Fungicidal Activity of the Nitroimidazole–Thiosemicarbazide Derivative 1-[(1-methyl-4-nitroimidazol-2-yl)carbonyl]-4-(3-methylophenyl)thiosemicarbazide Against Trichophyton spp. Dermatophytes

Dermatophytosis caused by Trichophyton spp. represents a growing public health concern, exacerbated by the increasing prevalence of difficult-to-treat infections and the emergence of resistance to standard antifungal agents, such as terbinafine. In this study, we evaluated the in vitro antifungal activity of a thiosemicarbazide derivative, 1-[(1-methyl-4-nitroimidazol-2-yl)carbonyl]-4-(3-methylphenyl)thiosemicarbazide, against a panel of anthropophilic and zoophilic Trichophyton spp. dermatophytes. Susceptibility testing was performed via the broth microdilution method to determine the minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs). The compound demonstrated antifungal efficacy against all the strains tested, with MIC values ranging from 31.25 to 125 µg/mL. Crucially, low MFC/MIC ratios (≤4) confirmed a fungicidal effect, which was further corroborated by microscopic analysis revealing severe hyphal damage in treated dermatophytes. The derivative exhibited consistent activity against both T. rubrum and T. mentagrophytes, including clinical isolates. To our knowledge, this is one of the first detailed evaluations of a nitroimidazole–thiosemicarbazide hybrid against Trichophyton spp. that combines quantitative MIC/MFC testing with morphological assessment. The tested thiosemicarbazide derivative noticeably decreased the viability of VERO and A375 cells, but even at the highest tested concentration, after 72 h of incubation, the cellular viability remained at 65%. These findings suggest that the investigated compound is a promising candidate for the development of new fungicidal drugs or disinfectants for the effective prophylaxis or management of superficial mycoses in human and veterinary medicine.