Design, synthesis and evaluation of antibacterial activity and mechanism of novel 1-H-indole-3-pyrazolamide derivatives.

Background: Xanthomonas oryzae pv. oryzae (Xoo) is widely acknowledged as a highly destructive bacterial pathogen responsible for bacterial leaf blight (BLB), leading to substantial yield and economic losses in rice cultivation. This study involved the synthesis of 21 novel structural derivatives of 1-H-indole-3-pyrazole-mercaptoacetamide, followed by the assessment of their antibacterial properties.

Results: The majority of the compounds under investigation exhibited inhibitory effects against Xoo. Notably, compound 7 demonstrated superior in vitro inhibitory potency against Xoo with a median effective concentration (EC) value of 2.57 μg mL, outperforming Thiodiazole copper (TC) (63.95 μg mL) and Bismerthiazol (BT) (61.46 μg mL). In glasshouse settings, compound 7 displayed therapeutic efficacy (76.36%) and protective efficacy (88.02%) against rice bacterial leaf blight. Additionally, compound 7 attenuated biofilm formation and extracellular polysaccharide secretion by Xoo, and disrupted the cell membrane, thereby impeding bacterial proliferation. Transcriptomic analysis indicated that differentially expressed genes were predominantly associated with the bacterial type VI secretion system, biotin metabolism, the two-component system, bacterial chemotaxis and flagellar assembly.

Conclusion: This study presents a promising 1-H-indole-3-pyrazole-mercaptoacetamide compound as a novel antibacterial approach. Compound 7 manifests inhibitory actions on Xoo growth by disrupting bacterial flagella assembly, biotin synthesis, the two-component system and the type VI secretion system, showcasing substantial potential for novel antibacterial agent development. © 2025 Society of Chemical Industry.