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Croatica Chemica Acta, Vol. 98 No. 2, 2025.

Review article

https://doi.org/10.5562/cca4187

Small Molecule, Big Potential – Nitroxoline in the Era of Rising Antimicrobial Resistance

Mirna Petković Didović orcid id orcid.org/0000-0002-6028-5429 ; Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia *
Davorka Repac Antić orcid id orcid.org/0000-0003-4496-7996 ; Department of Microbiology and Parasitology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia
Davor Kopilović ; Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia
Sugita Komić ; Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia
Ivana Gobin ; Department of Microbiology and Parasitology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia

* Corresponding author.

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Abstract

Nitroxoline (NTX), a synthetic 8-hydroxyquinoline derivative, has re-emerged as a promising antimicrobial agent amid the global rise in antimicrobial resistance (AMR). Despite over 60 years of clinical use, resistance to NTX remains remarkably low. Its unique mode of action, based on metal ion chelation, distinguishes it from conventional antimicrobials and underpins its pleiotropic effects, including anticancer, antiviral, antifungal, antibiofilm, and antiparasitic activities. This review explores NTX’s historical development, chemical properties, coordination chemistry, and multifaceted mechanisms of action, as well as its limitations. Special emphasis is placed on its efficacy against multidrug-resistant pathogens, biofilm-associated infections, and its repurposing potential in oncology and parasitology. The paper also highlights critical knowledge gaps, particularly in thermodynamic data for metal complexes, and calls for renewed clinical and pharmacological evaluation. Despite certain limitations, its excellent safety profile, low resistance rates, and broad-spectrum activity makes NTX a valuable, underutilized therapeutic with significant potential for repositioning in modern medicine.

Keywords

antimicrobial resistance; nitroxoline; chelation; biofilm; antibiotics; repurposing; multidrug-resistant bacteria; antimicrobials; antifungals; anticancer; antitumour; amoebae

Hrčak ID:

339967

URI

https://hrcak.srce.hr/339967

Publication date:

9.7.2025.

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