Cytotoxic diterpenoids from the leaves and stem bark of Croton haumanianus (Euphorbiaceae)

The leaf extract of Croton haumanianus J. Leonard (Euphorbiaceae) yielded twenty-six compounds, including eight previously reported ent-kauranes and an ent-labdane and eight undescribed ent-kauranes, ent-16R-kauran-17-al, ent-3 beta-hydroxy-16R-kauran-17-al, ent-16S,17-epoxykauran-19-ol, ent-16S,17-epoxykauran-3 beta-ol, ent-17-palmityloxykaurane-3 beta,16 beta-diol, ent-17-palmityloxykauran-16 beta-ol, ent-3 alpha,18-cyclokaurane-16 beta,17-diol and 19-nor-16 alpha,17-dihydroxy-ent-kaur-4(18)-ene and three undescribed ent-clerodanes, dimethyl ent-15,16-epoxy-6bhydroxy-1,3,13(16),14-clerodatetraen-20,12S-olide-18,19-dioate (saniolide A), dimethyl ent-15,16-epoxy-6 beta-hydroxy-1,3,13(16),14-clerodatetraen-20,12R-olide-18,19-dioate (12-epi-saniolide A), methyl ent-15,16-epoxy-1,3,13(16),14-clerodatetraen-18,6R:20,12S-diolide-19-oate (saniolide B). The stem bark extract yielded the ent-clerodane crotocorylifuran, and five undescribed ent-isopimaranes, ent-isopimara-8(14),15-dien-18-al, ent-18-hydroxyisopimara-8(14),15-dien-7-one, ent-isopimara-7,15-dien-18-oic acid, ent-isopimara-7,15-dien-18-ol and ent-isopimara-8,15-dien-7-oxo-18-oic acid. Three compounds, ent-kaurane-3 beta,16 beta,17-triol, ent-17-palmityloxykaurane-3 beta,16 beta-diol and ent-17-palmityloxykauran-16 beta-ol, showed selective activity against three of the NCI 60 cancer cell lines, the colon (HCT-116), the melanoma (M14) and the renal (786-0) cancer cell lines at a concentration of 10(-5) M.