Flupyrimin: A Novel Insecticide Acting at the Nicotinic Acetylcholine Receptors

  • J Agric Food Chem. 2017 Sep 13;65(36):7865-7873. doi: 10.1021/acs.jafc.7b02924.
Yasumichi Onozaki  1 ,  Ryo Horikoshi  1 ,  Ikuya Ohno  1 ,  Shigeki Kitsuda  1 ,  Kathleen A Durkin  2 ,  Tomonori Suzuki  3 ,  Chiaki Asahara  3 ,  Natsuko Hiroki  3 ,  Rena Komabashiri  3 ,  Rikako Shimizu  3 ,  Shogo Furutani  4 ,  Makoto Ihara  4 ,  Kazuhiko Matsuda  4 ,  Masaaki Mitomi  1 ,  Shinzo Kagabu  5 ,  Katsuhito Uomoto  1 ,  Motohiro Tomizawa  3
Affiliations
  • 1. Agricultural and Veterinary Research Laboratories, Agricultural and Veterinary Division, Meiji Seika Pharma Co., Ltd. , Yokohama, Kanagawa 222-8567, Japan.
  • 2. College of Chemistry, University of California , Berkeley, California 94720-1460, United States.
  • 3. Faculty of Life Sciences, Tokyo University of Agriculture , Setagaya, Tokyo 156-8502, Japan.
  • 4. Faculty of Agriculture, Kindai University , Nara 631-8505, Japan.
  • 5. Faculty of Education, Gifu University , Gifu 501-1193, Japan.
PMID: 28820587 DOI: 10.1021/acs.jafc.7b02924
Abstract

A novel chemotype Insecticide flupyrimin (FLP) [N-[(E)-1-(6-chloro-3-pyridinylmethyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide], discovered by Meiji Seika Pharma, has unique biological properties, including outstanding potency to imidacloprid (IMI)-resistant rice pests together with superior safety toward pollinators. Intriguingly, FLP acts as a nicotinic antagonist in American cockroach neurons, and [3H]FLP binds to the multiple high-affinity binding components in house fly nicotinic acetylcholine (ACh) receptor (nAChR) preparation. One of the [3H]FLP receptors is identical to the IMI receptor, and the alternative is IMI-insensitive subtype. Furthermore, FLP is favorably safe to rats as predicted by the very low affinity to the rat α4β2 nAChR. Structure-activity relationships of FLP analogues in terms of receptor potency, featuring the pyridinylidene and trifluoroacetyl pharmacophores, were examined, thereby establishing the FLP molecular recognition at the Aplysia californica ACh-binding protein, a suitable structural surrogate of the insect nAChR. These FLP pharmacophores account for the excellent receptor affinity, accordingly revealing differences in its binding mechanism from IMI.

Keywords
flupyrimin; nicotinic acetylcholine receptor; nicotinic insecticide; pyridinylidene and trifluoroacetyl pharmacophores.
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