In Vitro Activity of Organoselenium Compounds Against Trichophyton spp

Background/Objectives: Dermatophytosis is among the most prevalent fungal infections worldwide, and the emergence of antifungal resistance highlights the need for novel the-rapeutic strategies. Organoselenium compounds have demonstrated promising antifungal activity against several pathogenic fungi, although their activity against dermatophytes remains poorly explored. Here we investigate the in vitro antifungal activity of four organoselenium compounds, ebselen, diphenyl diselenide [(PhSe)₂], p-methoxy-diphenyl diselenide (BMD), and bis-(3-trifluoromethyl phenyl) diselenide (CF₃). Methods: Eighteen clinical isolates belonging to the T. mentagrophytes (n = 10) and T. rubrum (n = 8) species complexes were studied and potential synergism with fluconazole (FCZ) also explored. Antifungal susceptibility testing and drug interaction were performed according to Clinical and Laboratory Standards Institute broth microdilution protocols and checkerboard assay, respectively. Results: Ebselen, (PhSe)₂, and BMD inhibited all Trichophyton spp. isolates with a geometric mean (GM) of minimum inhibitory concentration (MIC) less than or equal to 6 µg/mL. CF₃ inhibited 78% (14/18) of the isolates and had higher MICs (GM ≥ 43.5 µg/mL). Combination assays revealed synergistic interactions between FCZ and the organoselenium compounds, ranging from 45% to 89%, without antagonistic interactions. Moreover, FCZ activity was enhanced in 57-86% of resistant isolates, with BMD showing the most favorable profile in combination with FCZ. Conclusions: These findings demonstrate the promising antifungal potential of organoselenium compounds against the major dermatophytes associated with human infection and support further investigation of these compounds, particularly ebselen, (PhSe)₂, and BMD, as novel antifungal agents, either alone or in combination with conventional antifungal drugs.