Spiroindolines identify the vesicular acetylcholine transporter as a novel target for insecticide action.

PloS One
Ann SluderFergus G P Earley

Abstract

The efficacy of all major insecticide classes continues to be eroded by the development of resistance mediated, in part, by selection of alleles encoding insecticide insensitive target proteins. The discovery of new insecticide classes acting at novel protein binding sites is therefore important for the continued protection of the food supply from insect predators, and of human and animal health from insect borne disease. Here we describe a novel class of insecticides (Spiroindolines) encompassing molecules that combine excellent activity against major agricultural pest species with low mammalian toxicity. We confidently assign the vesicular acetylcholine transporter as the molecular target of Spiroindolines through the combination of molecular genetics in model organisms with a pharmacological approach in insect tissues. The vesicular acetylcholine transporter can now be added to the list of validated insecticide targets in the acetylcholine signalling pathway and we anticipate that this will lead to the discovery of novel molecules useful in sustaining agriculture. In addition to their potential as insecticides and nematocides, Spiroindolines represent the only other class of chemical ligands for the vesicular acetylcholine t...Continue Reading

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Citations

Jun 27, 2013·Parasitology International·Paula Ribeiro, Nicholas Patocka
Dec 15, 2015·Chemistry : a European Journal·Michael J JamesWilliam P Unsworth
Jul 7, 2015·Journal of Agricultural and Food Chemistry·Gaolei WangXiaoyong Xu
Dec 15, 2015·Journal of Neurophysiology·Francesca CashRichard A Baines
Oct 1, 2015·Molecular Diversity·Tetyana L PavlovskaDmytro V Atamanuk
Aug 24, 2020·Pesticide Biochemistry and Physiology·M GuestA J Flemming
May 26, 2021·Molecular Systems Biology·Adam McDermott-RouseAndré E X Brown

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Datasets Mentioned

BETA
FR852384
FR852389
FR852385
FR852386
FR852387

Methods Mentioned

BETA
Assay
PCR
transgenic

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