Novel Compounds Show Promise As Safer, More Potent Insecticides

Many of the most widely used insecticidestoday act on only a handful of exploited targets, including theorganophosphates, which block acetylcholinesterase, an enzyme thathelps control nerve activity. Some experts are concerned that theseolder, less-selective insecticides could pose heath risks and there’s agrowing effort underway to find safer replacements.

Targeting theryanodine receptor may offer a promising alternative, researchers say.Ryanodine, a natural alkaloid discovered years ago in a species oftropical plant, has been used to study muscle physiology in a widevariety of organisms, including insects and mammals. Ryanodinereceptors regulate muscle and nerve activities by modifying levels ofinternal calcium in these cells. These receptors exist in both mammalsand insects but have distinct differences. Researchers have known thatryanodine itself has insecticidal properties, but no syntheticmolecules had previously been identified that potently and selectivelytarget these receptors in insects, until now.

Nihon Nohyaku Co.,Ltd., based in Japan, and Bayer CropScience AG in Germany have jointlydeveloped Flubendiamide, the first example of the phthalic aciddiamides, a novel class of insecticides that activate the ryanodinereceptor. The insecticide is highly effective against many differentspecies of caterpillars, says Masanori Tohnishi, a senior researchscientist at Nihon Nohyaku. In early tests, the compound showed highactivity against the tobacco budworm (Heliothis virescens), which isknown to cause serious damage to cotton, tobacco and other crops, theresearchers say. The compound did not have any measurable effect onmammalian ryanodine receptors, according to Peter Lümmen, Ph.D., aresearch scientist at Bayer CropScience.

DuPont, based inWilmington, Del., is developing another group of compounds that targetthe ryanodine receptor. Called anthranilic diamides, these novelcompounds show excellent control of pest insects with exceptionalmammalian safety, according to the researchers. They were the first todemonstrate the mode of action of these ryanodine receptor-activemolecules, says Daniel Cordova, a researcher at DuPont Crop Protection.

Bothclasses of compounds are believed to have high potency, the researcherssay, although they are structurally different. Both insecticides arestill in developmental stages.

The research team at DuPont saysthey have cloned ryanodine receptors from several insect species andthat these receptors may help provide a better understanding of theirrole in calcium signaling, which could lead to new insights into humandiseases.

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