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It has broad\u2010spectrum 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      The results showed that compounds\n                      <jats:bold>A6<\/jats:bold>\n                      ,\n                      <jats:bold>A9<\/jats:bold>\n                      ,\n                      <jats:bold>B2<\/jats:bold>\n                      ,\n                      <jats:bold>B4<\/jats:bold>\n                      ,\n                      <jats:bold>H<\/jats:bold>\n                      ,\n                      <jats:bold>G1<\/jats:bold>\n                      , and\n                      <jats:bold>K<\/jats:bold>\n                      with berberine parent structure showed excellent antibacterial activity. Interestingly, compared with natural berberine analogues, the\n                      <jats:bold>H<\/jats:bold>\n                      series of compounds showed the strongest antibacterial activity, and their minimum inhibitory concentration (MIC) values against\n                      <jats:italic>Xoo<\/jats:italic>\n                      ,\n                      <jats:italic>Xac<\/jats:italic>\n                      , and\n                      <jats:italic>Rs<\/jats:italic>\n                      were less than 50\u2009\u03bcg\u2009mL\n                      <jats:sup>\u22121<\/jats:sup>\n                      . Among them, compounds\n                      <jats:bold>H5<\/jats:bold>\n                      and\n                      <jats:bold>H6<\/jats:bold>\n                      exhibited the strongest antibacterial activity, and the MIC values for\n                      <jats:italic>Xoo<\/jats:italic>\n                      and\n                      <jats:italic>Rs<\/jats:italic>\n                      were 6.25\u2009\u03bcg\u2009mL\n                      <jats:sup>\u22121<\/jats:sup>\n                      . The preliminary mechanism showed that compound\n                      <jats:bold>H6<\/jats:bold>\n                      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.\n                      <jats:italic>In vivo<\/jats:italic>\n                      experiments show that the protective efficacies of compound\n                      <jats:bold>H6<\/jats:bold>\n                      and thiodiazole copper at 800\u2009\u03bcg\u2009mL\n                      <jats:sup>\u22121<\/jats:sup>\n                      were 34.10% and 24.08%, respectively, and the curative efficacies were 26.91% and 23.98%, respectively. These results indicate that the\n                      <jats:italic>in vivo<\/jats:italic>\n                      protective effect of\n                      <jats:bold>H6<\/jats:bold>\n                      was better than that of the positive drug thiodiazole copper.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Compound\n                      <jats:bold>H6<\/jats:bold>\n                      is expected to be a new type of broad\u2010spectrum bactericide for exhibiting excellent bactericidal activities, which is worthy of further investigation. \u00a9 2026 Society of Chemical Industry.\n                    <\/jats:p>\n                  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