Saponins from Oxybasis rubra (L.) S.Fuentes, Uotila & Borsh: Comparative Assessment of Cytotoxic Potential Against a Wide Panel of Cancer Cell Lines

Two triterpene saponins, hederagenin glucosides, including a novel monodesmoside: 3-<i>O</i>-β-D-glucopyranosyl(1→3)-β-D-glucopyranosyl] hederagenin (compound <b>1</b>), were isolated from the fruits of <i>Oxybasis rubra</i> (L.) S.Fuentes, Uotila & Borsh (Amaranthaceae). These compounds, together with hederagenin itself (compound <b>4</b>) and a commercially available 28-<i>O</i>-β-D-glucopyranosyl hederagenin ester (compound <b>3</b>), were evaluated for cytotoxicity and selectivity across a wide panel of human cancer cell lines (skin, prostate, gastrointestinal, thyroid, and lung). All four compounds exhibited dose- and time-dependent effects, with varying potency depending on the specific cancer type. The isolated bidesmosidic saponin (3-<i>O</i>-β-D-glucopyranosyl(1→3)-β-D-glucopyranosyl] hederagenin 28-<i>O</i>-β-D-glucopyranosyl ester-compound <b>2</b>) showed the strongest activity and selectivity, with an IC₅₀ = 6.52 μg/mL after 48 h incubation against WM793 melanoma, and almost no effect on normal HaCaT skin cells (IC₅₀ = 39.94 μg/mL). Multivariate analysis of the obtained data using principal component analysis (PCA) and hierarchical cluster analysis (HCA) supported the assumption that cytotoxicity is influenced by the type of compound, its concentration, and the intrinsic sensitivity of the cell line. Structure-activity observations between closely related hederagenin derivatives are also briefly presented.