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

Abstract

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.

Keywords: 5-Hidroxi-1,4-naftoquinona; 5-Hydroxy-1,4-naphthoquinone; Candida; Fluconazole resistance; Juglona; Juglone; Resistencia al fluconazol; Sensibilidad; Susceptibility.