Design, Synthesis, and Biological Evaluation of Pyridazinone-Containing Derivatives As Novel Protoporphyrinogen IX Oxidase Inhibitor
Bai-Feng Zheng, Yang Zuo, Wenyi Yang, Hui Liu, Qiong‐You Wu, Guang‐Fu Yang
Abstract
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.