Natural product scaffold-based bactericide discovery: novel β-carboline derivatives as potent reactive oxygen species inducers for crop disease control

Natural β-carboline alkaloids have emerged as one of the most promising scaffolds in anticancer and fungicidal agent discovery. However, their application in antiphytopathogenic bacteria remains underexplored, primarily due to challenges in synthetic accessibility and insufficiently elucidated mechanisms of action. This gap has created a significant bottleneck in translating these natural products into practical agricultural applications.

Basing on the natural β-carboline (βC) scaffold, 41 synthetic derivatives and six commercialized analogues were obtained to discuss the chemical space on bioactivity against phytopathogenic bacteria. Structure-activity relationship studies revealed that modifications at the C3, C1, and C6 positions of the natural βC scaffold, as well as the number and position of nitrogen atoms in ring C, significantly influenced antibacterial efficacy. Notably, 1-propyl substituted molecule B2 exhibited optimal antibacterial activity with an EC₅₀ value of 1.12 μg mL^-1 against Xanthomonas oryzae pv. oryzae. Pot experiments manifested that B2 achieved excellent in vivo control efficacy against rice bacterial leaf blight with protective and curative activities of 45.47% and 55.51% at 200 μg mL^-1, respectively, outperforming bismerthiazol (38.09% and 37.16%) and thiodiazole-copper (21.40% and 28.47%). Mechanistic studies revealed that B2 powerfully induced reactive oxygen species (ROS) burst in bacterial cells, caused oxidative damage, and thereby led bacterial apoptosis. Histopathological analysis demonstrated B2 significantly suppressed bacterial burden within infected plant tissues. These synergistic effects collectively enabled exceptional control efficacy against plant bacterial diseases, with acceptable biosafety profiles.

These findings established βC derivatives as promising lead compounds for developing efficient agrochemicals, while providing new insights regarding ROS-inducing agents to enhance food security. © 2026 Society of Chemical Industry.