Investigating the mode of action of sulfoxaflor: a fourth‐generation neonicotinoid

Cutler, Penny; Slater, Russell; Edmunds, Andrew; Maienfisch, Peter; Hall, Roger G.; Earley, Fergus G.P.; Pitterna, Thomas; Pal, Sitaram; Paul, Verity-Laura; Goodchild, Jim; Blacker, Melissa; Hagmann, Leonhard; Crossthwaite, Andrew J.

doi:10.1002/ps.3413

Cited by 112 publications

(80 citation statements)

References 38 publications

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“…More recently, it has been found that 3 [H]‐methyl‐sulfoxaflor labels a receptor in Myzus membranes with an affinity of 83 p m , which appears to be toxicologically relevant, but distinct from the imidacloprid high affinity binding site. Thiamethoxam bound to this site with a K i of 481 n m , which was at least 100× weaker than all other commercial neonicotinoids . In summary, these results show that while thiamethoxam binds weakly to nicotinic receptors, its insecticidal activity is due to its conversion to the much more potent nicotinic agonist clothianidin in plants and insects, making it an obligate proinsecticide.…”

Section: Examples Of Proinsecticides (Organized By Irac Group)mentioning

confidence: 79%

Chance and design in proinsecticide discovery

Salgado

David

2017

Pest Management Science

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Many insecticides are inactive on their target sites in the form that is sold and applied, needing first to be bioactivated. This proinsecticide strategy has often been achieved by design, through systematic derivatization of intrinsically active molecules with protecting groups that mask their toxic effects until their selective removal in target insects by metabolic enzymes generates the toxiphore. Proinsecticides can be designed to gain selectivity between target and non-target organisms, or to improve bioavailability by enhancing plant or insect uptake. In most cases, however, chance trumps design in proinsecticide discovery: most first-in-class products that we now know to be proinsecticides were only discovered a posteriori to be such, often after having been on the market for years. Knowing the active form of an insecticide is essential to mode of action identification, and early mode of action studies on novel chemotypes should take into account the possibility that the compounds might be proinsecticides. This paper reviews examples of proinsecticides in the marketplace, strategies for making proinsecticides and techniques for unmasking proinsecticides in mode of action studies. Our analysis of global agrochemical sales data shows that 34% of the dollar value of crop insecticides used in 2015 were proinsecticides. © 2016 Society of Chemical Industry.

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Section: Examples Of Proinsecticides (Organized By Irac Group)mentioning

confidence: 79%

Chance and design in proinsecticide discovery

Salgado

David

2017

Pest Management Science

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“…The fact that SFX only interacts at the high affinity IMI binding site and has much reduced ability to interact at the second lower affinity IMI binding site, explains the relative weakness of SFX to displace [ 3 H]-IMI under standard assay conditions. 118,119) 54) This novel systemic insecticide for sucking pest control was identified by stepwise chemical evolution of the enaminocarbonyl pharmacophore inspired by existing nAChR ligands [120][121][122] and also recognized as a recurrent motif of natural products such as stemofoline, another botanical insecticide. 123,124) Flupyradifurone modulates insect nAChRs at the orthosteric binding site potently displacing [ 3 H]-IMI bound to M. domestica crude membranes with low nM affinity (IC 50 =2.38±1.93 nM).…”

Section: Sulfoximinesmentioning

confidence: 99%

The invertebrate pharmacology of insecticides acting at nicotinic acetylcholine receptors

Crossthwaite

Bigot

Camblin

et al. 2017

Journal of Pesticide Science

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The nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel composed of 5 protein subunits arranged around a central cation selective pore. Several classes of natural and synthetic insecticides mediate their effect through interacting at nAChRs. This review examines the basic pharmacology of the neonicotinoids and related chemistry, with an emphasis on sapfeeding insects from the order Hemiptera, the principle pest target for such insecticides. Although the receptor subunit stoichiometry for endogenous invertebrate nAChRs is unknown, there is clear evidence for the existence of distinct neonicotinoid binding sites in native insect preparations, which reflects the predicted wide repertoire of nAChRs and differing pharmacology within this insecticide class. The spinosyns are principally used to control chewing pests such as Lepidoptera, whilst nereistoxin analogues are used on pests of rice and vegetables through contact and systemic action, the pharmacology of both these insecticides is unique and different to that of the neonicotinoids.

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“…[16,17] The insecticidal mechanism of sulfoxaflor is reliant on the agonistic action towards the insect nicotinic acetylcholine receptor (nAChR). [18][19][20][21] The effects of sulfoxaflor on the insects include excitatory symptoms, such as tremors, followed by paralysis and mortality, thereby suggesting that the molecule acts on the insect nervous system. [19] Recent studies have reported that the sulfoximine structure can improve the insecticidal activities of anthranilic diamides.…”

Section: Introductionmentioning

confidence: 99%

Novel Anthranilic Diamide Insecticides: Design, Synthesis, and Insecticidal Evaluation

Hua¹,

Mao²,

Fan³

et al. 2014

Aust. J. Chem.

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Three series of new anthranilic diamide derivatives containing sulfide, N-cyanomethylsulfilimine, and N-cyanomethylsulfoximine groups were designed and synthesized by coupling the active substructures of anthranilic diamides and sulfoxaflor. The structures of the synthesized compounds were confirmed by infrared spectroscopy, 1 H and 13 C NMR, and elemental analysis. Several unique structural characteristics were revealed via the crystal structure analysis of compoundBioassay results indicated that most of the synthesized compounds showed superior insecticidal activities against Mythimna separata and Plutella xylostella when compared with the positive control cyantraniliprole. In particular, N- (2-(2-methyl-2-(N-cyanomethylsulfideimino)propylcarbamoyl)-4-chloro-6-methylphenyl)-3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide 17e showed excellent insecticidal activity against Mythimna separata, with a mortality rate of 100 % at a concentration of 1 mg mL À1 . These results indicated that sulfide, N-cyanomethylsulfilimine, and N-cyanomethylsulfoximine moieties, as important active substructures, could improve or maintain the activity of the anthranilic diamide and promote novel pesticide development.

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Investigating the mode of action of sulfoxaflor: a fourth‐generation neonicotinoid

Cited by 112 publications

References 38 publications

Chance and design in proinsecticide discovery

Chance and design in proinsecticide discovery

The invertebrate pharmacology of insecticides acting at nicotinic acetylcholine receptors

Novel Anthranilic Diamide Insecticides: Design, Synthesis, and Insecticidal Evaluation

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