Pellitorine toxicity

Five isobutylamides were isolated as insect growth inhibitors and toxicants from Fagara macrophylla and identified from their spectroscopic and chemical data. Synthesis and bioassay of the five natural products plus four analogs showed pellitorine to be the most active against a variety of insects, but not against a species of snail. 

Through a comparison of the activities of the nine natural and synthetic compounds in Table I, certain functionalities appeared to be important in the efficacy of the isobutylamides to inhibit the growth of the lepidopterous larvae. These functionalities included the chain length, presence of the methylenedioxy moiety, the number of the side chain double bonds, and the stereochemistry of the side chain. Combinations of these functionalities would likely enhance the activity. For instance, Miyakado et al.H found that addition of the methylenedioxy moiety to pellitorine (4) increased its toxicity when topically applied to adults of the beetle, Callosobruchus chinensis. 

Pellitorine (4) has long been known for its toxicity when topically applied to adults of the beetle, Tenebrio molitor We found that 10 pg doses of topically applied pellitorine caused a paralytic action on adults of the confused flour beetle, Tribolium confusum (unpublished data). However, all of the affected beetles recovered within 24 hrs posttreatment. Similar topical applications of up to 20 pg/beetle of fagaramide (2.), piperlongumine ( ), and N-isobutyl-2E,4E-octadienamide ( ) proved ineffective. 

The lethal activity of the isobutylamides on C. pipiens is shown in Table II. The amides were dissolved in 0.1% acetone in distilled water to give concentrations of 1-20 ppm. Third-instar C. pipiens were transferred (5 larvae/10 ml test solution) into 1 oz. plastic cups using a 1 x 1-inch circle of ordinary window screen. Each treatment was replicated 4 times and the minimum concentration of each compound which caused 100% mortality (LDioo) within 48 h at 25 C and 16L/8D photoperiod was determined. In a result similar to that found with the artificial diet bioassay with lepidopterous larvae, pellitorine proved to be the most toxic of the assayed amides (LDjqq = 5 ppm). 

The insecticidal activity of aliphatic amides such as pellitorine, 5, is limited, at least in part, by their instability [81]. The presence of an aromatic ring at the distal end of a dienoic acid isobutylamide of suitable chain length, as in dihydropipercide, confers increased stability and enhanced insect toxicity. Structure-activity studies by Miyakado et al. [81,82,127] based on the aromatic amide dihydropipercide as lead compound and with C. chinensis males as the test insects, led to the following general conclusions ... 

Multiple activities have been observed for extracts of Zanthoxylum xanthoxyhides, a widely used medicinal plant. The principal active compounds are the isobutylamides pellitorine (IV) and fagaramide (V), which display termite and lepidopteran feeding deterrent activities. The insecticide activity of isobutylamides isolated from various plant families, has been previously investigated (11) and their level of activity has warranted patent applications. We have demonstrated also that these compoxmds may act as feeding deterrents in addition to their toxicity properties. 

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