Moxifloxacin Derivatives with Potential Antibacterial Activity against Me- thicillin-Resistant Staphylococcus Aureus (MRSA)

Background: Methicillin-resistant S. aureus (MRSA) has already tormented humanity and the environment for a long time and is responsible for many difficult-to-treat infections. Unfortunately, there are limited therapeutic options, and MRSA isolates with complete resistance to vancomycin, the first-line drug for the treatment of MRSA infections, have already emerged in recent years. Moxifloxacin retained activity against mutant bacterial strains with various levels of fluoroquinolones resistance and had a lower potential to select for resistant mutants. Isatin is a versatile structure, and its derivatives are potent inhibitors of many enzymes and receptors. The fluoroquinolone-isatin derivatives demonstrated excellent antibacterial activity against both drug-sensitive and drug-resistant organisms. The structure-activity relationship elucidated that incorporation of 1,2,3-triazole moiety into the C-7 position of fluoroquinolone skeleton was favorable to the antibacterial activity. Accordingly, fluoroquinolone derivatives with isatin and 1,2,3-triazole fragments at the side chain on the C-7 position are promising candidates to fight against drug-resistant bacteria. Objective: To explore more active moxifloxacin derivatives to fight against MRSA and enrich the structure-activity relationships. Methods: The synthesized moxifloxacin derivatives 7a-i and 14a-f were evaluated for their antibacterial activity against a panel of MRSA strains by means of standard two-fold serial dilution method. Results: The majority of the synthesized moxifloxacin derivatives were active against most of the tested MRSA strains with MIC values in a range of 1 to 64 mu g/mL. The mechanistic investigations revealed that topoisomerase IV was one of the targets for antibacterial activity. Conclusion: These derivatives are useful scaffolds for the development of novel topoisomerase IV inhibitors.

Automated summary

The study aimed to explore more active moxifloxacin derivatives to combat MRSA and found that the majority of the synthesized derivatives exhibited activity against MRSA strains, with one of the targets for antibacterial activity being topoisomerase IV. These derivatives may serve as useful scaffolds for the development of novel topoisomerase IV inhibitors.