Photoactive NO hybrids with pseudo-zero-order release kinetics for antimicrobial applications.
Photoactive NO hybrids with pseudo-zero-order release kinetics for antimicrobial applications.
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DOI：
10.1039/d0ob00564a
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发表时间：
2020-07
影响因子：
3.2
通讯作者：
Yongfang Liao;Zizhen Ye;Meng Qian;Xing Wang;Yuda Guo;Guifang Han;Yuguang Song;Jingli Hou
中科院分区：
文献类型：
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作者：
Yongfang Liao;Zizhen Ye;Meng Qian;Xing Wang;Yuda Guo;Guifang Han;Yuguang Song;Jingli Hou
细菌感染是威胁人类健康和生命的主要因素之一，细菌耐药性的产生与生物膜的形成有关。一氧化氮（NO）已成为调节生物膜形成的重要因素。为了利用NO的潜在益处并开发有效的抗菌剂，我们设计并合成了一类新的NO杂化物，其中活性支架苯并噻吩并氮杂卓用亚硝基标记并进一步与季铵或膦缀合。NO从这些杂化物的暂时释放可以通过光活化来实现。有趣的是，NO的释放遵循伪零级动力学，这很容易通过测量荧光苯并噻吩并氮杂卓或NO来确定。与阳性对照环丙沙星相比，具有三苯基膦（TPP）的NO杂合物表现出更有效的抗S.金黄色葡萄球菌生物膜。照射NO杂合物对S.与黑暗中的亲本NO杂合体或相应的NO释放产物相比，金黄色葡萄球菌生物膜中的NO含量增加，表明NO和NO释放产物的组合作用。因此，这类新的NO杂化物包含非常有前途的抗菌剂，并且这项工作为设计高效抗菌剂提供了新的途径。
Bacterial infection is a major threat to the health and life of humans due to the development of drug resistance, which is related to biofilm formation. Nitric oxide (NO) has emerged as an important factor in regulating biofilm formation. In order to harness the potential benefits of NO and develop effective antibacterial agents, we designed and synthesized a new class of NO hybrids in which the active scaffold benzothienoazepine was tagged with a nitroso group and further conjugated with quaternary ammoniums or phosphoniums. The temporal release of NO from these hybrids can be achieved by photoactivation. Interestingly, the NO release follows a pseudo-zero-order kinetics, which is easily determined by measuring the fluorescent benzothienoazepine or NO. Compared to the positive control ciprofloxacin, the NO hybrid with triphenyl phosphonium (TPP) exhibited more effective activity against S. aureus biofilm in darkness. Irradiation of the NO hybrid led to higher inhibition against S. aureus biofilm compared to the parental NO hybrid in darkness or the corresponding NO-released product, indicating the combined effect of NO and the NO-released product. Therefore, this new class of NO hybrids includes very promising antimicrobial agents and this work provides a new way for the design of highly effective antimicrobial agents.