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Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Research Article

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

Author(s): Rongxing Chen, Huarui Xue, Yazhou Xu, Tianwei Ma, Yuan Liu, Jing Zhang, Xiangkui Shi* and Dong Guo*

Volume 21 , Issue 27 , 2021

Published on: 13 October, 2021

Page: [2474 - 2482] Pages: 9

DOI: 10.2174/1568026621666211013125551

Price: $65


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.

Keywords: Moxifloxacin, 1, 2, 3-triazole, Isatin, Antibacterial, Drug resistance, MRSA.

Graphical Abstract

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