Antifungal Activity and Possible Mechanism of Action of the Zn (II) Complex With a Schiff Base Against Fluconazole-Resistant Strains of Candida spp. and Cryptococcus neoformans.

The objective of this study was to investigate the antifungal activity of the vanillin-derived Schiff base complexed with zinc (II) (SBZ) against fluconazole-resistant strains of Candida spp. and Cryptococcus neoformans. The broth microdilution assay was performed to determine the minimum inhibitory concentration (MIC). The checkerboard assay was used to evaluate the type of pharmacological interaction of the combination of SBZ with azoles. Flow cytometry and alkaline comet assays were performed to investigate the possible action mechanism of SBZ against Candida albicans and Cryptococcus neoformans. The MIC values of SBZ for Candida spp. ranged from 24 to 74.7 µg/mL and for C. neoformans from 32 to 53.3 µg/mL. The combination of SBZ with both fluconazole and itraconazole resulted in additive and indifferent interactions, respectively. The mechanism of action appears to involve mitochondrial depolarization, increased oxidative stress, and DNA damage, leading to apoptosis. Thus, the SBZ complex shows promising in vitro antifungal activity, and its combination with azoles may contribute to optimizing the efficacy of these drugs, justifying future in vivo investigations.