Comparative SAR Evaluations of Annonaceous Acetogenins for Pesticidal Activity

The activities of 44 Annonaceous acetogenins, which were originally isolated by monitoring plant fractionations with the brine shrimp lethality test (BST), were evaluated in the yellow fever mosquito larvae microtiter plate (YFM) assay. The results clearly demonstrate that most acetogenins have pesticidal properties. The structure–activity relationships indicate that the compounds bearing adjacent bis-THF (tetrahydrofuran) rings with three hydroxyl groups are the most potent. Bullatacin ( 1 ) and trilobin ( 7 ) gave the best activities against YFM with LC₅₀ values of 0·10 and 0·67 mg litre^-1, respectively. Compounds showing LC₅₀ values below 1·0 mg litre^-1 in this assay are usually considered significant as new lead candidates for pesticidal development. In the BST, the corresponding LC₅₀ values were 1·6×10^-3 ( 1 ) and 9·7×10^-3 ( 7 ) mg litre^-1. This is the first report of pesticidal structure–activity relationships for a series of Annonaceous acetogenins which are known to act, at least in part, as potent inhibitors of mitochondrial NADH: ubiquinone oxidoreductase. © of SCI.