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 (EC50) = 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.