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

Abstract

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.

Keywords

Anthranilic diamide derivative / Sulfoximine / Spodoptera frugiperda / Mode of action / Molecular docking

References

[[1]] Lu Q, Xie H J, Qu M B, Liu T, Yang Q. . J. Agric. Food Chem., 2023, 71: 5944

[[2]] Du J, Fu Y J. . Biochem. Biophys. Res. Commun., 2023, 670: 19,

[[3]] Gutiérrez-Moreno R, Mota-Sanchez D, Blanco C A, Whalon M E, Terán-Santofimio H, Rodriguez-Maciel J C, DiFonzo C. . J. Econ. Entomol., 2019, 112: 792,

[[4]] Lahm G P, Selby T P, Freudenberger J H, Stevenson T M, Myers B J, Seburyamo G, Smith B K, Flexner L, Clark C E, Cordova D. . Bioorg. Med. Chem. Lett., 2005, 15: 4898,

[[5]] Clark D A, Lahm G P, Smith B K, Barry J D, Clagg D G. . Bioorg. Med. Chem., 2008, 16: 3163,

[[6]] Du S, Hu X P. . J. Agric. Food Chem., 2023, 71: 3620,

[[7]] Anderson B, Fernando E P, Antonio R N, Ingrid S K, Ewerton C L, Fernando S A, Rubens H K, José B M, Celso O. . Pest Manag. Sci., 2019, 75: 2682,

[[8]] Lv S L, Shi Y, Zhang J C, Liang P, Zhang L, Gao X W. . Insect Sci., 2021, 28: 639,

[[9]] Liu J B, Li F Y, Dong J Y, Li Y X, Zhang X L, Wang Y H, Xiong L X, Li Z M. . Bioorg. Med. Chem., 2018, 26: 3541,

[[10]] Liu J B, Li F Y, Li Y X, Zhang X L, Hua X W, Xiong L X, Li Z M. . Pest Manag. Sci., 2019, 75: 1034,

[[11]] Li F Y, Wang Y H, Liu J B, Li Y X, Li Z M. . Bioorg. Med. Chem., 2019, 27: 769,

[[12]] Liu J B, Li F Y, Hao Z S, Wang Y H, Hua X W, Li Y X, Li Z M. . Bioorg. Med. Chem., 2020, 28: 115829,

[[13]] Li H G, Zhao Y Y, Sun P W, Gao L, Xiong L X, Yang N, Zhou S, Li Y X, Li Z M. . Chem. Res. Chinese Universities, 2021, 37: 655,

[[14]] Zhang Z, Sun P W, Zhao J H, Zhang H Y, Wang X Y, Li L S, Xiong L X, Yang N, Li Y X, Yuchi Z G, Li Z M. . Pest Manag. Sci., 2022, 78: 2022,

[[15]] Jeanguenat A, Lamberth C. . Pest Manag. Sci., 2023, 79: 2647,

[[16]] Devendar P, Yang G F. . Top. Curr. Chem., 2017, 375: 82,

[[17]] Misani F, Fair T W, Reiner L. . J. Am. Chem. Soc., 1951, 73: 459,

[[18]] Foote K. M., Nissink M. J. W., Turner P., Morpholino Pyrimidines and Their Use in Therapy, AstraZeneca Patent WO 2011/154737 A1, 2011

[[19]] Siemeister G, Lücking U, Wengner A M, Lienau P, Steinke W, Schatz C, Mumberg D, Ziegelbauer K. . Mol. Cancer Ther., 2012, 11: 2265,

[[20]] Lücking U. . Angew. Chem. Int. Ed., 2013, 52: 9399,

[[21]] Chen X., Feng J., Fu F., Meng Z., Shi Z., Wang P., Sulfoxaflor Pesticidal Preparation Used for Preventing and Controlling Bemisia Tabaci, Comprises Sulfoxaflor and Additive, in Weight Ratio of Preset Range, and Is in Form of Microemulsion, Aqueous Emulsion, or Suspension, CN103734167-A, 2014

[[22]] Jeanguenat A., O’Sullivan A. C., New Phthalamide Derivatives Useful for: Controlling Pests, and Insects or Representatives of the Order e.g., Acarina and Lepidoptera; Protecting Plant propagation Material from the Attack by Pests, WO 2006032462, 2006

[[23]] Lim H J, Lee W H, Park S J. . Molecules, 2019, 24: 3451, pmcid: 6804157

[[24]] Wu Y D, Shen J L, Chen J, Lin X W, Li A W. . Plant Prot., 1996, 22: 3

[[25]] Hardke J, Temple J, Leonard B, Jackson R. . Fla. Entomol., 2011, 94: 272,

[[26]] Suzuki J, Kanemaru K, Ishii K, Ohkura M, Okubo Y, Iino M. . Nat. Commun., 2014, 5: 4153,

[[27]] Takahashi A, Camacho P, Lechleiter J D, Herman B. . Physiol. Rev., 1999, 79: 1089,

[[28]] Schrödinger Release 2017-1: MacroModel, Schrödinger, LLC: New York, NY, 2017

[[29]] Ma R F, Omid H G, Ma D, Jiang H, Lin L Y, Yao L, Samurkas A, Li Y X, Wang Y W, Cao P, Wu S, Zhang Y, Murayama T, Moussian B, Petegem F V, Yuchi Z G. . Nat. Chem. Biol., 2020, 16: 1246,

[[30]] Schrödinger Release 2017-1: Epik, Schrödinger, LLC: New York, NY, 2017

[[31]] Schrödinger Release 2017-1: Induced Fit Docking Protocol, Schrödinger, LLC: New York, NY, 2017

[[32]] Francesco F, Giovanni G, Francesco R. . Tetrahedron Lett., 1999, 40: 2605,

[[33]] Wang L H, Ai M, Yu J W, Jin L L, Wang C Y, Liu Z H, Shu X H, Tang Z Y, Liu K X, Luo H, Guan W S, Sun X L, Ma X L. . Eur. J. Med. Chem., 2019, 172: 154,

[[34]] Cecile P, Philippe C, Pierre D, Sabine D, Michel G, Frederic G, Thierry K, Patrick P, Nathalie V H, Marc V T. . Bioorg. Med. Chem. Lett., 2007, 17: 4228,

[[35]] Xie Y T, Zhou B Y, Zhou S, Zhou S, Wei W, Liu J B, Zhan Y Z, Cheng D D, Chen M G, Li Y X, Wang B L, Xue X S, Li Z M. . ChemistrySelect, 2017, 2: 1620,

[[36]] Wang B. L., Li Z. M., Zhang Y., Pyrazole CarboxAmide Derivative Containing Substituted Sulfimide Acyl Aryl, and Preparing Method and Application Thereof, CN111170988 A, 2020

[[37]] Cordova D, Benner E A, Sacher M D, Rauh J J, Sopa J S, Lahm G P, Selby T P, Stevenson T M, Flexner L, Gutteridge S, Rhoades D F, Wu L, Smith R M, Tao Y. . Pestic. Biochem. Phys., 2006, 84: 196,