Abstract：
Protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) is one of the most important targets for the discovery of green herbicides. In order to find novel PPO inhibitors with a higher herbicidal activity, a series of novel N-phenyltriazinone derivatives containing oxime ether and oxime ester groups were designed and synthesized based on the strategy of pharmacophore and scaffold hopping. Bioassay results revealed that some compounds showed herbicidal activities; especially, compound B16 exhibited broad-spectrum and excellent 100% herbicidal effects to Echinochloa crusgalli, Digitaria sanguinalis, Setaria faberii, Abutilon juncea, Amaranthus retroflexus, and Portulaca oleracea at a concentration of 37.5 g a.i./ha, which were comparable to trifludimoxazin. Nicotiana tabacum PPO (NtPPO) enzyme inhibitory assay indicated that B16 showed an excellent enzyme inhibitory activity with a value of 32.14 nM, which was similar to that of trifludimoxazin (31.33 nM). Meanwhile, compound B16 revealed more safety for crops (rice, maize, wheat, peanut, soybean, and cotton) than trifludimoxazin at a dose of 150 g a.i./ha. Moreover, molecular docking and molecular dynamics simulation further showed that B16 has a very strong and stable binding to NtPPO. It indicated that B16 can be used as a potential PPO inhibitor and herbicide candidate for application in the field.
摘要：
原卟啉原IX氧化酶（PPO，EC1.3.3.4）是发现绿色除草剂的最重要目标之一。为了寻找具有较高除草活性的新型PPO抑制剂,基于药效团和支架跳跃策略，设计并合成了一系列含有肟醚和肟酯基团的新型N-苯基三嗪酮衍生物。生物测定结果表明，一些化合物具有除草活性；特别是，化合物B16对黄连具有广谱和优异的100%除草效果，血Digitariasanguinalis,SetariaFaberii,Abutilonjuncea，Amaranthus回曲，和马齿莲，浓度为37.5ga.i./ha，与曲氟地沙嗪相当。烟草PPO（NtPPO）酶抑制试验表明，B16表现出优异的酶抑制活性，值为32.14nM，这与三氟西沙嗪(31.33nM)相似。同时,化合物B16对作物(水稻，玉米,小麦,花生,大豆,和棉花）的剂量为150ga.i./ha的三氟西沙嗪。此外，分子对接和分子动力学模拟进一步表明B16与NtPPO具有很强的稳定结合作用。这表明B16可以作为一种潜在的PPO抑制剂和除草剂候选物应用于该领域。
