Design, synthesis and antitumor activity of pentacyclic triterpenoid ursolic acid derivatives and oleanolic acid derivatives based on multi-target

Totally twelve inhibitors of Survivin and Sp1 based on ursolic acid (UA) derivatives and oleanolic acid (OA) derivatives were designed and synthesized with modification at C-2, C-3 and C-28 of UA and OA. Their structures were confirmed by HRMS,1H NMR and 13C NMR. In vitro activity assay showed that these compounds can inhibit cell proliferation of HeLa, SKOV3, BGC-823 and HT1080 cells, especially compounds IV and X showed better inhibitory activity on these tumor cells than that of the positive control drug Gefitinib and similar to Vp-16. Mechanistically, selected compound may inhibit the proliferation of SKOV3 cells and trigger apoptosis by activating Sp1 to inhibit Survivin protein expression, which may be promising leading compounds for cancer therapy.