Nitrofural

Identification

Name
Nitrofural
Accession Number
DB00336  (APRD00050)
Type
Small Molecule
Groups
Approved, Vet Approved
Description

A topical anti-infective agent effective against gram-negative and gram-positive bacteria. It is used for superficial wounds, burns, ulcers, and skin infections. Nitrofurazone has also been administered orally in the treatment of trypanosomiasis. [PubChem]

Structure
Thumb
Synonyms
  • 5-Nitro-2-furaldehyde semicarbazone
  • Furacilin
  • Nitrofural
External IDs
Not Available
Product Ingredients
Not Available
Approved Prescription Products
Not Available
Approved Generic Prescription Products
Not Available
Approved Over the Counter Products
Not Available
Unapproved/Other Products
Not Available
International/Other Brands
Furacin / Furaderm / Nitrofurazone
Brand mixtures
Not Available
Categories
UNII
X8XI70B5Z6
CAS number
59-87-0
Weight
Average: 198.1362
Monoisotopic: 198.0389047
Chemical Formula
C6H6N4O4
InChI Key
IAIWVQXQOWNYOU-FPYGCLRLSA-N
InChI
InChI=1S/C6H6N4O4/c7-6(11)9-8-3-4-1-2-5(14-4)10(12)13/h1-3H,(H3,7,9,11)/b8-3+
IUPAC Name
[(E)-[(5-nitrofuran-2-yl)methylidene]amino]urea
SMILES
NC(=O)N\N=C\C1=CC=C(O1)[N+]([O-])=O

Pharmacology

Indication

For the treatement of bacterial skin infections including pyodermas, infected dermatoses and infections of cuts, wounds, burns and ulcers due to susceptible organisms.

Structured Indications
Not Available
Pharmacodynamics

Nitrofurazone is a topical antibacterial agent indicated as an adjunctive therapy for second and third degree burns when resistance to other agents is a real or potential problem. Nitrofurazone is also indicated in skin grafting when bacterial contamination may cause graft rejection or donor site infection, especially in hospitals with a history of resistant bacteria.

Mechanism of action

The exact mechanism of action is unknown. Nitrofurazone inhibits several bacterial enzymes, especially those involved in the aerobic and anaerobic degradation of glucose and pyruvate. This activity is believed also to affect pyruvate dehydrogenase, citrate synthetase, malate dehydrogenase, glutathione reductase, and pyruvate decarboxylase.

TargetActionsOrganism
APyruvate dehydrogenase [ubiquinone]
inhibitor
Escherichia coli (strain K12)
AGlutathione reductase
inhibitor
Escherichia coli (strain K12)
AMalate dehydrogenase
inhibitor
Escherichia coli (strain K12)
A[Citrate [pro-3S]-lyase] ligase
inhibitor
Escherichia coli (strain K12)
Absorption

Well absorbed.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Nitrofurans, including nitrofural, undergo metabolic reduction at the nitro group to generate reactive species which can covalently bind to cellular macromolecules (Polnaszek et al., 1984; Kutcher & McCalla, 1984; McCalla 1979; McCalla et al., 1975).

Route of elimination
Not Available
Half life

5 hours

Clearance
Not Available
Toxicity

Rat LD50 = 590 mg/kg; Allergic contact dermatitis is the most frequently reported adverse effect, occurring in approximately 1 % of patients treated.

