Design, Synthesis, and Antibacterial Activity of Novel Sulfone Derivatives Containing a 1,2,4-Triazolo[4,3-]Pyridine Moiety.

To develop antibacterial agents with a novel mechanism of action, a series of sulfone compounds containing a 1,2,4-triazolo[4,3-]pyridine were designed and synthesized by progressive molecular structure optimization. The antibacterial activities of some derivatives against the four plant pathogens (), (), (), and () were evaluated. Among them, compound demonstrated significant antibacterial activities against , , and , with EC values of 1.5, 1.7, and 4.9 mg/L, respectively. In the greenhouse, compound exhibited a protective activity of 44.49% and a curative activity of 42.51% against rice bacterial leaf blight, which notably surpassed the traditional agents thiodiazole-copper (24.65% and 23.35%) and bismerthiazol (34.69% and 30.78%). Furthermore, compound can inhibit the growth of pathogenic bacteria by inhibiting a variety of virulence factors (extracellular polysaccharides, biofilms, and motile and extracellular enzymes.). It also induced the production of reactive oxygen species (ROS) by the pathogens, leading to their death. Transcriptomic analysis revealed that impacts rice biosynthesis, biofilm formation, and metabolic processes, enhancing the plant's self-defense biochemical processes and affecting carbohydrate transport and metabolism to resist pathogen invasion. Therefore, the inhibition of virulence factors as a strategy for controlling difficult-to-treat plant bacterial diseases presents a promising approach to the discovery of novel antibacterial candidates.