Antiproliferative steroidal glycosides from Digitalis ciliata

Abstract Two new compounds, a furostanol glycoside ( 1 ) and a pregnane glycoside ( 4 ), along with eight known compounds, belonging to the classes of spirostane ( 2 , 3 ), pregnane ( 5 – 7 ) and cardenolide ( 8 – 10 ) glycosides, were isolated from the seeds of Digitalis ciliata . Their structures were elucidated by 1D and 2D-NMR experiments as well as ESI-MS analysis. For the first time pregnane glycosides of the diginigenin series have been isolated from D. ciliata . The cytotoxic effects of compounds 1 – 10 on cell viability of several cancer cell lines, namely human breast cancer (MCF-7), human glioblastoma (T98G), human lung adenocarcinoma (A549), human colon carcinoma (HT-29), and human prostate cancer (PC-3) cell lines were evaluated. Compounds 1 , 4 , 7 and 8 showed antiproliferative effects against MCF-7, HT-29 and A549 cancer cells with IC 50 values ranging from 8.3 to 20 μM. The effects of compounds 1 – 10 on cell proliferation were evaluated on these three cancer cell lines by cell cycle analysis of DNA content using flow cytometry. Compounds 7 , 8 and 10 induced significant changes in G 2 /M cell cycle phase of all analyzed cells. The obtained results indicate that compounds 7 , 8 and 10 are cytostatic compounds effective in reducing cell proliferation by inducing accumulation of the cells in the G 2 /M phase of the cell cycle.