Dermatophyte-Selective Imidazole-Thiosemicarbazides: Potent In Vitro Activity Against Trichophyton and Microsporum with No Anti-Candida Effect

Dermatophytes are highly infectious pathogenic fungi that colonize keratinized tissues like skin, hair, and nails, causing superficial infections such as tinea capitis, onychomycosis, tinea corporis, and tinea pedis in humans and animals. In immunocompromised patients, they may invade deeper tissues and organs, leading to severe or life-threatening conditions if untreated or inadequately managed. While most infections respond to topical antifungals, some require complex treatment and show resistance to standard therapies. Therefore, novel antifungal agents are needed. We investigated the antidermatophytic activity of imidazole-thiosemicarbazides against <i>Microsporum canis</i>, <i>Trichophyton</i> spp., and <i>Chrysosporium</i> spp. using the broth microdilution method, comparing results to ketoconazole and amphotericin B through minimal inhibitory concentration (MIC), half-maximal inhibitory concentration (IC₅₀), and selectivity index (SI). Iodine- and bromine-substituted compounds showed the strongest activity, with MICs of 15.15 (IC₅₀ < 1 μM; SI > 213) and 73.46 μg/mL (IC₅₀ < 1 μM; SI > 846) against <i>T. tonsurans</i>, and 3.87 (IC₅₀ = 7.21 μM; SI > 29.6) and 7.38 μg/mL (IC₅₀ = 11.06 μM; SI = 76.6) against <i>M. canis</i>. In silico analysis revealed interactions with α-keratin and lanosterol-14-α demethylase (the azole target enzyme), suggesting enhanced drug retention and action. These findings support these compounds as promising leads for further antifungal development.