One-pot synthesis, anti-tumor evaluation and structure-activity relationships of novel 25-OCH-PPD derivatives.

Based on the fact that 25-OCH-PPD, a natural ginsengenin isolated from the leaves of , is a promising lead compound, novel 25-OCH-PPD derivatives were synthesized to find more potent anti-tumor agents by a simple and facile synthetic method. These derivatives were classified into three types and screened for their cytotoxic activities against seven human cancer cell lines. Compared with 25-OCH-PPD, compounds , , and exhibited higher anti-tumor activities on all tested cell lines with almost 5-fold to 15-fold increases. In particular, compound showed the greatest cytotoxic activity against α-2 cells (IC = 2.4 ± 0.4 μM). The preliminary study on the mechanisms indicated that compound could induce α-2 cell apoptosis. Structure-activity relationships demonstrated that the carbon-carbon double bond at the C-20 position could enhance the antiproliferative activity. In conclusion, the novel derivatives , , and could be further studied as potential candidates for the treatment of cancer. This research provides a theoretical reference for the exploration of new antiproliferative agents.