Profluorescent Fluoroquinolone-Nitroxides for Investigating Antibiotic–Bacterial Interactions

Antibiotics

Makrina Totsika¹  Rabeb Dhouib¹  KathrynE. Fairfull-Smith²  AnthonyD. Verderosa² 

[1] Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD 4006, Australia;School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, QLD 4001, Australia;

关键词: antibiotics;    fluorescent antibiotics;    fluorescent probes;    fluoroquinolones;    profluorescent nitroxides;    nitroxides;   

DOI  :  10.3390/antibiotics8010019

来源: DOAJ

【 摘 要 】

Fluorescent probes are widely used for imaging and measuring dynamic processes in living cells. Fluorescent antibiotics are valuable tools for examining antibiotic–bacterial interactions, antimicrobial resistance and elucidating antibiotic modes of action. Profluorescent nitroxides are ‘switch on’ fluorescent probes used to visualize and monitor intracellular free radical and redox processes in biological systems. Here, we have combined the inherent fluorescent and antimicrobial properties of the fluoroquinolone core structure with the fluorescence suppression capabilities of a nitroxide to produce the first example of a profluorescent fluoroquinolone-nitroxide probe. Fluoroquinolone-nitroxide (FN) 14 exhibited significant suppression of fluorescence (>36-fold), which could be restored via radical trapping (fluoroquinolone-methoxyamine 17) or reduction to the corresponding hydroxylamine 20. Importantly, FN 14 was able to enter both Gram-positive and Gram-negative bacterial cells, emitted a measurable fluorescence signal upon cell entry (switch on), and retained antibacterial activity. In conclusion, profluorescent nitroxide antibiotics offer a new powerful tool for visualizing antibiotic–bacterial interactions and researching intracellular chemical processes.

【 授权许可】

Unknown