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Abstract
Infections caused by antibiotic resistant bacteria are a major health concern throughout the world. It is well known that PFK-158 can enhance the antibacterial effect of polymyxin, but its own anti-bactericidal effect is rarely discussed. In order to investigate the anti-bactericidal effect of PFK-158 and its derivatives, PFK-158 and 35 derivatives were designed, synthesized, and evaluated for their antibacterial activities. Compounds A1, A3, A14, A15 and B6 exhibited potent antibacterial effect against both clinical drug sensitive and resistant Gram-positive bacteria, and they are 2–8 folds more potent than levofloxacin against Methicillin-resistant staphylococcus epidermidis (MRSE). A significant synergistic effect of these compounds and polymyxin against drug-resistant Gram-negative bacteria, which is similar to PFK-158 was also observed. The result can provided a new and broader prospect for the development of new medicine against drug-resistant bacteria.
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