# Nitroxoline

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Antibiotic chemical compound

Pharmaceutical compound

Nitroxoline Clinical data AHFS/Drugs.com International Drug Names ATC code J01XX07 (WHO) Legal status Legal status US: IND Identifiers IUPAC name 5-nitro-quinolin-8-ol CAS Number 4008-48-4 Y PubChem CID 19910 DrugBank DB01422 Y ChemSpider 18756 Y UNII A8M33244M6 KEGG D07245 Y ChEMBL ChEMBL1454910 N CompTox Dashboard (EPA) DTXSID4046284 ECHA InfoCard 100.021.513 Chemical and physical data Formula C9H6N2O3 Molar mass 190.158 g·mol−1 3D model (JSmol) Interactive image SMILES [O-][N+](=O)c1ccc(O)c2ncccc12 InChI InChI=1S/C9H6N2O3/c12-8-4-3-7(11(13)14)6-2-1-5-10-9(6)8/h1-5,12H Y Key:RJIWZDNTCBHXAL-UHFFFAOYSA-N Y NY (what is this?) (verify)

**Nitroxoline** is an [antibiotic](/source/Antibiotic)[1] that has been in use in Europe for about fifty years, and has proven to be very effective at combating [biofilm](/source/Biofilm) infections. Nitroxoline was shown to cause a decrease in the biofilm density of *[P. aeruginosa](/source/P._aeruginosa)* infections, which would allow access to the infection by the immune system *in vivo*.[2] It was shown that nitroxoline functions by [chelating](/source/Chelating) Fe2+ and Zn2+ ions from the biofilm matrix; when Fe2+ and Zn2+ were reintroduced into the system, biofilm formation activity was restored. The biofilm degradation ability is comparable to [EDTA](/source/EDTA) derivatives, but this drug has a history of human use in clinical settings and therefore has a precedent with which to allow its use against “slimy” biofilm infections.

## Anticancer activity

The chelating activities of nitroxoline have also been used in an anticancer setting. Nitroxoline has been shown to be more [cytotoxic](/source/Cytotoxic) to [HL60](/source/HL60), DHL-4, [PANC-1](/source/PANC-1), and [A2780](https://en.wikipedia.org/w/index.php?title=A2780&action=edit&redlink=1) [[zh](https://zh.wikipedia.org/wiki/A2780)] cells lines than [clioquinol](/source/Clioquinol) and other [8-hydroxyquinoline](/source/8-hydroxyquinoline) derivatives.[3] It also demonstrated an increase in [reactive oxygen species](/source/Reactive_oxygen_species) (ROS) production over controls, especially when Cu2+ was added. The ROS levels reached over 350% of the controls with addition of CuCl2. The cytotoxicity production was markedly decreased with addition of ZnCl2, indicating, based on this model, that nitroxoline is not a zinc chelator. Because the zinc chelating action of clioquinol has been associated with [subacute myelo-optic neuropathy](/source/Subacute_myelo-optic_neuropathy), the use of nitroxoline as a cytotoxic drug in the treatment of cancers should not exhibit neurotoxic effects in humans, and *in vivo* trials on tumour xenografts in mice have not yielded any negative neurodegenerative effects.

Nitroxoline has been shown to [inhibit the enzymatic activity](/source/Enzyme_inhibitor) of [cathepsin B](/source/Cathepsin_B).[4] Cathepsin B degrades extra-cellular membrane proteins in tumor cells, allowing them to proliferate more freely, and metastasize throughout the body. Nitroxoline was shown to be a noncompetitive, reversible inhibitor of these actions in MCF-10A neoT cells. The *K*i ([dissociation constant](/source/Dissociation_constant)) values it demonstrates are comparable to other reversible inhibitors of cathepsin B. This indicates that it may be a candidate for further trials as an anticancer drug, especially given its history as an antimicrobial agent and its well-known [pharmacokinetic](/source/Pharmacokinetic) profile. The mechanism of action by which nitroxoline inhibits cathepsin B may also suggest that further research of noncovalent, noncompetitive inhibitors of cathepsin B could be warranted. In fact, it was recently shown that a balance exists between the potency and the kinetics of a molecule, reflected in the molecular weight, which must be optimized in order to create the best drug for inhibition of a target enzyme.[5] For example, a certain inhibitor may have a high affinity for an enzyme, but it may prove impractical to use in a clinical setting for treatment because of its size.

Nitroxoline and its analogues have also been shown to have [antiangiogenic](/source/Antiangiogenic) properties.[6] For example, nitroxoline inhibits [MetAP2](/source/METAP2) activity, an enzyme associated with [angiogenesis](/source/Angiogenesis), and [HUVEC](/source/HUVEC) proliferation.[7] This is further evidence that nitroxoline would make an effective anticancer drug. With different derivatives of nitroxoline demonstrating various levels of inhibition, nitroxoline may also prove to be a novel starting point for future research into cancer treatment.

