Modified Cytotoxic Terpenoids from the Tuber of <i>Icacina trichantha</i>

One highly modified polycyclic ent -kaurane dimer (bisicacinol A, 1 ), two novel C50-terpenoids (bisicacinols B and C, 2 and 3 ), three new diterpenoids (trichanthones A–C, 4 – 6 ), together with eight known analogs ( 7 – 14 ) were isolated from the tuber of Icacina trichantha . Their structures were elucidated by spectroscopic interpretation, electronic circular dichroism (ECD), and single-crystal X-ray crystallographic methods. Bisicacinol A ( 1 ) is the first ent -kaurane dimer possessing a unique 6/6/6/5/6/7 spiro-hexacyclic carbon ring system linked to a caged 3,3-dimethyl-9,10-dioxatricyclo[4.3.1.0 2,7 ]decane moiety. Bisicacinols B ( 2 ) and C ( 3 ), a pair of epimers, represent the first examples of C50-terpenoids composed of an ent -kaurane segment and an ursane moiety linked by a C-17–C-20′ single bond. Compounds 1, 2, 4, 7, 11, and 13 demonstrated potent cytotoxic activity against MIA PaCa-2 tumor cells, and 4 (IC 50 = 0.02 μM) exhibited nearly 200-fold higher activity than that of camptothecin. Additionally, 1 – 6, 8, 9, 11, and 14 displayed significant cytotoxic activity against A549 tumor cells, surpassing that of carboplatin at a concentration of 40 μM.