1. Glycosides of Nadifloxacin-Synthesis and Antibacterial Activities against Methicillin-Resistant Staphylococcus aureus .
- Author
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Hutchins M, Bovill RA, Stephens PJ, Brazier JA, and Osborn HMI
- Subjects
- Fluoroquinolones pharmacology, Fluoroquinolones chemistry, Fluoroquinolones chemical synthesis, Molecular Structure, Quinolizines, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents chemical synthesis, Methicillin-Resistant Staphylococcus aureus drug effects, Glycosides chemistry, Glycosides pharmacology, Glycosides chemical synthesis, Microbial Sensitivity Tests
- Abstract
The increase in the number of bacteria that are resistant to multiple antibiotics poses a serious clinical problem that threatens the health of humans worldwide. Nadifloxacin ( 1 ) is a highly potent antibacterial agent with broad-spectrum activity. However, its poor aqueous solubility has limited its use to topical applications. To increase its solubility, it was glycosylated herein to form a range of trans -linked ( 3a-e ) and cis -linked ( 7a,b ) glycosides, each of which was prepared and purified to afford single anomers. The seven glycoside derivatives ( 3a-e, 7a,b ) were examined for potency against eight strains of S. aureus , four of which were methicillin-resistant. Although less potent than free nadifloxacin ( 1 ), the α-L-arabinofuransoside ( 3a ) was effective against all strains that were tested (minimum inhibitory concentrations of 1-8 μg/mL compared to 0.1-0.25 μg/mL for nadifloxacin), demonstrating the potential of this glycoside as an antibacterial agent. Estimation of Log P as well as observations made during preparation of these compounds reveal that the solubilities of the glycosides were greatly improved compared with nadifloxacin ( 1 ), raising the prospect of its use in oral applications.
- Published
- 2022
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