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

Abstract 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 Herein, 25 indole‐3‐substituted 1,3,4‐oxadiazole derivatives were rationally synthesized. T2 and T8 showed prominent anti‐ Xoo activity [median effective concentration (EC 50 ) = 2.63 and 1.81 μg mL −1 ], 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.