Design, Synthesis, and Biological Evaluation of Pyridazinone-Containing Derivatives As Novel Protoporphyrinogen IX Oxidase Inhibitor.

Protoporphyrinogen IX oxidase (PPO, E.C. 1.3.3.4) plays a pivotal role in chlorophyll biosynthesis in plants, making it a prime target for herbicide development. In this study, we conducted an investigation aimed at discovering PPO-inhibiting herbicides. Through this endeavor, we successfully identified a series of novel compounds based on the pyridazinone scaffold. Following structural optimization and biological assessment, compound , known as ethyl 3-((6-fluoro-5-(6-oxo-4-(trifluoromethyl)pyridazin-1(6)-yl)benzo[]thiazol-2-yl)thio)propanoate, emerged as a standout performer. It exhibited robust activity against PPO (PPO) with an inhibition constant () value of 0.0338 μM. Concurrently, we employed molecular simulations to obtain further insight into the binding mechanism with PPO. Additionally, another compound, namely, ethyl 2-((6-fluoro-5-(5-methyl-6-oxo-4-(trifluoromethyl)pyridazin-1(6)-yl)benzo[]thiazol-2-yl)thio)propanoate (), demonstrated broad-spectrum and highly effective herbicidal properties against all six tested weeds (, , , , , and ) at the dosage of 150 g a.i./ha through postemergence application in a greenhouse. This work identified a novel lead compound () that showed good activity in vitro and excellent herbicidal activity in vivo and had promising prospects as a new PPO-inhibiting herbicide lead.