Discovery of Novel Anthranilic Diamide Derivatives Bearing Sulfoximine Group as Potent Insecticide Candidates

The fall armyworm,Spodoptera frugiperda(S.frugiperda),represents the most resistant insect species and poses serious threat to grain yield.Chlorantraniliprole(CHL),which targets the ryanodine receptors(RyRs)in insects,has demonstrated the efficacy in controlling S.frugiperda.Nevertheless,this has led to emerging resistance in several countries.To counter this resistance,a viable approach involves the development of novel compounds that bind against RyRs via distinct binding sites or modes.In this study,a series of 22 novel anthranilic diamide derivatives was designed and synthesized,and their insecticidal activities were evaluated.Most of these derivatives showed moderate to good insecticidal activity against S.frugiperda and Mythimna separata.Time-lapse fluorescence measurements of endoplasmic reticulum luminal calcium revealed that most derivatives elicited cellular responses similar as CHL when assessed on HEK293 cells expressing S.frugiperda ryanodine receptors(SfRyRs).The mode of action of compound 13a was studied and verified on the isolated neurons by calcium imaging technique.Finally,molecular docking analysis was employed to predict the binding mechanism of compound 13a against SfRyRs.Overall,these novel diamide derivatives hold promise as a valuable resource for guiding the future design of insecticidal compounds targeting RyRs.

Targeted Synthesis of Anthranilic Diamides Insecticides Containing Trifluoroethoxyl Phenylpyrazole

A series of novel anthranilic diamides analogues(9a-9t)containing trifluoroethoxyl pyrazole moiety was designed and synthesized and their insecticidal bioactivities against Mythimna separata(Walker,M.separata)and Plutellaxylostella(P.xylostella)were evaluated.The structures of the title compounds were confirmed by^(1)H NMR,^(13)C NMR and HRMS.Preliminary insecticidal activities showed that some of the title compounds possessed good to excellent bioactivities towards M.separata and P.xylostella.Compounds 9c and 9t exhibited 100%mortality rate against M.separate at 0.2 mg/L.For the P.xylostella,the synthesized compounds(9c-9e,9i and 9o)showed 70%,80%,75%,65%and 60%insecticidal activities at 1×10^(−6)mg/L,respectively,higher than that of chlorantraniliprole(0).Based on excellent insecticidal activities,the mode of the action was tested by the calcium-imaging technique,the results of which demonstrated that the novel compounds shared the same target with chlorantraniliprole.The binding pose of the most active compound 9t in RyRs of P.xylostella was predicted by molecular docking,which showed that compound 9t interacted with the residues Glu140(A)and His147(A)via hydrogen bond.