Identification of imidazo[1,2-a]pyridine skeleton as new bactericidal candidates: structural innovation and...

Given the escalating challenges posed by antimicrobial resistance in phytobacterial infections, which are exacerbated by the suboptimal efficacy of existing bactericides, limited curative options, and mounting environmental concerns, there is a pressing need to develop innovative bactericidal agents with novel molecular architectures and distinctive modes of action.

To identify novel molecular scaffolds for bactericide development, we systematically devised a wide series of imidazo[1,2-a]pyridine derivatives incorporating benzylpiperazinyl moieties, followed by evaluating their antibacterial activities. Bioassay results manifested that compound C₁₉ exhibited remarkable antibacterial efficacy against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac), with EC₅₀ values of 2.16 μg mL^-1 and 4.64 μg mL^-1, respectively. Transcriptomic analysis initially revealed that compound C₁₉ involved significant downregulation of genes associated with biofilm, type III secretion system (T3SS), and flagella assembly. Subsequent multiple validations via biofilm formation assays, bacterial ultrastructure analysis, motility assays, virulence evaluation, and hypersensitive response (HR) assays, collectively indicated that compound C₁₉ both inhibited biofilm formation and suppressed swimming ability while reducing the expression of hrp family genes in T3SS, ultimately attenuating Xoo pathogenicity. Notably, Pot experiment demonstrated that compound C₁₉ exhibited superior control efficacy (protective activity: 42.74%; curative activity: 44.14%), surpassing commercial BT and TC.

Given its excellent antibacterial potency and the mechanism of action elucidated through transcriptome analysis and ample biochemical assays, compound C₁₉ represented a promising candidate for developing novel bactericides via targeting bacterial virulence to combat refractory plant bacterial diseases. © 2025 Society of Chemical Industry.