Zhao Kunhong, Zhang Chun, Zhang Meng, Cai Xiaobo, Wang Sheng, Pu Xian, Li Xiangyang
State Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China.
J Agric Food Chem. 2025 Apr 16;73(15):8822-8832. doi: 10.1021/acs.jafc.4c12504. Epub 2025 Apr 3.
In this study, a series of aminophosphoric acid derivatives were synthesized with 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) as a potential target, and their herbicidal activities were evaluated. At 600 g ai/ha, compounds and exhibited good herbicidal efficacy against (DIGSA) and (SETVI), with inhibition rates of 80% and 90%, and 80% and 95%, respectively. Additionally, both compounds and demonstrated significant enzyme inhibition activity against EPSPS (EPSPS). Expression and purification of EPSPS and EPSPS (EPSPS) proteins followed by microscale thermophoresis (MST) revealed that compounds and had excellent binding affinities for both EPSPS and EPSPS, with dissociation constants () of 0.65 and 1.27 μM, and 0.41 and 0.42 μM, respectively. Isothermal titration calorimetry (ITC) further validated the MST results, which were consistent with expectations. Molecular docking and molecular dynamics (MD) simulations further demonstrated that compounds and formed strong and stable complexes with EPSPS and EPSPS. Moreover, neither compound nor showed specific binding to the EPSPS and EPSPS mutant proteins, confirming that K355 is a key amino acid residue for binding. These findings suggest that compounds and have the potential to act as selective EPSPS inhibitors for the control of six species of grass weeds in crop fields.
