Abstract：
4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27; HPPD) is one of the important target enzymes in the development of herbicides. To discover novel HPPD inhibitors with unique molecular, 39 cyclohexanedione derivations containing pyrazole and pyridine groups were designed and synthesized. The preliminary herbicidal activity test results showed that some compounds had obvious inhibitory effects on monocotyledon and dicotyledonous weeds. The herbicidal spectrums of the highly active compounds were further determined, and the compound G31 exhibited the best inhibitory rate over 90% against Plantago depressa Willd and Capsella bursa-pastoris at the dosages of 75.0 and 37.5 g ai/ha, which is comparable to the control herbicide mesotrione. Moreover, compound G31 showed excellent crop safety, with less than or equal to 10% injury rates to corn, sorghum, soybean and cotton at a dosage of 225 g ai/ha. Molecular docking and molecular dynamics simulation analysis revealed that the compound G31 could stably bind to Arabidopsis thaliana HPPD (AtHPPD). This study indicated that the compound G31 could be used as a lead molecular structure for the development of novel HPPD inhibitors, which provided an idea for the design of new herbicides with unique molecular scaffold.
摘要：
4-羟基苯基丙酮酸双加氧酶（EC1.13.11.27；HPPD）是除草剂开发中的重要目标酶之一。为了发现具有独特分子的新型HPPD抑制剂，设计并合成了39种含有吡唑和吡啶基的环己二酮衍生物。初步除草活性试验结果表明,部分化合物对单子叶和双子叶杂草均有明显的抑制作用。进一步确定了高活性化合物的除草光谱，在75.0和37.5gai/ha的剂量下，化合物G31对PlantagodepressaWilld和Capsella囊-pastoris的最佳抑制率超过90％，与对照除草剂甲基磺草酮相当。此外，化合物G31表现出优异的作物安全性，对玉米的伤害率小于或等于10%，高粱,大豆和棉花的用量为225克ai/公顷。分子对接和分子动力学模拟分析表明,化合物G31能够与拟南芥HPPD(AtHPPD)稳定结合。这项研究表明，化合物G31可以作为开发新型HPPD抑制剂的先导分子结构，为具有独特分子支架的新型除草剂的设计提供了思路。
