Design, Synthesis And Preliminary Activity Of Solasodine Glycoside

Steroidal saponins, a class of important natural products, are widely found in terrestrial plants and some marine organisms. Some of the steroidal saponins exhibit moderated to good cardiovascular, antitumor, antifungal, and immunostimulant activities. The bioactivity is not only related with the aglycon, but also the carbohydrate residues. The nature, number, and order of attachment of the sugars in the oligosaccharide associated with the steroidal saponins are crucial for the biological activities. Solasodine glycoside, such as solamargine, has been proved to be a very important anti-cancer agent and it is closely related to the rhamonse. In order to discover more potent cytotoxic agents and explore the preliminary structure activity relationship, a new series of solasodine glycosides2-9were synthesized via a transglycosylation strategy, and their cytotoxic activity against a panel of human cancer cell lines (MCF-7, KB, K562, and PC3cells) were evaluated by MTT assay. The results indicated that compounds2,8, and9with the substitute moiety of rhamnose,2-hydroxyethoxymethyl, and1,3-dihydroxypropan-2-yloxy-methyl, respectively, exhibited quite strong anticancer activity. The underlying mechanism test demonstrated that these compounds could induce apoptosis as detected by DAPI staining, and Annexin V and propidium idodide binding. Cell cycle analysis indicated that the cancer cells were predominantly arrested at G2/M phase when exposure to these compounds as examined by flow cytometry. These compounds may serve as lead candidates in the development of novel chemotherapeutics for cancer treatment.