans (C. albicans) (MIC: 0.4-12.5 mg/l). To investigate the mode of action of YH-1715R, its effect on ergosterol biosynthesis in cell-free extracts and whole cells of C. albicans was examined. The inhibitory activity of YH-1715R was approximately ten-fold higher than that of fluconazole. To determine the primary action mechanism of YH-1715R, its inhibitory activity against lanosterol $14\alpha$-demethylase (14$\alpha$-DM), a major target for azole, was measured using gas-liquid chromatography. YH-1715R and fluconazole were found to inhibit 14a-DM with an $IC_{50}$ of 0.015 $\mu$M and 0.01$8\mu$M, respectively, plus the mode of inhibition of YH-1715R and fluconozole was noncompetitive with a $K_i$ of 0.0533$\mu$M and 0.0975$\mu$M.

• Environmental Mutagens and Carcinogens
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• v.18 no.2
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• pp.93-97
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• 1998

The results of chromosome aberration test in mammalian cells in culture (Chinese hamster lung fibroblast cells) showed no induction of structural and numerical aberrations by antifungal agents of YH1715 series regardless of metabolic activation. While positive control group (mitomycin C and benzo(a)pyrene) showed structural chromosome aberrations of 37% and 23%, respectively. The in vivo induction of micronuclei was measured in polychromatic erythrocytes in bone marrow of male ddY mouse given YH1715R and YH1729R at 1, 0.5, 0.25 g/kg by p.o. once. After 24 hours, animals were sacrificed and evaluated 40 the incidence of micronucleated polychromatic erythrocytes in whole erythrocytes. Although a positive response for induction of micronuclei in animals treated with mitomycin C demonstrated the sensitivity of the test system for detection of a chemical clastogen, YH1715R did not induce micronuclei in bone marrow of ddY male mice but induced cytotoxicity to bone marrow cells at the highest concentration (1 g/kg, p〈0.05), and YH1729R induced micronuclei in bone marrow of ddY male mice dose dependently (p<0.05) but did not induce cytotoxicity to bone marrow cells.