Title:Moxifloxacin Derivatives with Potential Antibacterial Activity against Methicillin- Resistant Staphylococcus Aureus (MRSA)
Volume: 21
Issue: 27
Author(s): Rongxing Chen, Huarui Xue, Yazhou Xu, Tianwei Ma, Yuan Liu, Jing Zhang, Xiangkui Shi*Dong Guo*
Affiliation:
- Maternal and Child Health Hospital of Xuzhou Medical University, Jiangsu Province,China
- School of Pharmacy, Xuzhou Medical University, Jiangsu Province,China
Keywords:
Moxifloxacin, 1, 2, 3-triazole, Isatin, Antibacterial, Drug resistance, MRSA.
Abstract:
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 μg/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.