Abstract：
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 Nicotiana tobacco PPO (NtPPO) and herbicidal activity were evaluated. Among them, compounds B11 (Ki = 9.05 nM) and B20 (Ki = 10.23 nM) showed significantly better inhibitory activity against NtPPO than that against flumiclorac-pentyl (Ki = 46.02 nM). Meanwhile, compounds A20 and B20 were 100% effective against three weeds (Abutilon theophrasti, Amaranthus retroflexus, and Portulaca oleracea) at 37.5 g a.i./ha. It was worth observing that compound B11 was more than 90% effective against three weeds (Abutilon theophrasti, Amaranthus retroflexus, and Portulaca oleracea) 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 B11 could stably bind to NtPPO 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 B11 could be used as a new PPO inhibitor, and it could help control weeds in agricultural production.
摘要：
原卟啉原氧化酶(PPO，EC1.3.3.4)在新抑制剂的开发中具有很高的地位。开发新型高效PPO抑制剂,活性亚结构连接和生物等位取代策略用于设计和合成含有恶二唑/噻二唑部分的新型四氢邻苯二甲酰亚胺衍生物，并评价了其对烟草PPO（NtPPO）的抑制作用和除草活性。其中,化合物B11(Ki=9.05nM)和B20(Ki=10.23nM)对NtPPO的抑制活性明显优于对氟氯戊基(Ki=46.02nM)。同时,化合物A20和B20对三种杂草有100%的有效(Abutilontheophrasti，Amaranthus回曲，和马齿莲）37.5ga.i./ha。值得观察的是，化合物B11对三种杂草的有效性超过90％（Abutilontheophrasti，Amaranthus回曲，和马齿莲）18.75和9.375ga.i./ha。对大米也更安全，玉米,和小麦比氟氯戊基在150克a.i./公顷。此外,分子对接结果表明，化合物B11可以稳定地结合NtPPO，并且与Arg98（2.9µ）的氢键强于氟氯戊基（3.2µ）。这项研究表明，化合物B11可以作为一种新的PPO抑制剂，它可以帮助控制农业生产中的杂草。
