BACKGROUND: Herbicides based on protoporphyrinogen IX oxidase (PPO
EC 1.3.3.4) are widely used for weeding control in agricultural fields to safeguard food security. PPO herbicides, because of their low dosage, rapid action on weeds, slow accumulation in the environment and low toxicity to mammals, have become an important field of research in the development of new herbicides. This study presents a novel molecular scaffold with remarkably potent herbicidal activity. RESULTS: A series of novel oxime ether derivatives containing 1,5-dimethyl-6-thioxo-1,3,5-triazinane-2,4-dione 6a-6z were designed and synthesized based on bioisosterism and substructure splicing, and characterized by CONCLUSION: Through bioisosterism and substructure splicing, we successfully developed compound 6r as lead compound exhibiting herbicidal activity, with no harm to rice and honeybees. Further development of herbicides based on this scaffold is warranted. © 2025 Society of Chemical Industry.