Antifungal Activity of the Ethyl Acetate Fraction of Poincianella pluviosa (DC.) L. P. Queiroz in Combination with Fluconazole Against Candida spp.

Introduction: Candida infections represent a major public health concern and the intrinsic and acquired resistance of Candida species to antifungals underscores the need for new therapeutic approaches. In this context, natural products represent a valuable source of bioactive compounds with potential antifungal activity. Methods: The antifungal activity of the Ethyl Acetate Fraction (EAF) of Poincianella pluviosa (DC.) L. P. Queiroz stem bark was evaluated against planktonic Candida spp. by broth microdilution method. The effect of EAF combined with Fluconazole (FLZ) was assessed using the checkerboard assay. The effects of EAF alone and combined with FLZ on Candida albicans morphology and membrane integrity were investigated by scanning electron microscopy and fluorescence microscopy, respectively. The antibiofilm activity of EAF against developing and mature biofilms, as well as its effects on mammalian cell viability, was assessed using tetrazolium-based assays. Results: To our knowledge, this is the first study to investigate the antifungal activity of P. pluviosa stem bark EAF against planktonic and biofilm-associated Candida cells and its interaction with FLZ. EAF exhibited fungistatic activity against all tested strains, including FLZ-resistant isolates, with Minimum Inhibitory Concentrations (MICs) ranging from 31.2 to 500 µg/mL. EAF also reduced the metabolic activity of developing and mature biofilms. The combination of EAF and FLZ showed synergistic activity against most tested strains, reducing the MICs of both compounds. Microscopic analyses revealed reduced metabolic activity in cells treated with EAF alone or combined with FLZ, without detectable changes in cell morphology or cytoplasmic membrane integrity. EAF showed no cytotoxic effects on mammalian cells at the antifungal concentrations tested. Conclusion: These findings highlight the antifungal potential of the stem bark EAF of P. pluviosa, alone and in combination with FLZ, supporting further investigation of EAF as a potential source of bioactive compounds for developing alternative strategies to control Candida infections.