Triterpenoidal saponins from the fruits of Gleditsia caspica with proapoptotic properties.

Three previously undescribed oleanane-type triterpenoidal saponins named caspicaosides L-N were isolated from the fruits of Gleditsia caspica Desf. The aglycons of these saponins were echinocystic acid, erythrodiol and 12-oleanene-3,28,30-triol. Caspicaoside L is a bisdesmosidic saponin acylated with two monoterpenic acids. It has a disaccharide moiety made up of glucose and arabinose attached to C-3 and pentasaccharide moiety linked to C-28 made up of one glucose, 2 xyloses, one inner rhamnose and one terminal rhamnose which was acylated with two identical monoterpenic acids. Caspicaoside M is a monodesmosidic saponin with a trisaccharide moiety at C-3 made up of glucose, xylose and arabinose, while caspicaoside N has a disaccharide moiety at C-3 made up of glucose and arabinose. Their structures were determined by extensive 1D and 2D (DQF-COSY, HSQC, TOCSY, H-C-HSQC-TOCSY, HMBC, ROESY, NOESY) NMR, HRESIMS analyses and chemical degradation. The cytotoxicity MTT-based assay showed that caspicaosides M, N and L, respectively, exhibited high cytotoxic activity with IC ≤ 10 μM (72 h) at least against one of the three used cancer cell lines, MCF 7, A2780 and HT 29; and were 2-34 folds selective against the normal fibroblasts (MRC 5). All compounds also induced apoptosis and caused G/M arrest in MCF 7 cells (24 h); thus showing pro-apoptotic properties.