New inhibitors of bacterial topoisomerase GyrA/ParC subunits

Abstract

Inhibitors of the GyrA and ParC subunits of the bacterial type IIA topoisomerases DNA gyrase and topoisomerase IV, respectively, belong to classes of antibiotics that are among the most successful of the past 50 years, both in a therapeutic and a commercial sense. The initial promise of progressive modification of an antibiotic scaffold to extend the antibacterial spectrum and to modulate pharmacokinetic/pharmacodynamic parameters of existing antibiotics in an advantageous manner has been tempered by the frequent concomitant appearance of serious toxicity. The merits of the most prominent novel antibiotics that have reached, or are expected to reach the clinical phase of drug development are summarized in this review.