cis-Annonacin and (2,4)-cis-and trans-isoannonacins: Cytotoxic monotetrahydrofuran annonaceous acetogenins from the seeds of Annona cherimolia

cis-Annonacin (1) and the mixture of (2,4)-cis-and trans-isoannonacins (2 a nd 3), three known mono-tetrahydrofuran an nonaceous acetogenins, have been isolated from the seeds of Annona cherimolia by the use of the brine shrim p lethality test (BST) for bioactivity directed fractionation. Their struct ures were elucidated based on spectroscopic and chemical methods. 1 showed potent cytotoxicities in the brine shrimp lethality test (BST) and among si x human solid tumor cell lines with notable selectivity for the pancreatic cell line (PaCa-2) at about 1,000 times the potency of adriamycin. The mixt ure of 2 and 3 is over 10,000 times cytotoxic as adriamycin in the pancreat ic cell line (PaCa-2). All of the compounds are about 10 to 100 times as cy totoxic as adriamycin in the prostate cell line (PC-3).