Triterpenoid saponins from the cytotoxic root extract of Sideroxylon foetidissimum, an endemic Yucatecan medicinal plant

The flora of the Yucatan peninsula (Mexico) includes approximately 3000 plant species. Sideroxylon foetidissimum Jacq. subsp. gaumeri (Sapotaceae) is an endemic plant to the Yucatan peninsula; its fruit is edible and local people use the plant for medicinal purposes, although no details on its preparation or application are available [1,2]. A preliminary cytotoxic evaluation of the ethanolic root extract of S. foetidissimum revealed a potent activity against murine macrophage like cell line RAW 264.7 (IC50=39.54±4.11µg/mL). The systematic bioassay-guided fractionation of the extract resulted in the identification of the active saponin-containing fraction (IC50=33.69±6.19µg/mL). Four new triterpenoid saponins and a 1:1 mixture of two saponins were isolated from the active saponin- containing fraction. The evaluation of their cytotoxic activity revealed no activity for the tested pure saponins; however, the 1:1 mixture of saponins showed a potent activity (IC50=11.91±1.49µg/mL). The isolation of the saponins was carried out using semi-preparative HPLC. The structural assignments of the pure saponins were based on 1D (1H and 13C and DEPT-135) and 2D (COSY, HMBC, HSQC and TOCSY) NMR and mass spectrometry analyses. In this presentation, the isolation, identification and cytotoxic activity of the isolated compounds is discussed in more detail.

Differential cytotoxic and prooxidnant activity of knipholone and knipholone anthrone

Knipholone (KP) and knipholone anthrone (KA) are natural 4-phenylanthraquinone structural analogues with established differential biological effects including in vitro antioxidant [1] and antimicrobial properties [2]. The present study was designed to investigate the comparative in vitro cytotoxic activity and the possible mechanism of action of these two compounds. We demonstrated that KA is by order of magnitude more cytotoxic to mammalian cells than KP. In parallel with the demonstrated cytotoxic effect, KA but not KP induces prooxidative DNA damage in the presence of copper ions. In order to establish the possible involvement of reactive oxygen species in the KA-mediated prooxidative effect, we investigated the protective effect of several metal chelators and reactive oxygen species scavengers. Our data suggest that reactive oxygen species such as hydrogen peroxide are involved and a good correlation between prooxidative action, antioxidant effect and cytotoxicity is established for these two structural analogues. The chemistry, pharmacology and potential medicinal/toxicological potential of these compounds are discussed.