Glycosides of Nadifloxacin-Synthesis and Antibacterial Activities against Methicillin-Resistant Staphylococcus aureus

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 ( ) 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 -linked ( ) and -linked ( ) glycosides, each of which was prepared and purified to afford single anomers. The seven glycoside derivatives ( ) were examined for potency against eight strains of , four of which were methicillin-resistant. Although less potent than free nadifloxacin ( ), the α-L-arabinofuransoside ( ) 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 ( ), raising the prospect of its use in oral applications.