Bacterial topoisomerase inhibitors: Quinolones and beyond

Abstract

Previous studies have established the essentiality of the bacterial DNA replication process and its requisite enzymes including DNA gyrase and topoisomerase IV. The quinolone class of antibiotics provided a clinical validation of these targets and has been widely used over the past 50 years. A number of more recent examples of these compounds are described herein. Two related, but structurally distinct quinolone-like compounds are also discussed. Non-quinolones, designated novel bacterial type II topoisomerase inhibitors (NBTIs), have been explored and several examples are provided in this work. Successful development of these latter compounds could enhance and extend the clinical utility of bacterial topoisomerase inhibitors beyond the clinically valuable and commercially successful quinolone antibiotics. Bacterial topoisomerase inhibitors should continue to play an important role in the battle against bacterial pathogens for many years to come.