Quinolones: The Cornerstone of the Advanced Era in Therapeutics

Quinolones are nitrogen-containing heterocyclic compounds that exist in natural, semisynthetic, and synthetic forms, and play a vital role as antibiotics. Their complex structure and numerous potential modifications have made them a significant focus in synthetic chemistry over the past two to three decades. The most common compound associated with quinolones is nalidixic acid, which was discovered long ago. Since then, various researchers have focused on this core as a potential pharmacophore or starting nucleus for developing new drug candidates to manage diseases, such as cancer, urinary tract infections, Alzheimer's, and tuberculosis. In this paper, we aimed to summarize the activities of quinolone hybrids discovered over the past decades. The article delivers a thorough overview of quinolones with emphasis on synthetic innovations, their mechanism of action, resistance evasion, and classification from generation to generation, along with the newer agents. Furthermore, emerging concepts, including modulation of SOS response, induction of oxidative stress, and impact of sub-inhibitory concentrations, are also explored as supplementary strategies to enhance antibacterial efficacy. Beyond their well-known antibacterial activity, quinolones also exhibit a broad range of pharmacological properties, including antimalarial, antifungal, antiinflammatory, antitubercular, anticancer, antiviral, and immunomodulatory effects. This review highlights both their diverse clinical applications and the challenges associated with their use. This article also provides a knowledgeable asset for acknowledging quinolones' chemistry, pharmacology, and future therapeutic potential.