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Novel Compounds Show Promise as Safer, More Potent Insecticides

August 29, 2005

WASHINGTON, Aug. 28 “” Research teams at Nihon Nohyaku Co., Ltd., Bayer CropScience and DuPont have developed two new classes of broad-spectrum insecticides that show promise as a safer and more effective way to fight pest insects that damage food crops. The insecticides, which represent the first synthetic compounds designed to activate a novel insecticide target called the ryanodine receptor, may also help tackle the growing problem of insecticide resistance, the researchers say. They described their studies today at the 230th national meeting of the American Chemical Society, the world’s largest scientific society.

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

Targeting the ryanodine receptor may offer a promising alternative, researchers say. Ryanodine, a natural alkaloid discovered years ago in a species of tropical plant, has been used to study muscle physiology in a wide variety of organisms, including insects and mammals. Ryanodine receptors regulate muscle and nerve activities by modifying levels of internal calcium in these cells. These receptors exist in both mammals and insects but have distinct differences. Researchers have known that ryanodine itself has insecticidal properties, but no synthetic molecules had previously been identified that potently and selectively target these receptors in insects, until now.

Nihon Nohyaku Co., Ltd., based in Japan, and Bayer CropScience AG in Germany have jointly developed Flubendiamide, the first example of the phthalic acid diamides, a novel class of insecticides that activate the ryanodine receptor. The insecticide is highly effective against many different species of caterpillars, says Masanori Tohnishi, a senior research scientist at Nihon Nohyaku. In early tests, the compound showed high activity against the tobacco budworm (Heliothis virescens), which is known to cause serious damage to cotton, tobacco and other crops, the researchers say. The compound did not have any measurable effect on mammalian ryanodine receptors, according to Peter Lmmen, Ph.D., a research scientist at Bayer CropScience.

DuPont, based in Wilmington, Del., is developing another group of compounds that target the ryanodine receptor. Called anthranilic diamides, these novel compounds show excellent control of pest insects with exceptional mammalian safety, according to the researchers. They were the first to demonstrate the mode of action of these ryanodine receptor-active molecules, says Daniel Cordova, a researcher at DuPont Crop Protection.

Both classes of compounds are believed to have high potency, the researchers say, although they are structurally different. Both insecticides are still in developmental stages.

The research team at DuPont says they have cloned ryanodine receptors from several insect species and that these receptors may help provide a better understanding of their role in calcium signaling, which could lead to new insights into human diseases.

The American Chemical Society is a nonprofit organization, chartered by the U.S. Congress, with a multidisciplinary membership of more than 158,000 chemists and chemical engineers. It publishes numerous scientific journals and databases, convenes major research conferences and provides educational, science policy and career programs in chemistry. Its main offices are in Washington, D.C., and Columbus, Ohio.

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