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

Abstract

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[4.3.1.02,7]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 (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.