• Thirty-one metabolites identified in Salvadora persica by UPLC HRESIMS. • Eight compounds bound strongly to fungal β−1,3-glucanosyltransferase. • Ethanolic extract showed strong antifungal effect on Mucor circinelloides . • MIC and MFC values (15.62, 31.25 µg/mL) comparable to fluconazole. • Findings support Meswak’s oral use and reveal a new antifungal mechanism. Mucormycosis caused by Mucor circinelloides is a life-threatening fungal infection with limited antifungal treatment options, underscoring the need for new therapeutic leads. This study investigated the antimycotic potential of the ethanolic extract of Salvadora persica (miswak) aerial-parts using an integrated in vitro and in silico approach. Metabolite profiling by UPLC HRESIMS enabled the tentative annotation of thirty-one compounds, mainly flavonoid glycosides and phenolic constituents. Molecular docking against fungal 1,3- β -glucanosyltransferase, a key enzyme involved in cell wall biosynthesis, revealed favorable binding affinities for several flavonol glycosides, particularly rhamnoside derivatives, showing binding modes comparable to the co-crystallized ligand. Structure–activity relationship analysis highlighted the importance of glycosylation patterns and rhamnose substitution for enzyme interaction. In vitro antifungal evaluation using a microbroth dilution assay demonstrated notable activity of the extract against M. circinelloides , with minimum inhibitory and fungicidal concentrations of 15.62 and 31.25 μg/mL, respectively, comparable to the reference antifungal fluconazole (MFC = 31.25 μg/mL). Collectively, these findings provide the first combined metabolomic, biological, and computational evidence supporting the antifungal potential of S. persica against M. circinelloides , while highlighting the need for further studies to isolate active constituents and validate efficacy and safety in vivo .
Amir et al. (Tue,) studied this question.