In Silico Structure-Guided Optimization and Molecular Simulation Studies of 3-Phenoxy-4-(3-trifluoromethylphenyl)pyridazines as Potent Phytoene Desaturase Inhibitors
Lijun Yang,
Dawei Wang,
Dejun Ma,
Di Zhang,
Nuo Zhou,
Jing Wang,
Han Xu,
Zhen Xi
Affiliations
Lijun Yang
National Pesticide Engineering Research Center, Department of Chemical Biology, State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China
Dawei Wang
National Pesticide Engineering Research Center, Department of Chemical Biology, State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China
Dejun Ma
National Pesticide Engineering Research Center, Department of Chemical Biology, State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China
Di Zhang
National Pesticide Engineering Research Center, Department of Chemical Biology, State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China
Nuo Zhou
National Pesticide Engineering Research Center, Department of Chemical Biology, State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China
Jing Wang
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38, Xueyuan Road, Beijing 100191, China
Han Xu
National Pesticide Engineering Research Center, Department of Chemical Biology, State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China
Zhen Xi
National Pesticide Engineering Research Center, Department of Chemical Biology, State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China
A series of novel 3-phenoxy-4-(3-trifluoromethylphenyl)pyridazines 2–5 were designed, based on the structure of our previous lead compound 1 through the in silico structure-guided optimization approach. The results showed that some of these new compounds showed a good herbicidal activity at the rate of 750 g ai/ha by both pre- and post-emergence applications, especially compound 2a, which displayed a comparable pre-emergence herbicidal activity to diflufenican at 300–750 g ai/ha, and a higher post-emergence herbicidal activity than diflufenican at the rates of 300–750 g ai/ha. Additionally, 2a was safe to wheat by both pre- and post-emergence applications at 300 g ai/ha, showing the compound’s potential for weed control in wheat fields. Our molecular simulation studies revealed the important factors involved in the interaction between 2a and Synechococcus PDS. This work provided a lead compound for weed control in wheat fields.
