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An ethanolic extract of the leaves of Annona muricata was shown to be toxic to adult forms of the snail Biomphalaria glabrata (LC50 9.32 microg mL(-1)) and to larvae of the brine shrimp Artemia salina (LC50 0.49 microg mL(-1)). Activity-guided fractionation of the extract gave rise to a sample with high molluscicidal activity that contained the acetogenins, annonacin (90%), isoannonacin (6%) and goniothalamicin (4%).

A novel acetogenin, cis-bullatencin, was isolated by successive chromatography of a cyclohexane extract of Uvaria chamae P. Beauv. roots. The structure was elucidated by a combination of chemical and spectroscopic methods (NMR, MS). Eight known mono-THF acetogenins--bullatencin, annotemoyin-1, solamin, uvariamicin-I, -II, -III, cis-reticulatacin and cis-uvariamicin-I--were also obtained.

The acetogenins of Annonaceae are known by their potent cytotoxic activity. In fact, they are promising candidates as a new future generation of antitumoral drugs to fight against the current chemiotherapic resistant tumors. The main target enzyme of these compounds is complex I (NADH:ubiquinone oxidoreductase) of the mitochondrial respiratory chain, a key enzymatic complex of energy metabolism. In an attempt to characterize the relevant structural factor of the acetogenins that determines the inhibitory potency against this enzyme, we have prepared a series of bis-tetrahydrofuranic acetogenins with different functional groups along the alkyl chain. They comprise several oxo, hydroxylimino, mesylated, triazido, and acetylated derivatives from the head series compounds rolliniastatin-1, guanacone, and squamocin. Our results suggest a double binding point of acetogenins to the enzyme involving the alpha,alpha'-dihydroxylated tetrahydrofuranic system as well as the alkyl chain that links the terminal alpha, beta-unsaturated-gamma-methyl-gamma-lactone. The former mimics and competes with the ubiquinone substrate. The latter modulates the inhibitory potency following a complex outline in which multiple structural factors probably contribute to an appropriate conformation of the compound to penetrate inside complex I.