Screening of crude extracts of the bark of Annona bullata showed cytotoxic and pesticidal activities. By monitoring with brine-shrimp lethality, two novel, extremely potent acetogenins, bullatacin [1] and bullatacinone [2], were isolated. Spectral and chemical methods identified bullatacin as a diastereomer of asimicin. Bullatacinone represents bullatacin with the lactone cleaved and reformed at the 4-OH. Compounds 1 and 2 show selective cytotoxicities in human tumor cell lines, and certain susceptible cells give ED50 values as low as 10(-12)-10(-15) micrograms/ml. Bullatacin was pesticidal at concentrations as low as 1 ppm, but bullatacinone lacked pesticidal activities. The known compounds liriodenine and (-)-kaur-16-en-19-oic acid were also isolated and were lethal to brine shrimp but were not significantly cytotoxic.

Activity-directed fractionation of the stem bark of Annona squamosa, monitoring with brine shrimp lethality, led to the isolation of the highly bioactive acetogenins bullatacin [1] and bullatacinone [2], thus demonstrating a new abundant plant source for these potent compounds. A new keto-monotetrahydrofuran acetogenin with a ketolactone terminus, as first seen in bullatacinone [2], was also isolated, characterized by spectral analyses, and named squamone [3]. The cytotoxicities of 3 were increased significantly by reduction of the two keto groups to hydroxyls, and the tetrahydrosquamone [7] and bullatacinone [2] both showed selective cytotoxicities to MCF-7 human breast carcinoma. Liriodenine and (-)-kaur-16-en-19-oic acid were also isolated.