Mode of Action of Novel Pyrazoloquinazoline on Diamondback Moth (Plutella xylostella) Ligand-Gated Chloride Channels

J Agric Food Chem. 2023 May 17;71(19):7250-7257. doi: 10.1021/acs.jafc.3c01270. Epub 2023 May 3.

Abstract

In our previous study, a series of novel pyrazoloquinazolines were synthesized. Pyrazoloquinazoline 5a showed high insecticidal activity against the diamondback moth (Plutella xylostella) and no cross-resistance to fipronil. Patch clamp electrophysiology performed on P. xylostella pupae brains and two-electrode voltage clamp electrophysiology performed on Xenopus Laevis oocytes indicated that 5a might act on the ionotropic γ-aminobutyric acid (GABA) receptor (GABAR) and glutamate-gated chloride channel (GluCl). Moreover, 5a's potency on PxGluCl was about 15-fold higher than on fipronil, which may explain why there was no cross-resistance between 5a and fipronil. Downregulation of the PxGluCl transcription level significantly enhanced the insecticidal activity of 5a on P. xylostella. These findings shed light on the mode of action of 5a and provide important insights into the development of new insecticides for agricultural applications.

Keywords: Plutella xylostella; glutamate-gated chloride channel; mode of action; pyrazoloquinazoline; γ-aminobutyric acid receptor.

MeSH terms

  • Animals
  • Chloride Channels / genetics
  • Chlorides
  • Insecticide Resistance
  • Insecticides* / pharmacology
  • Ligand-Gated Ion Channels*
  • Ligands
  • Moths* / genetics
  • Receptors, GABA

Substances

  • Ligand-Gated Ion Channels
  • Chlorides
  • Ligands
  • Insecticides
  • Chloride Channels
  • Receptors, GABA