PDF(Pubmed)
Abstract：
The research on pharmacology usually focuses on the structure-activity relationships of drugs, such as antibiotics, to enhance their activity, but often ignores their optical properties. However, investigating the photophysical properties of drugs is of great significance because they could be used to in situ visualize their positions and help us to understand their working metabolism. In this work, we identified a class of commercialized antibiotics, such as levofloxacin, norfloxacin, and moxifloxacin (MXF) hydrochloride, featuring the unique aggregation-induced emission (AIE) characteristics. By taking advantage of their AIE feature, antibiotic metabolism in cells could be in situ visualized, which clearly shows that the luminescent aggregates accumulate in the lysosomes. Moreover, after a structure-activity relationship study, we found an ideal site of MXF to be modified with a triphenylphosphonium and an antibiotic derivative MXF-P was prepared, which is able to specifically differentiate bacterial species after only 10 min of treatment. Moreover, MXF-P shows highly effective broad-spectrum antibacterial activity, excellent therapeutic effects and biosafety for S. aureus-infected wound recovery. Thus, this work not only discovers the multifunctionalities of the antibiotics but also provides a feasible strategy to make the commercialized drugs more powerful.
摘要：
药理学的研究通常集中在药物的构效关系,比如抗生素，为了加强他们的活动，但经常忽略它们的光学特性。然而,研究药物的光物理性质具有重要意义，因为它们可以用来原位可视化它们的位置，并帮助我们了解它们的工作代谢。在这项工作中,我们确定了一类商业化的抗生素，比如左氧氟沙星,诺氟沙星,和莫西沙星（MXF）盐酸盐，具有独特的聚集诱导发射(AIE)特性。通过利用他们的AIE功能，细胞中的抗生素代谢可以原位可视化，这清楚地表明发光聚集体在溶酶体中积累。此外，经过结构-活动关系研究，我们发现了一个理想的MXF位点被三苯基鳞修饰，并制备了抗生素衍生物MXF-P，它能够在仅10分钟的处理后特异性区分细菌种类。此外，MXF-P具有高效的广谱抗菌活性,对金黄色葡萄球菌感染的伤口恢复具有优异的治疗效果和生物安全性。因此，这项工作不仅发现了抗生素的多功能性，而且为使商业化药物更强大提供了可行的策略。
