SummaryOstrinia furnacalis (O. furnacalis) is a commonly occurring agricultural pest that can severely impact corn yield and quality. Therefore, establishing and implementing effective control methods against O. furnacalis are of great significance. Chemical insecticides remain the most effective means to mitigate the damage caused by O. furnacalis. With the increasing resistance of O. furnacalis to insecticides, it is imperative to identify and develop compounds with novel mechanisms of action and high safety. The chitinase OfChi‐h, identified and characterized in O. furnacalis, has been recognized as a potential insecticide target. In this study, a series of azo‐aminopyrimidine analogues were synthesized as OfChi‐h inhibitors employing rational molecular optimization. Among them, compounds 9b, 10a and 10g exhibited Ki values of 23.2, 19.4, and 43.2 nM against OfChi‐h, respectively. Molecular docking studies were carried out to explore the molecular basis for the high efficacy of these compounds and OfChi‐h. In addition, the morphological changes of the cuticle in inhibitor‐treated O. furnacalis larvae were assessed using scanning electron microscopy. Furthermore, the target compounds were assayed in leaf dipping and pot experiments, with compound 10a exhibiting greater insecticidal activity against Plutella xylostella (P. xylostella) and O. furnacalis than diflubenzuron and chlorbenzuron. At the same time, the toxicity of these compounds to natural enemies Trichogramma ostriniae and rats was negligible. The present study demonstrates that the azo‐aminopyrimidine skeleton can be used as a novel, low‐cost scaffold for developing insect chitinolytic enzyme inhibitors, with the potential to be utilized as new environmentally friendly insecticides.

中文翻译：

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偶氮-氨基嘧啶衍生物作为有效的鳞翅目专用几丁质酶抑制剂的合理设计


摘要糠秃鸢尾草（O. furnacalis）是一种常见的农业害虫，可严重影响玉米产量和质量。因此，建立和实施有效的糠秃防治方法具有重要意义。化学杀虫剂仍然是减轻 O. furnacalis 造成的损害的最有效手段。随着 O. furnacalis 对杀虫剂的抗性不断增强，必须识别和开发具有新颖作用机制和高安全性的化合物。在 O. furnacalis 中鉴定和表征的几丁质酶 OfChi-h 已被公认为潜在的杀虫剂靶标。在这项研究中，采用合理的分子优化合成了一系列偶氮-氨基嘧啶类似物作为 OfChi-h 抑制剂。其中，化合物 9b 、 10a 和 10g 对 OfChi-h 的 Ki 值分别为 23.2 、 19.4 和 43.2 nM。进行分子对接研究以探索这些化合物和 OfChi-h 高效性的分子基础。此外，使用扫描电子显微镜评估了抑制剂处理的 O. furnacalis 幼虫角质层的形态变化。此外，在叶浸和盆栽实验中测定了目标化合物，化合物 10a 对 Plutella xylostella （P. xylostella） 和 O. furnacalis 表现出比二氟苯脲和氯苯脲更大的杀虫活性。同时，这些化合物对天敌 Trichogramma ostriniae 和大鼠的毒性可以忽略不计。本研究表明，偶氮-氨基嘧啶骨架可用作开发昆虫几丁质溶解酶抑制剂的新型、低成本支架，并有可能用作新的环保杀虫剂。