Discovery of xanthone-based nitric oxide donors targeting biofilm clearance

文献类型： 外文期刊

第一作者： Tang, Qun

作者： Tang, Qun;Ye, Wenchong;Lv, Sai;Zhang, Keyu;Han, Xiangan;Wang, Chunmei;Wang, Xiaoyang;Zhou, Wen;Tang, Qun;Ye, Wenchong;Lv, Sai;Zhang, Keyu;Wang, Chunmei;Wang, Xiaoyang;Zhou, Wen;Chandarajoti, Kasemsiri;Chandarajoti, Kasemsiri;Ge, Rile;Bai, Han

作者机构：

关键词： biofilm clearance; biofilm infection; nitric oxide (NO); alpha-mangostin-based NO donors

期刊名称：ARCHIV DER PHARMAZIE （ 影响因子：3.6； 五年影响因子：4.2 ）

ISSN： 0365-6233

年卷期： 2025 年 358 卷 1 期

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收录情况： SCI

摘要： Bacteria biofilm infection seriously challenges clinical drug therapy. Nitric oxide (NO) was reported to disperse biofilm, eliminate bacteria resistance and kill bacteria. In this study, on the basis of membrane targeting of alpha-mangostin (alpha-MG) and the dispersion effect of NO on bacteria biofilms, we designed and synthesized 30 NO donors that alpha-MG was conjugated with a nitrobenzene or a nitrate and other four representative reference derivatives. Compound 23 with 2-chloro-4-nitrobenzoyl introduced in the position C6 of alpha-MG exhibited the prominent ability to eradicate Staphylococcous aureus biofilm, and a more long-lasting and stable bactericidal effect in vitro, and lower hemolytic activity over alpha-MG. Moreover, a mouse wound model infected by S. aureus biofilm supported the in vivo reduced bacterial burden closely associated with the NO release from compound 23 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.

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