Over the past fifteen years, fluoroquinolones have gained substantial prominence in the therapy of bacterial infections. Ciprofloxacin is still the most widely used agent in this class, due to its broad spectrum and excellent oral bioavailability [1]. Further development of the structure-activity relationships (SAR) in the fluoro-quinolone class has produced a large number of new quinolones, many of which have been advanced to clinical testing in the last decade. Most of these new agents possess improved activity against Gram-positive pathogens compared to cipro-floxacin, and some have potent activity against anaerobes and pathogens that are resistant to many other groups of antimicrobials [2]. The myriad structural modifications that have been investigated have also led to improvements in pharmacokinetic properties and lessening of a number of adverse effects.

The mechanism of action of these new agents, however, is still inhibition of bacterial topoisomerases. The enzyme DNA gyrase was originally identified as the target of the quinolones and remains a major focus of research. The more recently discovered topoisomerase IV provides a second target for the fluoroquinolones (see the section on "Mechanism of Action").

This chapter describes the SAR that has been exploited to provide new fluoroquinolones with potent activity and favorable in vivo properties, and discusses the most recent advances made in our knowledge concerning the mechanism by which fluoroquinolones kill bacteria.

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