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.