Synthesis and evaluation as potential antitumor agents of novel ursolic acid derivatives

摘要

Novel ursolic acid derivatives were synthesized, and their structures were confirmed by MS, IR, H-1 NMR and C-13 NMR spectral analysis. In vitro antitumor activities of these compounds against MGC-803 (gastric cancer cell) and Bcap-37 (breast cancer cell) human cancer cell lines were evaluated by MTT assay. The pharmacological screening results revealed that many derivatives exhibited moderate to high activities against the tested cell lines, and that most demonstrated more potent inhibitory activities than that of ursolic acid. Preliminarily mechanism study of representative compound 3h were carried out by acridine orange/ethidium bromide staining, Hoechst 33258 staining, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay, and flow cytometry which indicated that compound 3h can induce cell apoptosis of MGC-803 cells, and the apoptosis ratio reached 34.59 % after 36 h treatment at 10 mu M.