Design, Synthesis and Herbicidal Activity of 1,2,4-Oxadiazole Compounds as Novel Light-Dependent Protochlorophyllide Oxidoreductase Inhibitors

Light-dependent protochlorophyllide oxidoreductase (LPOR, E.C.1.3.1.33) plays a crucial role in the biosynthesis of chlorophyll in plants. Therefore, inactivating LPOR can hinder the production of chlorophyll to achieve the effect of weed control. In this research, utilizing an active substructure splicing method, 20 new 1,2,4-oxadiazole compounds targeting LPOR were synthesized. Among them, compounds <b>5j</b>, <b>5k</b> and <b>5q</b> exhibited superior inhibitory efficacy in greenhouse herbicidal trials. In vitro enzyme activity assays indicated that <b>5q</b> significantly inhibited <i>Arabidopsis thaliana</i> LPOR (<i>At</i>LPOR), with an IC₅₀ value of 17.63 μM. Furthermore, compound <b>5q</b> exhibited superior crop safety and holds potential application prospects for weed management in cotton. Molecular docking and dynamic simulations were employed to elucidate the binding mode and molecular mechanism of <b>5q</b> with <i>At</i>LPOR. These experimental and theoretical results indicate that <b>5q</b> is a promising candidate for the development of novel herbicides targeting LPOR.