氟康唑
克鲁斯假丝酵母
白色念珠菌
白色体
微生物学
生物
肉汤微量稀释
抗真菌药
作用机理
麦角甾醇
活性氧
咪康唑
化学
药理学
生物化学
最小抑制浓度
体外
抗菌剂
抗真菌
作者
Fátima Cerqueira,Marta Marques Maia,Cynira Any Jovilhana da Silva Gabriel,Rui Medeiros,Sara Cravo,Ana Isabel Ribeiro,Daniela Dantas,Alice Dias,Lucı́lia Saraiva,Liliana Raimundo,Eugénia Pinto
出处
期刊:Antibiotics
[MDPI AG]
日期:2021-02-12
卷期号:10 (2): 183-183
被引量:15
标识
DOI:10.3390/antibiotics10020183
摘要
Systemic mycoses are one major cause of morbidity/mortality among immunocompromised/debilitated individuals. Studying the mechanism of action is a strategy to develop safer/potent antifungals, warning resistance emergence. The major goal of this study was to elucidate the mechanism of action of three (Z)-5-amino-N’-aryl-1-methyl-1H-imidazole-4-carbohydrazonamides (2h, 2k, 2l) that had previously demonstrated strong antifungal activity against Candida krusei and C. albicans ATCC strains. Activity was confirmed against clinical isolates, susceptible or resistant to fluconazole by broth microdilution assay. Ergosterol content (HPLC-DAD), mitochondrial dehydrogenase activity (MTT), reactive oxygen species (ROS) generation (flow cytometry), germ tube inhibition and drug interaction were evaluated. None of the compounds inhibited ergosterol synthesis. Ascorbic acid reduced the antifungal effect of compounds and significantly decreased ROS production. The metabolic viability of C. krusei was significantly reduced for values of 2MIC. Compounds 2h and 2k caused a significant increase in ROS production for MIC values while for 2l a significant increase was only observed for concentrations above MIC. ROS production seems to be involved in antifungal activity and the higher activity against C. krusei versus C. albicans may be related to their unequal sensitivity to different ROS. No synergism with fluconazole or amphotericin was observed, but the association of 2h with fluconazole might be valuable due to the significant inhibition of the dimorphic transition, a C. albicans virulence mechanism.
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