State Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, China.
J Agric Food Chem. 2024 Aug 7;72(31):17191-17199. doi: 10.1021/acs.jafc.4c01389. Epub 2024 Jul 26.
Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) has a high status in the development of new inhibitors. To develop novel and highly effective PPO inhibitors, active substructure linking and bioisosterism replacement strategies were used to design and synthesize novel tetrahydrophthalimide derivatives containing oxadiazole/thiadiazole moieties, and their inhibitory effects on PPO (PPO) and herbicidal activity were evaluated. Among them, compounds ( = 9.05 nM) and ( = 10.23 nM) showed significantly better inhibitory activity against PPO than that against flumiclorac-pentyl ( = 46.02 nM). Meanwhile, compounds and were 100% effective against three weeds (, , and ) at 37.5 g a.i./ha. It was worth observing that compound was more than 90% effective against three weeds (, , and ) at 18.75 and 9.375 g a.i./ha. It was also safer to rice, maize, and wheat than flumiclorac-pentyl at 150 g a.i./ha. In addition, the molecular docking results showed that compound could stably bind to PPO and it had a stronger hydrogen bond with Arg98 (2.9 Å) than that of flumiclorac-pentyl (3.2 Å). This research suggests that compound could be used as a new PPO inhibitor, and it could help control weeds in agricultural production.
原卟啉原氧化酶（PPO，EC 1.3.3.4）在新型抑制剂的开发中具有重要地位。为了开发新型、高效的 PPO 抑制剂，本研究采用活性亚结构连接和生物等排体替换策略，设计并合成了一系列新型含噁二唑/噻二唑结构的四氢邻苯二甲酰亚胺衍生物，并对其抑制 PPO（PPO）的活性和除草活性进行了评价。其中，化合物 （ = 9.05 nM）和 （ = 10.23 nM）对 PPO 的抑制活性明显优于氟氯草膦-戊基（ = 46.02 nM）。同时，化合物 和 在 37.5 g a.i./ha 剂量下对 3 种杂草（稗草、马唐和反枝苋）的防治效果达到 100%。值得注意的是，化合物 在 18.75 和 9.375 g a.i./ha 剂量下对 3 种杂草（稗草、马唐和反枝苋）的防治效果超过 90%。与氟氯草膦-戊基相比，化合物 在 150 g a.i./ha 剂量下对水稻、玉米和小麦的安全性更高。此外，分子对接结果表明，化合物 能与 PPO 稳定结合，与 Arg98（2.9 Å）形成的氢键比氟氯草膦-戊基（3.2 Å）更强。本研究表明，化合物 可作为一种新型 PPO 抑制剂，有助于控制农业生产中的杂草。
