Synergism and Antifungal Potential of the Flavonoid Diosmin Against Clinical Isolates of Candida spp.

Fungal infections caused by Candida spp. cause potentially fatal infections with high morbidity and mortality rates, particularly in immunocompromised individuals. Their resistance to conventional antifungal drugs is closely associated with biofilm formation, which increasingly limits available therapeutic options, making medical practice a major challenge worldwide. In this context, plant derived compounds are an excellent alternative to be investigated. The objective of this study was to evaluate the antifungal potential of the flavonoid diosmin (DIO) and its synergistic capacity with commercial antifungals against clinical isolates of Candida spp. Susceptibility testing by broth microdilution method showed antifungal activity of DIO against all isolates tested, with minimum inhibitory concentration (MIC90) values ​​ranging from 1150 to 2251 µg/mL. Furthermore, we report the ability of DIO to inhibit biofilm and mature biofilm formation, with a greater inhibitory effect on fungal biofilm formation; this effect with DIO was significantly greater in most cases than that shown by amphotericin B (AFB). Intracellular leakage experiments (260/280 nm) showed damage to the cell membrane. This indicates that the antifungal action of DIO could be associated with damage to the cell membrane integrity and consequent death of these pathogens. Synergism experiments with DIO and fluconazole (FLZ) and DIO and AFB revealed a significant synergistic effect against Candida spp. These results highlight the antifungal and synergistic potential of the flavonoid DIO against antifungal resistant Candida spp. Furthermore, these findings serve as a basis for future studies aimed at elucidating DIO's antimicrobial mechanisms of action and contribute to the search for novel compounds from natural sources with antimicrobial potential.