LAUSR

Bioassay-guided investigation of Panicum turgidum extract resulted in the identification of seven steroidal saponins (Turgidosterones 1–7). They were evaluated for their in vitro antifungal, antileishmanial, and antitrypanosomal activities. Turgidosterone 6 was the most active antifungal against Candida albicans and Candida neoformans (IC50 values of 2.84 and 1.08 μg mL−1, respectively). Turgidosterones 4–7 displayed antileishmanial activity against Leishmania donovani promastigotes with IC50 values ranging from 4.95 to 8.03 μg mL−1 and against Leishmania donovani amastigote/THP with IC50 values range of 4.50–9.29 μg mL−1. Activity against Trypanosoma brucei was also observed for Turgidosterones 4–7 with an IC50 values range of 1.26–3.77 μg mL−1. Turgidosterones 1–3 did not display any activity against the tested pathogens. The study of structure–activity relationships of the isolated saponins indicated that the antifungal, antileishmanial, and antitrypanosomal activities are markedly affected by the presence of spirostane-type saponins and the elongation of the sugar residue at C-3. To quantitatively determine the most abundant active ingredient in Panicum turgidum extract, a single run, sensitive, and highly selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been applied under positive and negative modes. The obtained results showed that compound 5 was the most abundant (95.93 ± 1.10 mg per gram of dry Panicum turgidum extract), followed by 6 (52.51 ± 1.05 mg gm−1), 4 (32.71 ± 0.48 mg gm−1), and 7 (13.19 ± 0.50 mg gm−1). Docking of these saponins against the Candida albicans oxidoreductases and Leishmania infantum trypanothione reductase active sites revealed their potential to effectively bind with a number of key residues in both receptor targets.