Mode of action of sulfanilyl fluoroquinolones

Abstract

The mode of action of sulfanilyl fluoroquinolones (NSFQs) was investigated with NSFQ-104, NSFQ-105, and some structurally related compounds. Evidence arising from interactions with p-aminobenzoic acid and trimethoprim suggested that a sulfonamidelike mechanism of action makes little or no contribution to the in vitro activity of NSFQs. NSFQ-105 showed an activity that inhibits gyrase-catalyzed DNA supercoiling that is similar to the activity of other fluoroquinolones. Also, NSFQ-105 uptake was decreased by the presence of Mg2+ and increased by a lower pH. These results indicate that NSFQs having only one ionizable group could exhibit more favorable kinetics of access to the bacterial cell than zwitterionic fluoroquinolones.

FIG. 1

Accumulation of some FQs, at an external concentration of 10 μg/ml, in S. aureus ATCC 29213 over 10 min. Each point shown is the mean of at least three experiments. Symbols: □——□, NSFQ-105; □- - -□, NSFQ-105 with added 10 mM MgCl₂; ▵, ciprofloxacin; ◊, compound VI.

FIG. 2

Scheme for protonation of ZFQs.

FIG. 3

Effect of pH on the MIC (A) and the UMF (B) for S. aureus ATCC 29213. Symbols: •, NSFQ-104; □, NSFQ-105; ×, norfloxacin; ▵, ciprofloxacin.