Quinolones

Quinolones are antibiotics that share a bicyclic core structure related to 4-quinolone. Quinolones have been developed over four generations, with drugs ranging from nalidixic acid to ciprofloxacin and trovafloxacin available for clinical use. Quinolones inhibit DNA replication by binding to bacterial type II topoisomerase (DNA gyrase), thereby preventing it from relaxing supercoiled chromosomal DNA. A radioassay involving the use of \({ }^{14}\) C thymine, \({ }^{14}\) C uracil, and \({ }^{14}\) C arginine can be used to determine whether nalidixic acid inhibits DNA replication, transcription, or translation, respectively. Agarose gel electrophoresis can be used to determine whether ciprofloxacin inhibits the activity of gyrase on supercoiled plasmid in vitro. The X-ray crystallographic structure of quinolone-bound gyrase reveals that \(\pi \) - \(\pi \) stacking interactions and coordination with magnesium mediate this interaction.