## *Balamuthia* infection

In 2018, nitroxoline was identified via a [clinical metagenomic next-generation sequencing](/source/Clinical_metagenomic_next-generation_sequencing) analysis as a compound that could be [repurposed](/source/Drug_repurposing) as an [amoebicidal](/source/Amoebicidal) agent against *[Balamuthia mandrillaris](/source/Balamuthia_mandrillaris)* which causes the fatal disease [granulomatous amoebic encephalitis](/source/Granulomatous_amoebic_encephalitis) (GAE).[8]

In 2021, a patient survived an infection of *Balamuthia mandrillaris* after treatment with nitroxoline.[9][10] The man had been given the recommended drug therapy of [pentamidine](/source/Pentamidine), [sulfadiazine](/source/Sulfadiazine), [azithromycin](/source/Azithromycin), [fluconazole](/source/Fluconazole), [flucytosine](/source/Flucytosine), and [miltefosine](/source/Miltefosine) but progressed negatively. Therefore the regimen was complemented with nitroxoline which required the permission of the [FDA](/source/FDA) as the drug isn't approved in the United States. The cerebral lesion shrank only one week later after the new drug was added and the man later recovered.[11]

## References

1. **[^](#cite_ref-pmid7793877_1-0)** Pelletier C, Prognon P, Bourlioux P (March 1995). ["Roles of divalent cations and pH in mechanism of action of nitroxoline against Escherichia coli strains"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC162609). *Antimicrobial Agents and Chemotherapy*. **39** (3): 707–713. [doi](/source/Doi_(identifier)):[10.1128/aac.39.3.707](https://doi.org/10.1128%2Faac.39.3.707). [PMC](/source/PMC_(identifier)) [162609](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC162609). [PMID](/source/PMID_(identifier)) [7793877](https://pubmed.ncbi.nlm.nih.gov/7793877).

1. **[^](#cite_ref-2)** Sobke A, Klinger M, Hermann B, Sachse S, Nietzsche S, Makarewicz O, et al. (November 2012). ["The urinary antibiotic 5-nitro-8-hydroxyquinoline (Nitroxoline) reduces the formation and induces the dispersal of Pseudomonas aeruginosa biofilms by chelation of iron and zinc"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3486607). *Antimicrobial Agents and Chemotherapy*. **56** (11): 6021–6025. [doi](/source/Doi_(identifier)):[10.1128/aac.01484-12](https://doi.org/10.1128%2Faac.01484-12). [PMC](/source/PMC_(identifier)) [3486607](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3486607). [PMID](/source/PMID_(identifier)) [22926564](https://pubmed.ncbi.nlm.nih.gov/22926564).

1. **[^](#cite_ref-3)** Jiang H, Taggart JE, Zhang X, Benbrook DM, Lind SE, Ding WQ (December 2011). ["Nitroxoline (8-hydroxy-5-nitroquinoline) is more a potent anti-cancer agent than clioquinol (5-chloro-7-iodo-8-quinoline)"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395224). *Cancer Letters*. **312** (1): 11–17. [doi](/source/Doi_(identifier)):[10.1016/j.canlet.2011.06.032](https://doi.org/10.1016%2Fj.canlet.2011.06.032). [PMC](/source/PMC_(identifier)) [3395224](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395224). [PMID](/source/PMID_(identifier)) [21899946](https://pubmed.ncbi.nlm.nih.gov/21899946).

1. **[^](#cite_ref-4)** Mirković B, Renko M, Turk S, Sosič I, Jevnikar Z, Obermajer N, et al. (August 2011). "Novel mechanism of cathepsin B inhibition by antibiotic nitroxoline and related compounds". *ChemMedChem*. **6** (8): 1351–1356. [doi](/source/Doi_(identifier)):[10.1002/cmdc.201100098](https://doi.org/10.1002%2Fcmdc.201100098). [PMID](/source/PMID_(identifier)) [21598397](https://pubmed.ncbi.nlm.nih.gov/21598397). [S2CID](/source/S2CID_(identifier)) [2963633](https://api.semanticscholar.org/CorpusID:2963633).

1. **[^](#cite_ref-5)** Sosič I, Mirković B, Arenz K, Stefane B, Kos J, Gobec S (January 2013). "Development of new cathepsin B inhibitors: combining bioisosteric replacements and structure-based design to explore the structure-activity relationships of nitroxoline derivatives". *Journal of Medicinal Chemistry*. **56** (2): 521–533. [doi](/source/Doi_(identifier)):[10.1021/jm301544x](https://doi.org/10.1021%2Fjm301544x). [PMID](/source/PMID_(identifier)) [23252745](https://pubmed.ncbi.nlm.nih.gov/23252745).

