Cytotoxic Constituents of the Roots of Exostema acuminatum

Bioassay-guided phytochemical investigation of the roots of Exostema acuminatum (Rubiaceae) using human oral epidermoid carcinoma (KB) cells as a monitor, led to the isolation of two norditerpenoids, namely, (16R)-ent-16,17-dihydroxy-19-nor-kaur-4-en-3-one (1) and (16S)-ent-16,17-dihydroxy-19-nor-kaur-4-en-3-one (2), and six previously known 4-phenylcoumarins (3–8). The structure and relative stereochemistry of the novel compound 1 were determined by X-ray crystallography. All isolates were tested against a panel of human tumor cell lines, and the 4-phenylcoumarins showed significant cytotoxicity, with 3′-hydroxy-5,7,4′-trimethoxy-4-phenylcoumarin (5) and 8-hydroxy-5,7,4′-trimethoxy-4-phenylcoumarin (6) exhibiting the most potent activity. Two of the 4-phenylcoumarins, 5,7,4′-trimethoxy-4-phenylcoumarin (3) and 6, were evaluated in an in vivo P388 murine leukemia model.