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Although antibacterial agents are available, their application is constrained by drug resistance, environmental hazards, and inadequate sustainability. Development of novel and effective antimicrobial agents has become urgent imperative. A series of morpholine-containing 1,3,4-thiadiazole derivatives were designed and synthesized. Compound H6 exhibited the most potent inhibitory activity against Xanthomonas oryzaepv oryzae (Xoo), with EC50 of 1.21 \u03bcg\/mL\u2013significantly lower than bismerthiazol (EC50 = 64.71 \u03bcg\/mL) and thiodiazole-copper (EC50 = 63.94 \u03bcg\/mL). Mechanistic studies revealed H6 inhibits biofilm and extracellular polysaccharide formation, disrupts membrane integrity, induces ROS accumulation, and promotes lipid peroxidation. Transcriptomic analysis demonstrated significant downregulation of key virulence genes (vgrG, accC, MCP), indicating attenuated pathogenicity. These results underscore H6 as a promising bactericidal agent, demonstrating considerable potential in sustainable management of plant bacterial diseases.<\/jats:p>","DOI":"10.1021\/acs.jafc.5c17399","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T02:18:51Z","timestamp":1784686731000},"page":"23282-23293","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis,\nand Mechanistic Investigation of\nNovel 1,3,4-Thiadiazole Derivatives Bearing a Morpholine Moiety Against\n                    <i>Xanthomonas oryzae<\/i>\n                    pv\n                    <i>Oryzae<\/i>"],"prefix":"10.1021","volume":"74","author":[{"given":"Mengzhi","family":"Yang","sequence":"first","affiliation":[{"name":"Center for R&D of Fine Chemicals of Guizhou University , , , ,","place":["Guiyang, Guizhou, People\u2019s Republic of China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengpeng","family":"Li","sequence":"additional","affiliation":[{"name":"Guizhou University , , , ,","place":["Guiyang, Guizhou, People\u2019s Republic of China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhou","sequence":"additional","affiliation":[{"name":"Guizhou University , , , ,","place":["Guiyang, Guizhou, People\u2019s Republic of China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhurui","family":"Li","sequence":"additional","affiliation":[{"name":"Guizhou University , , , ,","place":["Guiyang, Guizhou, People\u2019s Republic of China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9851-037X","authenticated-orcid":true,"given":"Danping","family":"Chen","sequence":"additional","affiliation":[{"name":"Guizhou University , , , ,","place":["Guiyang, Guizhou, People\u2019s Republic of China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5710-7210","authenticated-orcid":true,"given":"Bingqian","family":"Liu","sequence":"additional","affiliation":[{"name":"Guizhou University , , , ,","place":["Guiyang, Guizhou, People\u2019s Republic of China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2956-7639","authenticated-orcid":true,"given":"Chenchen","family":"Li","sequence":"additional","affiliation":[{"name":"Guizhou University , , , ,","place":["Guiyang, Guizhou, People\u2019s Republic of China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1972-2834","authenticated-orcid":true,"given":"Song","family":"Bai","sequence":"additional","affiliation":[{"name":"Guizhou Industry Polytechnic College , , ,","place":["Guiyang, Guizhou, People\u2019s Republic of China, 550008"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1859-0128","authenticated-orcid":true,"given":"Zhenchao","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for R&D of Fine Chemicals of Guizhou University , , , ,","place":["Guiyang, Guizhou, People\u2019s Republic of China, 550025"]},{"name":"Guizhou University , , , ,","place":["Guiyang, Guizhou, People\u2019s Republic of China, 550025"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"issue":"1","key":"2026080510110127000_cit1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s12284-019-0358-y","article-title":"Resistance Genes and\nTheir Interactions with Bacterial Blight\/Leaf Streak Pathogens (Xanthomonas Oryzae) in Rice (Oryza Sativa L.)\u2013an Updated Review","volume":"13","author":"Jiang","year":"2020","journal-title":"Rice"},{"issue":"3","key":"2026080510110127000_cit2","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1002\/ps.7834","article-title":"Discovery of Tryptanthrin\nAnalogues Bearing F and Piperazine\nMoieties as Novel Phytopathogenic Antibacterial and Antiviral Agents","volume":"80","author":"Zhang","year":"2024","journal-title":"Pest Manag. 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