In vitro activity of juglone (5-hydroxy-1,4-naphthoquinone) against both fluconazole-resistant and susceptible Candida isolates.

BACKGROUND: The rise in antifungal resistance and drug class limitations are causing higher morbidity and mortality rates all over the world. This issue highlights the urgent need for new and improved antifungal drugs with a novel target. AIMS: In order to evaluate whether juglone can be served as an alternative antifungal to cure drug-resistant Candida infections, we studied the in vitro susceptibility of juglone against fluconazole-susceptible and -resistance Candida isolates, alone and in combination. METHODS: Antifungal susceptibility testing was performed according to the CLSI (Clinical and Laboratory Standards Institute) guidelines. RESULTS: Juglone exhibited the highest minimal inhibitory concentration (MIC) values, followed by fluconazole and nystatin. Voriconazole showed significantly better antifungal activity than juglone, fluconazole, and nystatin, with MIC50 and MIC90 of 0.031 and 0.5µg/mL. There were significant differences in MICs of fluconazole (p<0.001) and juglone (p<0.0003) between Candidaalbicans and the rest of the species. Combination of juglone with fluconazole revealed insignificant effects against fluconazole-susceptible and -resistant Candida isolates. Juglone increased the antifungal activity of fluconazole; however, no synergism effects were observed for any combination, and only an insignificant effect was found against all tested Candida species. CONCLUSIONS: Although obtaining new antifungal drugs is a critical point, a completely novel approach should be implemented.

In vitro activity of juglone (5-hydroxy-1, 4-naphthoquinone) against both fluconazole-resistant and susceptible Candida isolates

Background:The rise in antifungal resistance and drug class limitations are causing higher morbidity and mortality rates all over the world. This issue highlights the urgent need for new and improved antifungal drugs with a novel target.Aims:In order to evaluate whether juglone can be served as an alternative antifungal to cure drug-resistant Candida infections, we studied the in vitro susceptibility of juglone against fluconazole-susceptible and -resistance Candida isolates, alone and in combination.Methods:Antifungal susceptibility testing was performed according to the CLSI (Clinical and Laboratory Standards Institute) guidelines.Results:Juglone exhibited the highest minimal inhibitory concentration (MIC) values, followed by fluconazole and nystatin. Voriconazole showed significantly better antifungal activity than juglone, fluconazole, and nystatin, with MIC50 and MIC90 of 0.031 and 0.5μg/mL. There were significant differences in MICs of fluconazole (p<0.001) and juglone (p<0.0003) between Candidaalbicans and the rest of the species. Combination of juglone with fluconazole revealed insignificant effects against fluconazole-susceptible and -resistant Candida isolates. Juglone increased the antifungal activity of fluconazole; however, no synergism effects were observed for any combination, and only an insignificant effect was found against all tested Candida species.Conclusions:Although obtaining new antifungal drugs is a critical point, a completely novel approach should be implemented. (AU)

Antecedentes:El aumento de la resistencia a los antifúngicos y las limitaciones propias de los fármacos son responsables de mayores tasas de morbimortalidad en todo el mundo. Este trabajo destaca la urgente necesidad de nuevos y mejorados fármacos antimicóticos contra una nueva diana.Objetivos:Con el fin de evaluar si la juglona puede servir como un antifúngico alternativo para curar las infecciones por Candida resistentes a los fármacos antifúngicos, hemos estudiado la sensibilidad in vitro a la juglona de aislamientos de Candida sensibles y resistentes al fluconazol, solo y en combinación.Métodos:La prueba de sensibilidad a los antifúngicos se realizó de acuerdo con las guías del Clinical and Laboratory Standards Institute (CLSI).Resultados:La juglona mostró los valores de concentración mínima inhibitoria (CMI) más altos, seguida por el fluconazol y la nistatina. El voriconazol mostró una actividad antifúngica significativamente mejor que la juglona, el fluconazol y la nistatina, con valores de CMI50 y CMI90 de 0,031 y 0,5μg/mL. Hubo diferencias significativas en las CMI del fluconazol (p<0,001) y la juglona (p<0,0003) entre los aislamientos de Candida albicans y aquellos de otras especies. La combinación de juglona con fluconazol reveló efectos insignificantes contra cepas de Candida sensibles y resistentes al fluconazol. La juglona aumentó la actividad antifúngica del fluconazol; sin embargo, no se observaron efectos de sinergia para ninguna combinación y solo se encontró un efecto insignificante contra todas las especies de Candida ensayadas.Conclusiones:Aunque el diseño o el descubrimiento de nuevos fármacos antimicóticos es una tarea crítica, es necesario planificar un abordaje completamente novedoso. (AU)