Alkaloid hyemaline exhibits novel in vitro and in vivo antidermatophytic activity.

The global rise in dermatophytosis prevalence, recurrence, and resistance underscores the urgent need for novel antifungal agents and alternative treatment strategies. This study provides the first report of the antidermatophytic activity of hyemaline, a natural alkaloid isolated from Zanthoxylum fagara, against clinically relevant dermatophytes, including Microsporum canis [minimum inhibitory concentration (MIC): 16-128 µg/mL], Trichophyton mentagrophytes (MIC: 2-128 µg/mL), and Trichophyton rubrum (MIC: 16-64 µg/mL). Mechanistic insights from molecular docking suggest hyemaline acts by inhibiting lanosterol 14-alpha demethylase (CYP51). Toxicity assessments conducted in silico and in vivo using a Drosophila melanogaster survival assay confirmed the compound's favorable safety profile. Additionally, in a D. melanogaster infection model, hyemaline treatment increased the survival of infected flies and achieved efficacy comparable to that of commercial antifungals. These findings establish hyemaline as a promising and safe antidermatophytic agent with a well-defined molecular target, warranting further development.