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In this study, a series of novel derivatives containing the isopropanolamine moiety linked to various substituted phenols and piperazines were designed, synthesized and screened.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Antibacterial activity results showed that most compounds had good inhibitory effects on <jats:italic>Xoo<\/jats:italic>, among which compound <jats:bold>W2<\/jats:bold> (EC<jats:sub>50<\/jats:sub>\u2009=\u20092.74\u2009\u03bcg\u2009mL<jats:sup>\u22121<\/jats:sup>) exhibited the most excellent inhibitory activity, and <jats:bold>W2<\/jats:bold> also had a certain curative effect (35.89%) on rice compared to thiodiazole copper (<jats:bold>TC<\/jats:bold>) (21.57%). Scanning electron microscopy (SEM) results indicated that compound <jats:bold>W2<\/jats:bold> could cause rupture of the <jats:italic>Xoo<\/jats:italic> cell membrane. Subsequently, proteomics and quantitative real\u2010time polymerase chain reaction revealed that compound <jats:bold>W2<\/jats:bold> affected the physiological processes of <jats:italic>Xoo<\/jats:italic> and may exert antibacterial activity by targeting the two\u2010component system pathway. Interestingly, <jats:bold>W2<\/jats:bold> upregulated <jats:italic>Xoo<\/jats:italic>'s methyltransferase to impact on its pathogenicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>The present study offers a promising phenolic\u2010piperazine\u2010sopropanolamine compound as an innovative antibacterial strategy by specifically targeting the two\u2010component system pathway and inducing upregulation of methyltransferase to effectively impact <jats:italic>Xoo<\/jats:italic>'s pathogenicity. \u00a9 2024 Society of Chemical Industry.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ps.7986","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T07:04:30Z","timestamp":1707980670000},"page":"2710-2723","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Design, synthesis, antibacterial evaluation of isopropylamine linked with different substituted phenol and piperazine novel derivatives"],"prefix":"10.1002","volume":"80","author":[{"given":"Wen\u2010Hang","family":"Wang","sequence":"first","affiliation":[{"name":"College of Pharmacy Guizhou University  Guiyang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu\u2010Rui","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmacy Guizhou University  Guiyang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan\u2010Xue","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Pharmacy Guizhou University  Guiyang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Pharmacy Guizhou University  Guiyang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Pharmacy Guizhou University  Guiyang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng\u2010Peng","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmacy Guizhou University  Guiyang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Hui","family":"Shao","sequence":"additional","affiliation":[{"name":"College of Pharmacy Guizhou University  Guiyang People's Republic of China"},{"name":"National Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education Center for R&amp;D of Fine Chemicals of Guizhou University  Guiyang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue\u2010Mei","family":"Qiu","sequence":"additional","affiliation":[{"name":"College of Pharmacy Guizhou University  Guiyang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Pharmacy Guizhou University  Guiyang People's Republic of China"},{"name":"National Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education Center for R&amp;D of Fine Chemicals of Guizhou University  Guiyang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai\u2010Tao","family":"Long","sequence":"additional","affiliation":[{"name":"College of Pharmacy Guizhou University  Guiyang People's Republic of China"},{"name":"Guizhou Engineering Laboratory for Synthetic Drugs Guizhou University  Guiyang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan\u2010Ping","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Pharmacy Guizhou University  Guiyang People's Republic of China"},{"name":"Guizhou Engineering Laboratory for Synthetic Drugs Guizhou University  Guiyang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui\u2010Ping","family":"Ouyang","sequence":"additional","affiliation":[{"name":"College of Pharmacy Guizhou University  Guiyang People's Republic of China"},{"name":"National Key Laboratory of Green Pesticide, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education Center for R&amp;D of Fine Chemicals of Guizhou University  Guiyang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi\u2010Qiang","family":"Rong","sequence":"additional","affiliation":[{"name":"Frontiers Science Center for Flexible Electronics (FSCFE), Shaanxi Institute of Flexible Electronics (SIFE) &amp; 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