Screening And Mechanism Of Action Of Antifungal Agents

In this study, the new triazole derivative HQQ-3 and fluconazole were tested against 41 isolates of fungi representing 10 species in vitro. HQQ-3 was active against all isolates, and the results suggest that HQQ-3 is more potent than fluconazole on a direct-weight basis. For in vivo testing we used a model of murine systemic infection caused by C. albicans and HQQ-3 was the most potent among the drugs tested under the experimental conditions used in the presnt study. The inhibitory effect of HQQ-3 and fluconazole on ergosterol biosynthesis in whole-cell fungi was studied by thin-layer chromatography (TLC) scanning and by gas chromatography-mass spectrometry (GC-MS), The biochemical comparison of in vitro sterol biosynthesis showed that HQQ-3 interferes with ergosterol biosynthesis by blocking lanosterol metabolism, the same as fluconazole. Using transmission electron microscopy, we showed that HQQ-3 treatment leads to cell membrane degradation. This structural manifestation is likely to be secondary effects due to depletion of ergosterol brought about by HQQ-3 treatment. In this study, we also used DNA chip technology to study cellular responses caused by HQQ-3. These result suggest that HQQ-3 is a promising candidate for development for the treatment of mycosis in humans.