Modified Cytotoxic Terpenoids from the Tuber of Icacina trichantha

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-dioxatricyclo4.3.1.02,7decane 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 (IC50 = 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.