Verderosa Anthony D, Dhouib Rabeb, Fairfull-Smith Kathryn E, Totsika Makrina
School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, QLD 4001, Australia.
Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD 4006, Australia.
Antibiotics (Basel). 2019 Mar 4;8(1):19. doi: 10.3390/antibiotics8010019.
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) exhibited significant suppression of fluorescence (>36-fold), which could be restored via radical trapping (fluoroquinolone-methoxyamine ) or reduction to the corresponding hydroxylamine . Importantly, FN 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.
荧光探针广泛用于对活细胞中的动态过程进行成像和测量。荧光抗生素是用于研究抗生素与细菌相互作用、抗菌耐药性以及阐明抗生素作用模式的宝贵工具。前荧光型氮氧化物是用于可视化和监测生物系统中细胞内自由基和氧化还原过程的“开启型”荧光探针。在此，我们将氟喹诺酮核心结构固有的荧光和抗菌特性与氮氧化物的荧光抑制能力相结合，制备出首个前荧光型氟喹诺酮 - 氮氧化物探针。氟喹诺酮 - 氮氧化物（FN）表现出显著的荧光抑制（>36倍），可通过自由基捕获（氟喹诺酮 - 甲氧基胺）或还原为相应的羟胺来恢复。重要的是，FN能够进入革兰氏阳性和革兰氏阴性细菌细胞，在进入细胞时发出可测量的荧光信号（开启），并保留抗菌活性。总之，前荧光型氮氧化物抗生素为可视化抗生素与细菌的相互作用以及研究细胞内化学过程提供了一种新的强大工具。
