Structural modification of berberine to obtain novel antibacterial isoquinoline derivatives against phytopathogenic bacteria

BACKGROUND Berberine is a quaternary ammonium alkaloid natural product containing an isoquinoline skeleton. It has broad‐spectrum pharmacological activity and plays a key leading compound role in the development of new drugs. Inspired by natural berberine analogues, 51 novel berberine derivatives were designed and synthesized through structural modification, and their bactericidal activities against plantpathogenic bacteria were evaluated. RESULTS The results showed that compounds A6 , A9 , B2 , B4 , H , G1 , and K with berberine parent structure showed excellent antibacterial activity. Interestingly, compared with natural berberine analogues, the H series of compounds showed the strongest antibacterial activity, and their minimum inhibitory concentration (MIC) values against Xoo , Xac , and Rs were less than 50 μg mL −1 . Among them, compounds H5 and H6 exhibited the strongest antibacterial activity, and the MIC values for Xoo and Rs were 6.25 μg mL −1 . The preliminary mechanism showed that compound H6 could inhibit the formation of biofilm, inhibit the production of exopolysaccharides, increase the level of reactive oxygen species, destroy the normal morphology of cells, and had low toxicity to plants. In vivo experiments show that the protective efficacies of compound H6 and thiodiazole copper at 800 μg mL −1 were 34.10% and 24.08%, respectively, and the curative efficacies were 26.91% and 23.98%, respectively. These results indicate that the in vivo protective effect of H6 was better than that of the positive drug thiodiazole copper. CONCLUSION Compound H6 is expected to be a new type of broad‐spectrum bactericide for exhibiting excellent bactericidal activities, which is worthy of further investigation.