Antiproliferative Bufadienolides from the Bulbs of Drimia altissima

The bulbs of the South African Drimia altissima (Asparagaceae or Hyacinthaceae sensu APGII) have yielded a range of previously undescribed bufadienolides, drimianins A-G ( 1 - 7 ), the known bufadienolides bovogenin A ( 8 ), 3β- O- β-d - glucopyranosylbovogenin A ( 9 ), scillaren F ( 10 ), and altoside ( 11 ), the known homoisoflavonoid (3 S ) - 3-(4'-methoxybenzyl)-5,6,7-trimethoxychroman-4-one (urgineanin C), the sesquiterpenoids 1β,6α-dihydroxy-4(15)-eudesmene and 6α-hydroxy-4(15)-eudesmen-1-one, polybotrin, adenosine, and 9 R -hydroxy-(10 E ,12 Z )-octadecadienoic acid ethyl ester. The bufadienolides isolated were tested at 10 μM in the NCI-60 cancer cell screen, and nine of these were selected for further screening at five concentrations. Drimianins C ( 3 ) and E ( 5 ) showed activity at the nanomolar level against a number of human cancer cell lines in the NCI-60 screen.