Discovery of Natural Rosin-Based Herbicide Agent to Control <i>Echinochloa crusgalli</i> for Sustainable Weed Management

Natural rosin derivatives offer a promising scaffold for developing low-toxicity herbicides to address environmental concerns triggered by synthetic agrochemicals. In this research, a series of dehydroabietyl-hydrazide-based derivatives (<b>3a</b>-<b>l</b>) were synthesized using dehydroabietic acid as a lead compound. The herbicidal activities of these derivatives were evaluated against <i>Echinochloa crusgalli</i>, <i>Sorghum halepense</i>, <i>Portulaca oleracea</i>, and <i>Amaranthus caudatus</i> L. weeds. The result indicated that <b>3e</b> exhibited broad-spectrum activity, particularly against barnyard grass root growth, with 91.0% inhibition at 100 μg/mL, outperforming the commercial herbicides naptalam (NPA) and glyphosate. Subsequently, the physiological indicators were employed to reveal the mode of action of <b>3e</b>, and the result suggested that <b>3e</b> significantly inhibited peroxidase enzyme activity, reduced the level of growth-promoting hormones, and increased the inhibitory hormone content, ultimately disrupting endogenous hormone homeostasis. Molecular docking demonstrated that <b>3e</b> stably bound to the POD (-7.73 kcal/mol) via synergistic hydrogen bonding and hydrophobic actions. Crop safety assessments showed that <b>3e</b> presented lower toxicity to wheat, corn, rice, and cotton seedlings at a high concentration of 200 g a.i./ha. The biosafety assessment evaluation also suggested that <b>3e</b> showed lower toxicity to zebrafish, with 96 h median lethal concentration values of 33.9 μg/mL. Overall, these findings suggested that <b>3e</b> could serve as a natural herbicide agent for controlling <i>E. crusgalli</i>, offering a sustainable weed management strategy.