Design, Synthesis, Antibacterial Activity, and Antivirulence Factor of Novel 1,2,4-Thiadiazole Derivatives Containing an Amide Moiety

To develop antibacterial agents with novel mechanisms of action, a series of novel 1,2,4-thiadiazole derivatives containing amide structures were designed and synthesized. The antibacterial activities of derivatives against <i>Xanthomonas oryzae</i> pv. <i>oryzicola</i> (<i>Xoc</i>), <i>Xanthomonas oryzae</i> pv. <i>oryzae</i> (<i>Xoo</i>), and <i>Pseudomonas syringae</i> pv. <i>actinidiae</i> (<i>Psa</i>) were evaluated, and all derivatives were exhibited excellent antibacterial activities. Among them, compound <b>Z4</b> demonstrated significant antibacterial activities against <i>Xoo</i>, <i>Xoc</i>, and <i>Psa</i>, with EC₅₀ values of 0.32, 0.43, and 11.06 mg/L, respectively. Compound <b>Z4</b> exhibited a protective activity of 49.42% and a curative activity of 44.93% against rice bacterial leaf blight. In addition, compound <b>Z4</b> could inhibit pathogenic bacteria by inhibiting a variety of virulence factors (exopolysaccharides, biofilms, motility, and extracellular enzymes). Compound <b>Z4</b> stimulated the biochemical process of rice self-defense signaling by affecting cell transcription and translation and induced rice self-defense genes and controlled hypersensitivity reactions to resist pathogen infection.