Synergistic effect of hydralazine associated with triazoles on Candida spp. in planktonic cells.

Objective: To evaluate the antifungal activity of hydralazine hydrochloride alone and in synergy with azoles against Candida spp. and the action mechanism. Methods: We used broth microdilution assays to determine the MIC, checkerboard assays to investigate synergism, and flow cytometry and molecular docking tests to ascertain action mechanism. Results: Hydralazine alone had antifungal activity in the range of 16-128 µg/ml and synergistic effect with itraconazole versus 100% of the fungal isolates, while there was synergy with fluconazole against 11.11% of the isolates. There was molecular interaction with the receptors exo-B(1,3)-glucanase and CYP51, causing reduced cell viability and DNA damage. Conclusion: Hydralazine is synergistic with itraconazole and triggers cell death of Candida spp. at low concentrations, demonstrating antifungal potential.

Antifungal activity of ß-lapachone against azole-resistant Candida spp. and its aspects upon biofilm formation.

Aim: The purpose of this study was to assess the antifungal effect of ß-lapachone (ß-lap) on azole-resistant strains of Candida spp. in both planktonic and biofilm form. Materials & methods: The antifungal activity of ß-lap was evaluated by broth microdilution, flow cytometry and the comet assay. The cell viability of the biofilms was assessed using the MTT assay. Results: ß-lap showed antifungal activity against resistant strains of Candida spp. in planktonic form. In addition, ß-lap decreased the viability of mature biofilms and inhibited the formation of biofilms in vitro. Conclusion: ß-lap showed antifungal activity against Candida spp., suggesting that the compound can be utilized as an adjunct agent in the treatment of candidiasis.

Synergistic anticandidal activity of etomidate and azoles against clinical fluconazole-resistant Candida isolates.

Aim: The purpose of this study was to evaluate the effect of etomidate alone and in combination with azoles on resistant strains of Candida spp. in both planktonic cells and biofilms. Materials & methods: The antifungal activity of etomidate was assessed by the broth microdilution test; flow cytometric procedures to measure fungal viability, mitochondrial transmembrane potential, free radical generation and cell death; as well detection of DNA damage using the comet assay. The interaction between etomidate and antifungal drugs (itraconazole and fluconazole) was evaluated by the checkerboard assay. Results: Etomidate showed antifungal activity against resistant strains of Candida spp. in planktonic cells and biofilms. Etomidate also presented synergism with fluconazole and itraconazole in planktonic cells and biofilms. Conclusion: Etomidate showed antifungal activity against Candida spp., indicating that it is a possible therapeutic alternative.