Discovery of Pyrimidinedione Derivatives as Potential Herbicides: Design, Synthesis, and Evaluation of Herbicidal Activity

  • J Agric Food Chem. 2025 Sep 3;73(35):21880-21888. doi: 10.1021/acs.jafc.5c02641.
Hongyan Pei  1  2 ,  Jialin Ye  2 ,  Dongdong Liu  2  3 ,  Yixing Gao  1  2  4 ,  Jing Zhang  2  4 ,  Lixin Zhang  1  2  3  4
Affiliations
  • 1. School of Materials Science and Engineering, Shenyang University of Technology, Shenyang 110870, Liaoning, China.
  • 2. Institute of Functional Molecules, Shenyang University of Chemical Technology, Shenyang 110142, Liaoning, China.
  • 3. School of Chemical Engineering, University of Science and Technology Liaoning, Anshan 114051, Liaoning, China.
  • 4. Metisa Biotechnology Co., Ltd., Nanning 530000, China.
PMID: 40828669 DOI: 10.1021/acs.jafc.5c02641
Abstract

Weeds significantly impact crop yields, and pyrimidinedione herbicides remain essential for weed control. Protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4), a key enzyme whose inhibition disrupts chloroplast formation in Plants, serves as a critical target for developing eco-friendly herbicides. To discover novel, potent, and environmentally benign herbicidal agents, we designed and synthesized a series of sulfonamide-containing pyrimidinedione derivatives via scaffold hopping. Postemergence tests revealed that most compounds exhibited strong herbicidal activity against broadleaf weeds. Notably, compound 6q achieved 100% efficacy against Zinnia elegans (ZE) and Abutilon theophrasti (AT) at 9.375 g a.i./ha, comparable to saflufenacil. Electrostatic potential (ESP) analysis indicated a correlation between the charge distribution and herbicidal activity. Molecular docking demonstrated that 6q forms a hydrogen bond with Arg98 and π-π stacking with Phe392. This study provides the theoretical basis for the discovery of pyrimidinedione derivatives as potential herbicides.

Keywords
DFT calculation; berbicide; molecular docking; pyrimidinedione; scaffold hopping; sulfonamide group.
Products