Synthesis and cytotoxicity of novel ursolic acid derivatives containing an acyl piperazine moiety

This study designed and synthesized a series of novel ursolic acid derivatives in an attempt to develop potent antitumor agents. Their structures were confirmed using MS, IR, 1H NMR and 13C NMR. The inhibitory activities of the title compounds against the MGC-803 (gastric cancer cell) and Bcap-37 (breast cancer cell) human cancer cell lines were evaluated using standard MTT assay in vitro. The pharmacological results showed that some of the compounds displayed moderate to high levels of antitumor activities against the tested cancer cell lines and that most exhibited more potent inhibitory activities compared with ursolic acid. The mechanism of compound 4b was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, TUNEL assay and flow cytometry, which revealed that the compound can induce cell apoptosis in MGC-803 cells.

Graphical abstractA series of new ursolic acid derivatives containing an acyl piperazine moiety were synthesized, and were found possessing good antitumor activities as well as cell apoptosis inducing activities in MGC-803 cells.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A series of new ursolic acid derivatives containing acyl piperazine were synthesized. ► The new compounds showed good antiproliferative activities against tumor cells. ► Further mechanism study indicates that the new compounds can induce cell apoptosis.