To discover protoporphyrinogen oxidase (PPO) inhibitors with robust herbicidal activity and crop safety, three types of substituted 3-(pyridin-2-yl)phenylamino derivatives bearing amide, urea, or thiourea as side chain were designed via structure splicing strategy. Postemergence herbicidal activity assessment of 33 newly prepared compounds revealed that many of our compounds such as 6a, 7b, and 8d exhibited superior herbicidal activities against broadleaf and monocotyledon weeds to commercial acifluorfen. In particular, compound 8d exhibited excellent herbicidal activities and high crop safety at a dosage range of 37.5–150 g ai/ha. PPO inhibitory studies supported our compounds as typical PPO inhibitors. Molecular docking studies revealed that compound 8d provided effective interactions with Nicotiana tabacum PPO (NtPPO) via diverse interaction models, such as π–π stacking and hydrogen bonds. Molecular dynamics (MD) simulation studies and degradation studies were also conducted to gain insight into the inhibitory mechanism. Our study indicates that compound 8d may be a candidate molecule for the development of novel herbicides.

中文翻译：

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取代的 3-(吡啶-2-基)苯氨基衍生物的设计、合成和除草活性

为了发现具有强大除草活性和作物安全性的原卟啉原氧化酶（PPO）抑制剂，通过结构剪接策略设计了三种带有酰胺、脲或硫脲作为侧链的取代3-（吡啶-2-基）苯氨基衍生物。对 33 种新制备的化合物的芽后除草活性评估表明，我们的许多化合物（例如6a、7b和8d ）对阔叶和单子叶杂草的除草活性优于商业三氟羧草醚。特别是，化合物8d在37.5-150 g ai/ha的剂量范围内表现出优异的除草活性和高作物安全性。 PPO 抑制研究支持我们的化合物是典型的 PPO 抑制剂。分子对接研究表明，化合物8d通过多种相互作用模型（例如π-π堆积和氢键）与烟草PPO（Nt PPO）提供有效的相互作用。还进行了分子动力学（MD）模拟研究和降解研究，以深入了解抑制机制。我们的研究表明化合物8d可能是开发新型除草剂的候选分子。