2. Academic Validation
  3. Flupyrimin: A Novel Insecticide Acting at the Nicotinic Acetylcholine Receptors

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

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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