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In this study, on the basis of membrane targeting of \u03b1\u2010mangostin (\u03b1\u2010MG) and the dispersion effect of NO on bacteria biofilms, we designed and synthesized 30 NO donors that \u03b1\u2010MG was conjugated with a nitrobenzene or a nitrate and other four representative reference derivatives. Compound <jats:bold>23<\/jats:bold> with 2\u2010chloro\u20104\u2010nitrobenzoyl introduced in the position C6 of \u03b1\u2010MG exhibited the prominent ability to eradicate <jats:italic>Staphylococcous aureus<\/jats:italic> biofilm, and a more long\u2010lasting and stable bactericidal effect in vitro, and lower hemolytic activity over \u03b1\u2010MG. Moreover, a mouse wound model infected by <jats:italic>S. aureus<\/jats:italic> biofilm supported the in vivo reduced bacterial burden closely associated with the NO release from compound <jats:bold>23<\/jats:bold> that exerted a dispersing effect on biofilms. Therefore, our design strategy can provide a promising and effective solution to intervene in biofilm infection with high specificity.<\/jats:p>","DOI":"10.1002\/ardp.202400793","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T07:25:07Z","timestamp":1734938707000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Discovery of xanthone\u2010based nitric oxide donors targeting biofilm clearance"],"prefix":"10.1002","volume":"358","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4682-5663","authenticated-orcid":false,"given":"Qun","family":"Tang","sequence":"first","affiliation":[{"name":"Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences  Shanghai China"},{"name":"Key laboratory of Veterinary Chemical Drugs and Pharmaceutics, Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences  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