Cytotoxic 3,4-seco-Atisane Diterpenoids from Croton barorum and Croton goudotii

In a screening program directed to the discovery of new anticancer agents from Madagascan plants, ethyl acetate extracts of Crown barorum and C. goudotii showed strong cytotoxic activity, with 100% inhibition at 10 mu g/mL in a primary screen using the murine lymphocytic leukemia P388 cell line. Bioassay-guided fractionation led to the isolation of two new 3,4-seco-atisane diterpenoids, crotobarin (1) and crotogoudin (2). Their structures were elucidated by spectroscopic data interpretation. Compounds 1 and 2 produced a net progression in the number of cells arrested at the G2/M growth stage in the cell cycle of the K562 human leukemia cell line at 4 mu M.