Cytotoxic constituents of the roots of Exostema acuminatum

Bioassay-guided phytochemical investigation of the roots of Exostema acumin atum (Rubiaceae) using human oral epidermoid carcinoma (KB) cells as a moni tor, led to the isolation of two norditerpenoids, namely, (16R)-ent-16,17-d ihydroxy-19-nor-kaur-4-en-3-one (1) and (16S)-ent-16,17-dihydroxy-19-nor-ka ur-4-en-3-one (2), and six previously known 4-phenylcoumarins (3-8). The st ructure and relative stereochemistry of the novel compound 1 were determine d by X-ray crystallography. All isolates were tested against a panel of hum an tumor cell lines, and the 4-phenylcoumarins showed significant cytotoxic ity, 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. (C) 2000 Elsevier Science Ltd. All rights reserved.