Quinolone Antimicrobials: A Medicinal Chemistry Perspective on Structural Evolution, Pharmacology, and Computational Profiling

Quinolones are among the most successful antibacterial drugs developed in the last century. These drugs act selectively by inhibiting bacterial type II topoisomerases (DNA gyrase and topoisomerase IV), thereby impairing DNA replication and transcription. In the more than sixty years since the first quinolone entered the market, several others have been developed and classified into four generations according to their chemical modifications and effects on the spectrum of antibacterial activity. This review aims to provide an updated overview on this class of antimicrobials for scientists and clinicians doing research in the field of quinolones. We considered perspectives from several areas of medicinal chemistry, including the historical development and chemical evolution of quinolones, as well as their pharmacodynamics and mechanism of action, pharmacokinetics, and toxicity. Additionally, we integrated modern computational and analytical approaches, including bibliometric analysis, molecular docking, and drug-likeness profiling of quinolones to further understand their evolution and development.