Characterization of a nicotinic acetylcholine receptor binding site for sulfoxaflor, a new sulfoximine insecticide for the control of sap-feeding insect pests.

Sulfoxaflor (SFX, Isoclast™ Active) is a recently developed sulfoximine insecticide that is highly effective against sap-feeding insect pests. SFX has been shown to act through an interaction with insect nicotinic acetylcholine receptors (nAChRs). SFX was previously found to interact weakly with the binding site for the neonicotinoid imidacloprid. However, radioligand displacement studies characterizing the binding site of the insecticide SFX itself have not been conducted. In this study, we report the characterization of a high affinity [3H]SFX Myzus persicae (green peach aphid, GPA) binding site with relatively low abundance. Through the evaluation of a set of SFX analogs, we have demonstrated that displacement of [3H]SFX shows an excellent correlation with GPA toxicity, and thus is toxicologically relevant. Comparison with the previously described methyl-SFX binding site information reveals differences with the SFX binding site that are discussed herein. [3H]SFX therefore represents a new tool for the characterization of insect nAChRs.

Discovery of the aryl heterocyclic amine insecticides: synthesis, insecticidal activity, field results, mode of action and bioavailability of a leading field candidate.

BACKGROUND: γ-Amino butyric acid (GABA) antagonists are proven targets for control of lepidopteran and other pests. New heterocyclic compounds with high insecticidal activity were discovered using a competitive-intelligence-inspired scaffold-hopping approach to generate analogs of fipronil, a known GABA antagonist. These novel aryl heterocyclic amines (AHAs) displayed broad-spectrum activity on a number of chewing insect pests. RESULTS: Through >370 modifications of the core AHA structure, a 7-pyrazolopyridine lead molecule was found to exhibit much improved activity on a number of insect pests. In field trial studies, its performance was 2-4 times lower than commercial standards and also appeared to be species dependent, with good activity seen for larvae of Spodoptera exigua, but inactivity on larvae of Trichoplusia ni. CONCLUSION: An extensive investigational biology effort demonstrated that these AHA analogs appear to have multiple modes of action, including GABA receptor antagonism and mitopotential or uncoupler activity. The limited capability in larvae of T. ni to convert the lead molecule to its associated open form correlates with the low toxicity of the lead molecule in this species. This work has provided information that could aid investigations of novel GABA antagonists. © 2016 Society of Chemical Industry.