Synthesis, antibacterial evaluation, and mechanism study of piperazine-bearing oxime ether derivatives

The persistent proliferation of bacterial phytopathogens presents a significant threat to global food security and agricultural sustainability. Among these pathogens, species belonging to the genus Xanthomonas are particularly destructive. Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of bacterial leaf blight in rice, is recognized as one of the most devastating phytopathogens. This strongly indicates that there is an urgent need to create green small-molecule pesticides specifically targeting Xoo.

Herein, we designed and synthesized 20 oxime ether derivatives containing piperazine fragments and systematically evaluated their antibacterial activity. Bioassay results revealed that compound L1 exhibited notable antibacterial efficacy, with a half-maximal effective concentration (EC₅₀) of 7.32 μg mL^-1, significantly outperforming control agents such as thiodiazole-copper (96.90 μg mL^-1) and bismerthiazol (47.20 μg mL^-1). The underlying mechanism of action was investigated using an integrated approach involving molecular docking, morphological observation, three-dimensional quantitative structure-activity relationship modeling, and transcriptome profiling. In addition, the phytotoxicity study results indicate that compound L1 exhibits low toxicity towards plants. The findings of this research provide theoretical insights and experimental guidance for designing novel, potent, and environment-friendly small-molecule antibacterial agents.

Compound L1 represents a promising class of antibacterial agents with potent activity against Xoo. It possesses the dual advantages of high bactericidal efficacy and ecological friendliness, demonstrating great potential to replace traditional agricultural chemicals and promote green prevention and control of plant diseases. © 2026 Society of Chemical Industry.