BioMedical Research Centre, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich.
Med Mycol. 2010 Feb;48(1):155-60. doi: 10.3109/13693780903114934.
In this study we investigated the in vitro antifungal activity of 10 DNA topoisomerase inhibitors on the growth of Candida albicans. The EUCAST broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of the compounds for C. albicans. In addition, the effect of the inhibitors on the growth mode of C. albicans was investigated by light microscopy imaging. Of the 10 DNA topoisomerase inhibitors tested, only the anti-cancer drug aclarubicin displayed antifungal activity with a determinable MIC value of 8.4 microg/ml (10.3 microM). Aclarubicin was also active against clinical isolates of C. albicans with MIC values ranging between 0.8 and 7.3 microg/ml (1-9 microM). Vitality assays showed that the action of aclarubicin was fungistatic. Four other DNA topoisomerase inhibitors, daunorubicin, doxorubicin, idarubicin and beta-lapachone, affected the morphology of C. albicans. The first three inhibitors encouraged the fungus to grow predominantly in the yeast form, whereas beta-lapachone caused hyphal proliferation. The results of this study indicate that some DNA topoisomerase inhibitors effect the growth and morphology of C. albicans suggesting a possible role as antifungal agents in the treatment of C. albicans infections.
在这项研究中，我们调查了 10 种 DNA 拓扑异构酶抑制剂对白色念珠菌生长的体外抗真菌活性。采用欧盟药敏委员会微量肉汤稀释法测定化合物对白色念珠菌的最小抑菌浓度（MIC）。此外，通过光学显微镜成像研究了抑制剂对白色念珠菌生长模式的影响。在测试的 10 种 DNA 拓扑异构酶抑制剂中，只有抗癌药物阿克拉霉素具有抗真菌活性，其 MIC 值可确定为 8.4μg/ml（10.3μM）。阿克拉霉素对白色念珠菌的临床分离株也具有活性，MIC 值在 0.8 至 7.3μg/ml（1-9μM）之间。活力测定表明阿克拉霉素的作用是抑菌的。其他 4 种 DNA 拓扑异构酶抑制剂柔红霉素、多柔比星、伊达比星和β-拉帕醌影响白色念珠菌的形态。前三种抑制剂促使真菌主要以酵母形式生长，而β-拉帕醌则导致菌丝增殖。本研究结果表明，一些 DNA 拓扑异构酶抑制剂影响白色念珠菌的生长和形态，提示它们可能作为抗真菌药物用于治疗白色念珠菌感染。
