Design, Synthesis, and Antibacterial Activity of Novel\nSulfone Derivatives Containing a 1,2,4-Triazolo[4,3‑<i>a</i>]Pyridine Moiety

To\ndevelop antibacterial agents with a novel mechanism of action,\na series of sulfone compounds containing a 1,2,4-triazolo[4,3-<i>a</i>]pyridine were designed and synthesized by progressive\nmolecular structure optimization. The antibacterial activities of\nsome derivatives against the four plant pathogens Xanthomonas\noryzae pv. oryzae (<i>Xoo</i>), Xanthomonas oryzae pv. oryzicola (<i>Xoc</i>), Xanthomonas axonopodis pv. citri (<i>Xac</i>), and Pseudomonas syringae\npv. actinidiae (<i>Psa</i>) were evaluated.\nAmong them, compound <b>K3</b> demonstrated significant antibacterial\nactivities against <i>Xoo</i>, <i>Xoc</i>, and <i>Xac</i>, with EC<sub>50</sub> values of 1.5, 1.7, and 4.9 mg/L,\nrespectively. In the greenhouse, compound <b>K3</b> exhibited\na protective activity of 44.49% and a curative activity of 42.51%\nagainst rice bacterial leaf blight, which notably surpassed the traditional\nagents thiodiazole-copper (24.65% and 23.35%) and bismerthiazol (34.69%\nand 30.78%). Furthermore, compound <b>K3</b> can inhibit the\ngrowth of pathogenic bacteria by inhibiting a variety of virulence\nfactors (extracellular polysaccharides, biofilms, and motile and extracellular\nenzymes.). It also induced the production of reactive oxygen species\n(ROS) by the pathogens, leading to their death. Transcriptomic analysis\nrevealed that <b>K3</b> impacts rice biosynthesis, biofilm formation,\nand metabolic processes, enhancing the plant’s self-defense\nbiochemical processes and affecting carbohydrate transport and metabolism\nto resist pathogen invasion. Therefore, the inhibition of virulence\nfactors as a strategy for controlling difficult-to-treat plant bacterial\ndiseases presents a promising approach to the discovery of novel antibacterial\ncandidates.