Abstract
Dermatophytes can cause infections of the skin, hair and nails. This study aims to investigate the thiosemicarbazides with nitroimidazole moiety against Trichophyton spp. The activity of fourteen thiosemicarbazide derivatives was evaluated against Trichophyton spp. The minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) showing 50% and 90% reduction in fungal growth after 4-7 days of incubation (MFC(50) and MFC(90)) were used. The 6 and 11 (MICs ≤ 125 µg/mL), followed by the 3, 5 and 7 containing a fluorophenyl group (MIC = 125 µg/mL, MFC = 125-250 µg/mL) exhibited the best activity and specifically T. mentagrophytes, respectively. Fluorine-containing derivatives (5-9) demonstrated 2-4-fold higher activity (MIC = 31.25-1000 µg/mL) against T. rubrum than T. mentagrophytes, than their chlorinated counterparts (2-4) with MIC = 62.5-500 µg/mL. The position of the fluorine atom within the phenyl ring was important, as observed for derivatives with fluorine in the meta position (3, 6), while the para position was associated with enhanced selectivity. A methoxy group in the meta position of the phenyl ring exhibited the strongest, broadest-spectrum activity. Notably, the introduction of the trifluoromethylphenyl moiety (pharmacophore) led to the disappearance of antifungal properties.