Zhang Panxiu, Cao Haifeng, Li Tiansong, Fu Ying
Department of Chemistry, College of Arts and Sciences, Northeast Agricultural University, Harbin 150030, China.
National Soybean Engineering Technology Research Center, Northeast Agricultural University, Harbin 150030, China.
Molecules. 2025 Mar 27;30(7):1491. doi: 10.3390/molecules30071491.
Novel herbicide development is a challenge for weed control. Protoporphyrinogen oxidase (PPO) and -hydroxyphenylpyruvate dioxygenase (HPPD) are two key enzymes involved in plant photosynthesis. The multi virtual screening protocol was adopted to design a common skeleton based on the two target enzymes, and fragment growth of the skeleton was performed. The constructed compounds were searched for structural similarity, and the accuracy of the selected compounds was further verified using the Bayesian model. Finally, eight compounds were obtained, and the binding mode with the target was studied deeply. The obtained compounds interact with the key residues of HPPD and PPO proteins similarly to commercial herbicides, and the stability of binding with proteins is also good. The activity of the screening results was determined by an enzyme activity test in vitro. The herbicidal effect of the compound was studied by phenotypic experiment. The final results showed that Z-4 and Z-7 have the potential to become new dual-target herbicides.
新型除草剂的开发是杂草防治面临的一项挑战。原卟啉原氧化酶（PPO）和对羟基苯丙酮酸双加氧酶（HPPD）是参与植物光合作用的两种关键酶。采用多虚拟筛选方案基于这两种靶标酶设计了一个共同骨架，并对该骨架进行片段生长。对构建的化合物进行结构相似性搜索，并使用贝叶斯模型进一步验证所选化合物的准确性。最终获得了8种化合物，并深入研究了它们与靶标的结合模式。所获得的化合物与HPPD和PPO蛋白的关键残基相互作用，类似于市售除草剂，并且与蛋白结合的稳定性也良好。通过体外酶活性测试确定筛选结果的活性。通过表型实验研究了该化合物的除草效果。最终结果表明，Z-4和Z-7有潜力成为新型双靶标除草剂。
