Synthesis and biological evaluation of oleanolic acid derivatives as potential c-kit inhibitors

The 3-O-(4'-imidazole)-12-en-olean-28-amide derivatives 7-1 to 7-11 through modification the C-3 and C-28 of the natural product oleanolic acid were prepared, and their structures were confirmed by MS,¹H NMR and ¹³C NMR. The antitumor activities of these compounds against breast cancer MCF-7 and gastric cancer SGC7901 cells in vitro were determined by MTT assay. Cell tests showed that the antitumor activities of compound 7-10 exhibited significant antitumor activity which was equivalent to the positive control drug nilotinib, and the affinity was verified by molecular dynamics experiment in vitro. Molecular docking showed that compound 7-10 have high binding ability with c-kit. Therefore, compound 7-10 has the potential to become a new c-kit inhibitor, which deserves further research.