Abstract
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, antileishmaniat and antitrypanosomal activities. Turgidosterone 6 was the most active antifungal against Candida albicans and Candida neoformans (IC50 values of 2.84 and 1.08 mu g mL(-1), respectively). Turgidosterones 4-7 displayed antileishmanial activity against Leishmania donovani promastigotes with IC50 values ranging from 4.95 to 8.03 mu g mL(-1) and against Leishmania donovani amastigote/THP with IC50 values range of 4.50-9.29 mu g mL(-1). Activity against Trypanosoma brucei was also observed for Turgidosterones 4-7 with an IC50 values range of 1.26-3.77 mu g 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, antileishmaniat 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.