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TitleMechanism of Antifungal Activity by 5-Aminoimidazole-4-Carbohydrazonamide Derivatives against Candida albicans and Candida krusei
Author(s)Cerqueira, Fátima
Maia, Marta
Gabriel, Carla
Medeiros, Rui
Cravo, Sara
Ribeiro, Ana Isabel
Dantas, Daniela
Dias, Alice Maria
Saraiva, Lucília
Raimundo, Liliana
Pinto, Eugénia
KeywordsCandida sp
mechanisms of action
reactive oxygen species
dimorphic transition
metabolic viability
Issue date2021
PublisherMultidisciplinary Digital Publishing Institute
CitationCerqueira, F.; Maia, M.; Gabriel, C.; Medeiros, R.; Cravo, S.; Ribeiro, A.I.; Dantas, D.; Dias, A.M.; Saraiva, L.; Raimundo, L.; Pinto, E. Mechanism of Antifungal Activity by 5-Aminoimidazole-4-Carbohydrazonamide Derivatives against Candida albicans and Candida krusei. Antibiotics 2021, 10, 183.
Abstract(s)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 (<i>Z</i>)-5-amino-<i>N</i>’-aryl-1-methyl-1<i>H</i>-imidazole-4-carbohydrazonamides (2h, 2k, 2l) that had previously demonstrated strong antifungal activity against <i>Candida krusei</i> and <i>C. albicans</i> 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 <i>C. krusei</i> 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 <i>C. krusei</i> versus <i>C. albicans</i> 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 <i>C. albicans</i> virulence mechanism.
Publisher version
AccessOpen access
Appears in Collections:CDQuim - Artigos (Papers)

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