Chemical modifications of ergostane-type triterpenoids from Antrodia camphorata and their cytotoxic activities

In order to discover potential antitumor agents from natural products, chemical modifications of ergostane-type triterpenoids from Antrodia camphorata yielded ten new compounds. They include nine C-26 amide derivatives of antcin G (1) and a methyl antcin B (4) derivative with hydroxyamino groups at C-3 and C-7. Chemical structures of the new compounds were elucidated by NMR and MS analyses. Furthermore, cytotoxicities of the triterpenoid derivatives were evaluated using four human cancer cell lines (HL60, U251, SW480, and MCF-7). As a result, 1a, 1g, and 4a exhibited potent cytotoxic activities against HL60, U251, and SW480 with IC50 values of 0.7 +/- 0.9, 2.9 +/- 1.3, and 2.2 +/- 0.6 mu M, respectively. Molecular docking indicates that 1a, 1g, and 4a have strong binding affinity with DNA topoisomerase II alpha (-9.3, -7.9, and -7.4 kcal/mol, respectively), and that they could be potent topoisomerase II alpha inhibitors.