Differential inhibition by castanospermine of various insect disaccharidases

Abstract

The indolizidine alkaloid, castanospermine (1,6,7,8-tetrahydroxy-octahydroindolizidine—a stereochemical mimic of glucose found in the Australian legumeCastanospermum australe), differentially inhibited cellobiose, lactose, maltose, sucrose, and trehalose hydrolyzing enzymes from a broad taxonomic spectrum of insects (19 species from 12 different families). It was a potent inhibitor of cellobiase activity of all insects tested (50% inhibition at <3.2 × 10⁻⁵ M castanospermine). With one exception, it also inhibited lactase activity of all insects examined. Only in the sap-feeding Homoptera did castanospermine inhibit all disaccharidase activities assayed. Trehalase activity of the Lepidoptera and Diptera was generally inhibited by castanospermine, whereas inhibition of trehalase activity of the Coleoptera by castanospermine was exiguous or not detectable. Castanospermine was a significant feeding deterrent towards pea aphids,Acyrthosiphon pisum, with an ED₅₀ of 1 × 10⁻⁴ M in artificial diets. Two compounds stereochemically related to castanospermine, deoxynojirimycin and 6-epicastanospermine, were each slightly active at deterring the feeding of green peach aphids,Myzus persicae, (ED₅₀=2.5 × 10⁻³ M) and greenbugs,Schizaphis graminum (ED₅₀=5 × 10⁻³ M), respectively. Among the insects studied there was no distinct relationship between enzyme inhibition and adaptation to host plants containing castanospermine or other toxic alkaloids.