Synthesis, anti‐ Xanthomonas oryzae pv. oryzae activity and antibacterial mechanism of indole‐3‐substituted‐1,3,4‐oxadiazole derivative

BACKGROUND: Bacterial leaf blight (BLB) caused by Xanthomonas oryzae pv. oryzae (Xoo) seriously endangers global rice production. It is urgent to explore efficient and low-toxic antibacterial candidates for sustainable bacterial blight management. RESULTS: ], 19-32-fold more potent than thiodiazole copper, with (respectively) 72.35% and 75.68% therapeutic, and 72.64% and 72.33% protective efficacy on rice. Mechanistic studies demonstrated concurrent suppression of EPS/biofilm formation, induction of reactive oxygen species (ROS-mediated apoptosis in Xoo, and downregulation of virulence and accC-associated genes - validated by RNA-seq. Molecular dynamics (MD) simulations revealed stable polar anchoring of T8 to accC-Arg381 versus electrostatic repulsion experienced by T2 at accC-Lys250/Arg23. Biosafety tests on HEK293T cells and silkworms verified their low toxicity. CONCLUSION: T2 and T8 were identified as high-efficiency and biosafe anti-Xoo lead compounds. This study provides valuable candidate molecules and a theoretical basis for the development of novel green bactericides against rice bacterial blight. © 2026 Society of Chemical Industry.