Insect growth regulators (IGRs) are important green insecticides that disrupt normal growth and development in insects to reduce the harm caused by pests to crops. The ecdysone receptor (EcR) and three chitinases OfChtI, OfChtII, and OfChi-h are closely associated with the molting stage of insects. Thus, they are considered promising targets for the development of novel insecticides such as IGRs. Our previous work identified a dual-target compound 6j, which could act simultaneously on both EcR and OfChtI. In the present study, 6j was first found to have inhibitory activities against OfChtII and OfChi-h, too. Subsequently, taking 6j as a lead compound, 19 novel acetamido derivatives were rationally designed and synthesized by introducing an acetamido moiety into the amide bridge based on the flexibility of the binding cavities of 6j with EcR and three chitinases. Then, their insecticidal activities against Plutella xylostella (P. xylostella), Ostrinia furnacalis (O. furnacalis), and Spodoptera frugiperda (S. frugiperda) were carried out. The bioassay results revealed that most of these acetamido derivatives possessed moderate to good larvicidal activities against three lepidopteran pests. Especially, compound I-17 displayed excellent insecticidal activities against P. xylostella (LC₅₀, 93.32 mg/L), O. furnacalis (LC₅₀, 114.79 mg/L), and S. frugiperda (86.1% mortality at 500 mg/L), significantly better than that of 6j. In addition, further protein validation and molecular docking demonstrated that I-17 could act simultaneously on EcR (17.7% binding activity at 8 mg/L), OfChtI (69.2% inhibitory rate at 50 μM), OfChtII (71.5% inhibitory rate at 50 μM), and OfChi-h (73.9% inhibitory rate at 50 μM), indicating that I-17 is a potential lead candidate for novel multitarget IGRs. This work provides a promising starting point for the development of novel types of IGRs as pest management agents.

中文翻译：

---

一种潜在的多靶点昆虫生长调节剂候选物：含有六环吡唑甲酰胺的新型乙酰胺衍生物的设计、合成和生物活性

昆虫生长调节剂（IGRs）是重要的绿色杀虫剂，通过扰乱昆虫的正常生长发育来减少害虫对农作物的危害。蜕皮激素受体(EcR)和三种几丁质酶ChtI、Of ChtII和Of Chi-h与昆虫的蜕皮阶段密切相关。因此，它们被认为是开发 IGR 等新型杀虫剂的有希望的目标。我们之前的工作确定了一种双靶点化合物6j，它可以同时作用于 EcR 和Of ChtI。在本研究中，首次发现6j对Of ChtII 和Of Chi-h 也具有抑制活性。随后，以6j为先导化合物，利用6j与EcR和三种几丁质酶结合空腔的灵活性，通过在酰胺桥上引入乙酰氨基部分，合理设计合成了19种新型乙酰氨基衍生物。然后，开展了它们对小菜蛾（P. xylostella）、亚洲玉米螟（O.furnacalis）和草地贪夜蛾（S. frugiperda ）的杀虫活性。生物测定结果表明，大多数乙酰氨基衍生物对三种鳞翅目害虫具有中等至良好的杀幼虫活性。尤其是，化合物I-17对小菜蛾(LC ₅₀， 93.32 mg/L)、亚洲稻蛾(LC ₅₀， 114.79 mg/L) 和草地贪夜蛾(500 mg/L 时死亡率为 86.1%)表现出优异的杀虫活性。 ），明显优于6j。此外，进一步的蛋白质验证和分子对接表明，I-17可以同时作用于 EcR（8 mg/L 时结合活性为 17.7%）、ChtI（50 μM 时抑制率为 69.2%）、ChtII（抑制率为 71.5%） 50 μM）和Chi -h（50 μM 抑制率为 73.9%），表明I-17是新型多靶点 IGR 的潜在先导候选物。这项工作为开发新型 IGR 作为害虫防治剂提供了一个有希望的起点。