Novel phenoxy-(trifluoromethyl)pyridine-2-pyrrolidinone-based inhibitors of protoporphyrinogen oxidase: Design, synthesis, and herbicidal activity

• Published in: Pesticide biochemistry and physiology 2020-11, Vol.170, p.104684-104684, Article 104684
• Main Authors: Zhao, Li-xia, Hu, Jia-jun, Wang, Zhi-xin, Yin, Min-lei, Zou, Yue-li, Gao, Shuang, Fu, Ying, Ye, Fei
• Format: Article
• Language: English
• Subjects: Herbicidal activity; Herbicide; Molecular docking; Phenoxypyridine-2-pyrrolidinone; PPO
• ISSN: 0048-3575; 1095-9939
• DOI: 10.1016/j.pestbp.2020.104684

As important chemical pesticides, protoporphyrinogen oxidase (PPO, EC 1.3.3.4) herbicides play a vital role in weed management. Herein, in a search for novel PPO herbicides, a series of phenoxypyridine-2-pyrrolidinone derivatives were synthesized and their herbicidal activities were tested. To confirm the structures of the newly synthesized compounds, a colorless single crystal of compound 9d was obtained and crystallographic data collected. PPO inhibition experiments showed that most compounds have PPO inhibitory effects. The half-maximal inhibitory concentration (IC50) of compound 9d and oxyfluorfen were 0.041 mg/L and 0.043 mg/L, respectively, which showed compound 9d was the most potent compound. Compound 9d reduced the Chlorophyll a (Chl a) and Chlorophyll b (Chl b) contents of Abutilon theophrasti (A. theophrasti), to 0.306 and 0.217 mg/g, respectively. Crop selectivity experiments and field trial indicated that compound 9d can potentially be used to develop post-emergence herbicides for weed control in rice, cotton, and peanut. Molecular docking studies showed that both oxyfluorfen and compound 9d can enter the PPO cavity to occupy the active site and compete with the porphyrin to block the chlorophyll synthesis process, affect photosynthesis, and eventually cause weed death. Compound 9d was found to be a promising lead compound for novel herbicide development. [Display omitted] •Novel phenoxy-(trifluoromethyl)pyridine-2-pyrrolidinone skeleton was designed on the basis of active subunit combination and bioisosterism.•Weeds treated with most of the synthesized compounds are necrotic quickly, as these compounds inhibits the participation of PPO in chlorophyll synthesis, which eventually leads to a decrease in chlorophyll content and induces the death of weeds.•Molecular docking simulation and field experiments were conducted on the compound 9d selected in the greenhouse herbicidal activity experiment, chlorophyll content determination, and crop safety experiment, which fully demonstrated that compound 9d has the potential to be developed as a novel PPO herbicide.