Design, Synthesis, and Herbicidal Activity of Biaryl-Pyridazinone/Phthalimide Derivatives as Novel Protoporphyrinogen Oxidase Inhibitors

In this study, a series of biaryl-pyridazinone/phthalimide derivatives were designed and synthesized as novel protoporphyrinogen IX oxidase (PPO) inhibitors. Herbicidal activity and crop safety assessments revealed that some compounds exhibited excellent herbicidal activity and crop safety profiles. For instance, at 37.5 g ai/ha, compound 7m inhibited Amaranthus retroflexus (AR), Abutilon theophrasti (AT), Medicago sativa (MS), Echinochloa crus-galli (EC), and Digitaria sanguinalis (DS) with 90% to 100% efficacy, comparable to the commercial herbicide saflufenacil (SAF). Compound 7m still showed effective weed control against the test broadleaf weeds at a lower dose of 9.375 g ai/ha. Additionally, 7m demonstrated excellent safety for wheat and corn at dosages up to 150 g ai/ha. In vitro experiments revealed that the representative compounds exhibited significant inhibitory activity against Arabidopsis thaliana PPO (AtPPO). Molecular docking of Nicotiana tabacum PPO (NtPPO) and 7m showed significant hydrogen bonding, π–π stacking, and π-alkyl interactions between 7m and residues, such as Cys-177, Thr-176, Arg-98, Phe-392, and Leu-372. Furthermore, 7m caused a notable reduction in chlorophyll (Chl) content in weeds. 7m is a promising candidate for the development of novel herbicides.