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.

绿色杀虫剂分子靶标研究的难点与挑战

绿色杀虫剂是保证国家粮食安全的战略性物资。随着全球农业的绿色化和可持续化的发展进程,靶标导向并且对人畜和非靶标生物安全的新农药创制已成为该领域研究的必然趋势和制高点,其核心基础是农药分子靶标的创新。一方面,全球超过80%杀虫剂是基于4个晶体结构明确的分子靶标设计的,这一局面导致极高的害虫抗药性;另一方面,分子生物学功能验证技术揭示出大量害虫生长发育所必需的关键基因,如何利用这些资源开发创新的分子靶标是我们面临的挑战。在靶标研究中,获得原子水平的靶标结构信息以及靶标分子与活性小分子之间的相互作用信息是难点。在此背景下,我国有必要尽快建立针对害虫特有而人畜没有的分子靶标挖掘与利用的技术体系,推进安全高效绿色杀虫剂的原始创新。