1. **[^](#cite_ref-doi=10.1093/jnci/djq457_6-0)** Shim JS, Matsui Y, Bhat S, Nacev BA, Xu J, Bhang HE, et al. (December 2010). ["Effect of nitroxoline on angiogenesis and growth of human bladder cancer"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001967). *Journal of the National Cancer Institute*. **102** (24): 1855–1873. [doi](/source/Doi_(identifier)):[10.1093/jnci/djq457](https://doi.org/10.1093%2Fjnci%2Fdjq457). [PMC](/source/PMC_(identifier)) [3001967](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001967). [PMID](/source/PMID_(identifier)) [21088277](https://pubmed.ncbi.nlm.nih.gov/21088277).

1. **[^](#cite_ref-7)** Bhat S, Shim JS, Zhang F, Chong CR, Liu JO (April 2012). ["Substituted oxines inhibit endothelial cell proliferation and angiogenesis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767132). *Organic & Biomolecular Chemistry*. **10** (15): 2979–2992. [doi](/source/Doi_(identifier)):[10.1039/C2OB06978D](https://doi.org/10.1039%2FC2OB06978D). [PMC](/source/PMC_(identifier)) [3767132](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767132). [PMID](/source/PMID_(identifier)) [22391578](https://pubmed.ncbi.nlm.nih.gov/22391578).

1. **[^](#cite_ref-LaurieWhiteDeRisi2018_8-0)** Laurie MT, White CV, Retallack H, Wu W, Moser MS, Sakanari JA, et al. (October 2018). ["Functional Assessment of 2,177 U.S. and International Drugs Identifies the Quinoline Nitroxoline as a Potent Amoebicidal Agent against the Pathogen *Balamuthia mandrillaris*"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212833). *mBio*. **9** (5) e02051-18. [doi](/source/Doi_(identifier)):[10.1128/mBio.02051-18](https://doi.org/10.1128%2FmBio.02051-18). [PMC](/source/PMC_(identifier)) [6212833](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212833). [PMID](/source/PMID_(identifier)) [30377287](https://pubmed.ncbi.nlm.nih.gov/30377287).

1. **[^](#cite_ref-Nitroxoline_for_GAE2_9-0)** Kornei K (2023). "Repurposed drug battles 'brain-eating' amoeba". Science. [doi](/source/Doi_(identifier)):[10.1126/science.adh0048](https://doi.org/10.1126%2Fscience.adh0048).

1. **[^](#cite_ref-Spottiswoode_Nitroxoline2_10-0)** Spottiswoode N, Pet D, Kim A, Gruenberg K, Shah M, Ramachandran A, et al. (January 2023). ["Successful Treatment of Balamuthia mandrillaris Granulomatous Amebic Encephalitis with Nitroxoline"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9796214). *Emerging Infectious Diseases*. **29** (1): 197–201. [doi](/source/Doi_(identifier)):[10.3201/eid2901.221531](https://doi.org/10.3201%2Feid2901.221531). [PMC](/source/PMC_(identifier)) [9796214](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9796214). [PMID](/source/PMID_(identifier)) [36573629](https://pubmed.ncbi.nlm.nih.gov/36573629).

1. **[^](#cite_ref-11)** ["TWiP 222: Balamuthia in the brain with Natasha Spottiswoode"](https://www.microbe.tv/twip/twip-222/). 31 October 2023.

v t e Antibacterials: others (J01X, D06AX) Glycopeptides Lipoglycopeptides Avoparcin Corbomycin Dalbavancin Oritavancin Ristocetin Teicoplanin Telavancin Vancomycin Polymyxins Colistin Polymyxin B Steroid antibacterials Fusidic acid Imidazole derivatives Metronidazole Ornidazole Tinidazole Pleuromutilins Azamulin Lefamulin Retapamulin Tiamulin Valnemulin Nitrofuran derivatives Furaltadone Furazolidone Nifuroxazide Nifurtoinol Nifurzide Nitrofurantoin Nitrofurazone Other antibacterials Bacitracin Clofoctol Daptomycin Fosfomycin Gepotidacin Linezolid Mandelic acid Methenamine Nitroxoline Novobiocin Spectinomycin Tedizolid Xibornol Zoliflodacin

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Adapted from the Wikipedia article [Nitroxoline](https://en.wikipedia.org/wiki/Nitroxoline) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Nitroxoline?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.