Identification

Name
Nitroxoline
Accession Number
DB01422
Type
Small Molecule
Groups
Approved
Description

Nitroxoline is a urinary antibacterial agent active against susceptible gram-positive and gram-negative organisms commonly found in urinary tract infections. It is a fluorquinolone that is active against bacterial gyrases.

Structure
Thumb
Synonyms
  • 5-Nitro-8-hydroxyquinoline
  • 5-Nitro-8-oxyquinoline
  • 5-Nitro-8-quinolinol
  • 5-Nitrox
  • 5-NOK
  • 5NOK
  • 8-Hydroxy-5-nitroquinoline
  • Nitroxolina
  • Nitroxolinum
External IDs
A-82
International/Other Brands
Nitroxoline
Categories
UNII
A8M33244M6
CAS number
4008-48-4
Weight
Average: 190.1555
Monoisotopic: 190.037842068
Chemical Formula
C9H6N2O3
InChI Key
RJIWZDNTCBHXAL-UHFFFAOYSA-N
InChI
InChI=1S/C9H6N2O3/c12-8-4-3-7(11(13)14)6-2-1-5-10-9(6)8/h1-5,12H
IUPAC Name
5-nitroquinolin-8-ol
SMILES
OC1=C2N=CC=CC2=C(C=C1)[N+]([O-])=O

Pharmacology

Indication

Nitroxoline is an antibiotic agent.

Pharmacodynamics
Not Available
Mechanism of action

This drug may also have antitumor activity by inhibition of type 2 methionine aminopeptidase (MetAP2) protein which is involved in angiogenesis. Its antibacterial activity may stem from the metal ion complexation vital for bacterial growth.

TargetActionsOrganism
AMethionine aminopeptidase 2
inhibitor
Human
UMagnesium cation
chelator
Human
UManganese cation
chelator
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
Amphotericin BThe therapeutic efficacy of Amphotericin B can be decreased when used in combination with Nitroxoline.
AmrinoneThe therapeutic efficacy of Nitroxoline can be increased when used in combination with Amrinone.
AzimilideThe therapeutic efficacy of Nitroxoline can be increased when used in combination with Azimilide.
BuspironeThe metabolism of Buspirone can be decreased when combined with Nitroxoline.
BusulfanThe serum concentration of Busulfan can be increased when it is combined with Nitroxoline.
CisaprideThe serum concentration of Cisapride can be increased when it is combined with Nitroxoline.
DidanosineDidanosine can cause a decrease in the absorption of Nitroxoline resulting in a reduced serum concentration and potentially a decrease in efficacy.
DocetaxelThe metabolism of Docetaxel can be decreased when combined with Nitroxoline.
EtravirineThe serum concentration of Etravirine can be increased when it is combined with Nitroxoline.
FosphenytoinThe serum concentration of Nitroxoline can be decreased when it is combined with Fosphenytoin.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015491
PubChem Compound
19910
PubChem Substance
46505497
ChemSpider
18756
BindingDB
64987
ChEBI
67121
ChEMBL
CHEMBL1454910
PharmGKB
PA164754993
HET
HNQ
Wikipedia
Nitroxoline
ATC Codes
J01XX07 — Nitroxoline
PDB Entries
3ai8 / 5y1y

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)180 °CPhysProp
logP1.99HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility2.73 mg/mLALOGPS
logP1.9ALOGPS
logP1.77ChemAxon
logS-1.8ALOGPS
pKa (Strongest Acidic)6.88ChemAxon
pKa (Strongest Basic)2.08ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area78.94 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity49.28 m3·mol-1ChemAxon
Polarizability17.16 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9903
Blood Brain Barrier+0.8359
Caco-2 permeable+0.5318
P-glycoprotein substrateNon-substrate0.7501
P-glycoprotein inhibitor INon-inhibitor0.8255
P-glycoprotein inhibitor IINon-inhibitor0.7717
Renal organic cation transporterNon-inhibitor0.8555
CYP450 2C9 substrateNon-substrate0.7446
CYP450 2D6 substrateNon-substrate0.8236
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateInhibitor0.514
CYP450 2C9 inhibitorNon-inhibitor0.5166
CYP450 2D6 inhibitorNon-inhibitor0.7747
CYP450 2C19 inhibitorNon-inhibitor0.519
CYP450 3A4 inhibitorNon-inhibitor0.7765
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5604
Ames testAMES toxic0.9492
CarcinogenicityNon-carcinogens0.7562
BiodegradationNot ready biodegradable0.9907
Rat acute toxicity2.6189 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7788
hERG inhibition (predictor II)Non-inhibitor0.8267
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (8.15 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-002b-3900000000-cf44cf477f74a379b18a

Taxonomy

Description
This compound belongs to the class of organic compounds known as nitroquinolines and derivatives. These are compounds containing a nitro group attached to a quinoline moiety.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Quinolines and derivatives
Sub Class
Nitroquinolines and derivatives
Direct Parent
Nitroquinolines and derivatives
Alternative Parents
8-hydroxyquinolines / Nitroaromatic compounds / 1-hydroxy-2-unsubstituted benzenoids / Pyridines and derivatives / Heteroaromatic compounds / Propargyl-type 1,3-dipolar organic compounds / Organic oxoazanium compounds / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds
show 4 more
Substituents
Nitroquinoline / 8-hydroxyquinoline / Nitroaromatic compound / 1-hydroxy-2-unsubstituted benzenoid / Pyridine / Benzenoid / Heteroaromatic compound / C-nitro compound / Organic nitro compound / Organic oxoazanium
show 13 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
C-nitro compound, monohydroxyquinoline (CHEBI:67121)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Poly(a) rna binding
Specific Function
Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala...
Gene Name
METAP2
Uniprot ID
P50579
Uniprot Name
Methionine aminopeptidase 2
Molecular Weight
52891.145 Da
References
  1. Shim JS, Matsui Y, Bhat S, Nacev BA, Xu J, Bhang HE, Dhara S, Han KC, Chong CR, Pomper MG, So A, Liu JO: Effect of nitroxoline on angiogenesis and growth of human bladder cancer. J Natl Cancer Inst. 2010 Dec 15;102(24):1855-73. doi: 10.1093/jnci/djq457. Epub 2010 Nov 18. [PubMed:21088277]
2. Magnesium cation
Kind
Small molecule
Organism
Human
Pharmacological action
Unknown
Actions
Chelator
References
  1. Pelletier C, Prognon P, Latrache H, Villart L, Bourlioux P: [Microbiological consequences of chelation of bivalent metal cations by nitroxoline]. Pathol Biol (Paris). 1994 May;42(5):406-11. [PubMed:7824304]
  2. Pelletier C, Prognon P, Bourlioux P: Roles of divalent cations and pH in mechanism of action of nitroxoline against Escherichia coli strains. Antimicrob Agents Chemother. 1995 Mar;39(3):707-13. [PubMed:7793877]
3. Manganese cation
Kind
Small molecule
Organism
Human
Pharmacological action
Unknown
Actions
Chelator
References
  1. Pelletier C, Prognon P, Latrache H, Villart L, Bourlioux P: [Microbiological consequences of chelation of bivalent metal cations by nitroxoline]. Pathol Biol (Paris). 1994 May;42(5):406-11. [PubMed:7824304]
  2. Pelletier C, Prognon P, Bourlioux P: Roles of divalent cations and pH in mechanism of action of nitroxoline against Escherichia coli strains. Antimicrob Agents Chemother. 1995 Mar;39(3):707-13. [PubMed:7793877]

Drug created on July 24, 2007 05:15 / Updated on August 02, 2018 04:36