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This context has drawn considerable attention to the imidazothiazole scaffold, a structure frequently found in both natural products and synthetic pharmaceuticals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      A series of novel compounds featuring imidazothiazole\u2010based heterocyclic frameworks were designed and synthesized. The\n                      <jats:italic>in vitro<\/jats:italic>\n                      antifungal efficacy of these target compounds was assessed against six fungal pathogens. Among them, compounds\n                      <jats:bold>A5<\/jats:bold>\n                      and\n                      <jats:bold>E1<\/jats:bold>\n                      displayed the most potent inhibitory activity against\n                      <jats:italic>Valsa mali<\/jats:italic>\n                      , with median effective concentration (EC\n                      <jats:sub>50<\/jats:sub>\n                      ) values of 1.31 and 1.34\u2009mg L\n                      <jats:sup>\u22121<\/jats:sup>\n                      , respectively, which significantly outperformed the positive control boscalid (EC\n                      <jats:sub>50<\/jats:sub>\n                      \u2009=\u200913.91\u2009mg L\n                      <jats:sup>\u22121<\/jats:sup>\n                      ).\n                      <jats:italic>In vivo<\/jats:italic>\n                      trials demonstrated that compound\n                      <jats:bold>A5<\/jats:bold>\n                      showed remarkable protective and curative effects, achieving 53.14% (protective) and 68.44% (curative) at a concentration of 50\u2009mg L\n                      <jats:sup>\u22121<\/jats:sup>\n                      , comparable to boscalid (59.16% and 64.63%). Preliminary mechanistic insights were gained through a combination of confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and physiological and biochemical assays. Acute toxicity assessments classified compound\n                      <jats:bold>A5<\/jats:bold>\n                      as low\u2010toxic to zebrafish, earthworms, and worker bees.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      This study reports that the imidazothiazole derivative\n                      <jats:bold>A5<\/jats:bold>\n                      exhibits potent\n                      <jats:italic>in vitro<\/jats:italic>\n                      activity against\n                      <jats:italic>V. mali<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      efficacy comparable to a commercial fungicide. Additionally, compound\n                      <jats:bold>A5<\/jats:bold>\n                      shows low environmental toxicity, positioning it as a promising lead candidate for the development of next\u2010generation, low\u2010risk fungicides. \u00a9 2026 Society of Chemical Industry.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ps.70546","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T02:00:32Z","timestamp":1768788032000},"page":"4332-4346","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Design, synthesis and biological evaluation of imidazo[5,1\u2010b]thiazole derivatives: antifungal activity and mechanism of action"],"prefix":"10.1002","volume":"82","author":[{"given":"Yaping","family":"Song","sequence":"first","affiliation":[{"name":"School of Plant Protection and College of Materials and Chemistry Anhui Agricultural University  Hefei 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