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 10ae , known as ethyl 3-((6-fluoro-5-(6-oxo-4-(trifluoromethyl)pyridazin-1(6 H )-yl)benzo[ d ]thiazol-2-yl)thio)propanoate, emerged as a standout performer. It exhibited robust activity against Nicotiana tabacum PPO ( Nt PPO) with an inhibition constant ( K i ) value of 0.0338 μM. Concurrently, we employed molecular simulations to obtain further insight into the binding mechanism with Nt PPO. Additionally, another compound, namely, ethyl 2-((6-fluoro-5-(5-methyl-6-oxo-4-(trifluoromethyl)pyridazin-1(6 H )-yl)benzo[ d ]thiazol-2-yl)thio)propanoate ( 10bh ), demonstrated broad-spectrum and highly effective herbicidal properties against all six tested weeds ( Leaf mustard , Chickweed , Chenopodium serotinum , Alopecurus aequalis , Poa annua , and Polypogon fugax ) at the dosage of 150 g a.i./ha through postemergence application in a greenhouse. This work identified a novel lead compound ( 10bh ) that showed good activity in vitro and excellent herbicidal activity in vivo and had promising prospects as a new PPO-inhibiting herbicide lead.