Novel Sulfonamide Derivatives Containing the α-Aminophosphonate Backbone: A Biofilm Inhibitor for Preventing and...

The formation of bacterial biofilms enhances pathogen resistance, reducing the efficacy of traditional antibacterial agents. Consequently, developing new and efficient biofilm inhibitors is critical. Herein, a series of sulfonamide derivatives containing α-aminophosphonate fragments were designed, synthesized, and evaluated for antimicrobial activities. In vitro bioassay revealed the superior efficacy of compound A20 (EC₅₀ = 26.6 μg mL^-1) over the commercial bactericide thiodiazole copper (EC₅₀ = 82.5 μg mL^-1) against Xanthomonas axonopodis pv. citri (Xac). Further studies demonstrated that A20 effectively inhibited Xac biofilm formation and reduced multiple virulence factors, including extracellular enzyme activity, motility, and extracellular polysaccharide (EPS) production. These excellent properties are undoubtedly transmitted to in vivo activity, yielding preventive efficacies of 75.32% and 50.28% against citrus bacterial canker at 200 μg mL^-1, surpassing those of thiodiazole copper (57.52% and 43.83%). These findings indicate that inhibiting biofilm formation represents a promising strategy for developing novel antibacterial agents to manage persistent plant bacterial diseases.