Nitroxoline (DB01422): A Comprehensive Monograph on an Established Antibiotic with Emerging Therapeutic Potential

Executive Summary

Nitroxoline is a small molecule drug of the 8-hydroxyquinoline class that has occupied a unique niche in the therapeutic landscape for over half a century. Initially introduced in the 1960s, it has been established primarily in European and select global markets as a reliable oral uroantiseptic for the treatment and prophylaxis of urinary tract infections (UTIs). Its enduring clinical utility is rooted in a distinctive mechanism of action that sets it apart from nearly all other antibiotic classes. The primary antimicrobial effect of Nitroxoline is not target-specific enzyme inhibition but rather the chelation of essential divalent metal cations, such as magnesium, manganese, iron, and zinc. This fundamental process disrupts multiple bacterial enzymatic functions, most notably RNA polymerase activity, and critically, also dismantles the protective matrix of bacterial biofilms. This mechanism has proven remarkably resilient to the development of microbial resistance, a feature of profound importance in an era of escalating antimicrobial resistance.

Despite its long history, comprehensive knowledge of Nitroxoline's pharmacokinetic profile, according to modern regulatory standards, remains notably deficient. This data gap has historically constrained its application to localized infections of the urinary tract, where its rapid absorption and high-concentration urinary excretion ensure therapeutic efficacy. However, the very properties that define its antimicrobial action have recently propelled it to the forefront of drug repurposing research, particularly in the field of oncology.