Affected organisms
  • Gram negative and gram positive bacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Nitrofural can be increased when it is combined with Abiraterone.Approved
AmiodaroneThe metabolism of Nitrofural can be decreased when combined with Amiodarone.Approved, Investigational
ArtemetherThe metabolism of Nitrofural can be decreased when combined with Artemether.Approved
AtomoxetineThe metabolism of Nitrofural can be decreased when combined with Atomoxetine.Approved
BetaxololThe metabolism of Nitrofural can be decreased when combined with Betaxolol.Approved
BupropionThe metabolism of Nitrofural can be decreased when combined with Bupropion.Approved
CelecoxibThe metabolism of Nitrofural can be decreased when combined with Celecoxib.Approved, Investigational
ChloroquineThe metabolism of Nitrofural can be decreased when combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe metabolism of Nitrofural can be decreased when combined with Chlorpromazine.Approved, Vet Approved
CholecalciferolThe metabolism of Nitrofural can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Nitrofural can be decreased when combined with Cimetidine.Approved
CinacalcetThe metabolism of Nitrofural can be decreased when combined with Cinacalcet.Approved
CitalopramThe metabolism of Nitrofural can be decreased when combined with Citalopram.Approved
ClemastineThe metabolism of Nitrofural can be decreased when combined with Clemastine.Approved
ClobazamThe metabolism of Nitrofural can be decreased when combined with Clobazam.Approved, Illicit
ClomipramineThe metabolism of Nitrofural can be decreased when combined with Clomipramine.Approved, Vet Approved
ClotrimazoleThe metabolism of Nitrofural can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe metabolism of Nitrofural can be decreased when combined with Clozapine.Approved
CobicistatThe serum concentration of Nitrofural can be increased when it is combined with Cobicistat.Approved
CocaineThe metabolism of Nitrofural can be decreased when combined with Cocaine.Approved, Illicit
DarifenacinThe metabolism of Nitrofural can be decreased when combined with Darifenacin.Approved, Investigational
DarunavirThe serum concentration of Nitrofural can be increased when it is combined with Darunavir.Approved
DelavirdineThe metabolism of Nitrofural can be decreased when combined with Delavirdine.Approved
DesipramineThe metabolism of Nitrofural can be decreased when combined with Desipramine.Approved
DiphenhydramineThe metabolism of Nitrofural can be decreased when combined with Diphenhydramine.Approved
DronedaroneThe metabolism of Nitrofural can be decreased when combined with Dronedarone.Approved
DuloxetineThe metabolism of Nitrofural can be decreased when combined with Duloxetine.Approved
EliglustatThe metabolism of Nitrofural can be decreased when combined with Eliglustat.Approved
FluoxetineThe metabolism of Nitrofural can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvoxamineThe metabolism of Nitrofural can be decreased when combined with Fluvoxamine.Approved, Investigational
HaloperidolThe metabolism of Nitrofural can be decreased when combined with Haloperidol.Approved
ImipramineThe metabolism of Nitrofural can be decreased when combined with Imipramine.Approved
IndinavirThe metabolism of Nitrofural can be decreased when combined with Indinavir.Approved
IsoniazidThe metabolism of Nitrofural can be decreased when combined with Isoniazid.Approved
KetoconazoleThe metabolism of Nitrofural can be decreased when combined with Ketoconazole.Approved, Investigational
LopinavirThe metabolism of Nitrofural can be decreased when combined with Lopinavir.Approved
LorcaserinThe metabolism of Nitrofural can be decreased when combined with Lorcaserin.Approved
LumefantrineThe metabolism of Nitrofural can be decreased when combined with Lumefantrine.Approved
MethadoneThe metabolism of Nitrofural can be decreased when combined with Methadone.Approved
MethotrimeprazineThe metabolism of Nitrofural can be decreased when combined with Methotrimeprazine.Approved
MetoprololThe metabolism of Nitrofural can be decreased when combined with Metoprolol.Approved, Investigational
MirabegronThe metabolism of Nitrofural can be decreased when combined with Mirabegron.Approved
NevirapineThe metabolism of Nitrofural can be decreased when combined with Nevirapine.Approved
NicardipineThe metabolism of Nitrofural can be decreased when combined with Nicardipine.Approved
NilotinibThe metabolism of Nitrofural can be decreased when combined with Nilotinib.Approved, Investigational
PanobinostatThe serum concentration of Nitrofural can be increased when it is combined with Panobinostat.Approved, Investigational
ParoxetineThe metabolism of Nitrofural can be decreased when combined with Paroxetine.Approved, Investigational
Peginterferon alfa-2bThe serum concentration of Nitrofural can be decreased when it is combined with Peginterferon alfa-2b.Approved
PromazineThe metabolism of Nitrofural can be decreased when combined with Promazine.Approved, Vet Approved
QuinidineThe metabolism of Nitrofural can be decreased when combined with Quinidine.Approved
QuinineThe metabolism of Nitrofural can be decreased when combined with Quinine.Approved
RanolazineThe metabolism of Nitrofural can be decreased when combined with Ranolazine.Approved, Investigational
RitonavirThe metabolism of Nitrofural can be decreased when combined with Ritonavir.Approved, Investigational
RolapitantThe metabolism of Nitrofural can be decreased when combined with Rolapitant.Approved
RopiniroleThe metabolism of Nitrofural can be decreased when combined with Ropinirole.Approved, Investigational
SertralineThe metabolism of Nitrofural can be decreased when combined with Sertraline.Approved
StiripentolThe metabolism of Nitrofural can be decreased when combined with Stiripentol.Approved
TerbinafineThe metabolism of Nitrofural can be decreased when combined with Terbinafine.Approved, Investigational, Vet Approved
ThioridazineThe metabolism of Nitrofural can be decreased when combined with Thioridazine.Withdrawn
TiclopidineThe metabolism of Nitrofural can be decreased when combined with Ticlopidine.Approved
TipranavirThe metabolism of Nitrofural can be decreased when combined with Tipranavir.Approved, Investigational
TranylcypromineThe metabolism of Nitrofural can be decreased when combined with Tranylcypromine.Approved
VenlafaxineThe metabolism of Nitrofural can be decreased when combined with Venlafaxine.Approved
ZiprasidoneThe metabolism of Nitrofural can be decreased when combined with Ziprasidone.Approved
Food Interactions
Not Available

References

Synthesis Reference
Not Available
General References
Not Available
External Links
Human Metabolome Database
HMDB14480
KEGG Drug
D00862
KEGG Compound
C08042
PubChem Compound
5447130
PubChem Substance
46506509
ChemSpider
4566720
ChEMBL
CHEMBL869
PharmGKB
PA164754877
HET
NFZ
Drugs.com
Drugs.com Drug Page
Wikipedia
Nitrofurazone
ATC Codes
D08AF01 — NitrofuralS02AA02 — NitrofuralS01AX04 — NitrofuralB05CA03 — NitrofuralD09AA03 — NitrofuralP01CC02 — Nitrofural
AHFS Codes
  • 08:36.00
  • 40:28.08
PDB Entries
Not Available
FDA label
Not Available
MSDS
Download (73.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1

Pharmacoeconomics

Manufacturers
  • Shire development inc
  • Sherwood medical co
  • Ambix laboratories div organics corp america
  • Lannett co inc
  • Perrigo new york inc
  • Taro pharmaceuticals usa inc
  • Wendt laboratories inc
Packagers
Dosage forms
Not Available
Prices
Unit descriptionCostUnit
Nitrofurazone powder0.63USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)238 dec °CPhysProp
water solubility210 mg/L (at 25 °C)BEILSTEIN
logP0.23HANSCH,C ET AL. (1995)
pKa10SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.268 mg/mLALOGPS
logP0.23ALOGPS
logP-0.14ChemAxon
logS-2.9ALOGPS
pKa (Strongest Acidic)11.79ChemAxon
pKa (Strongest Basic)-2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area126.44 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity45.21 m3·mol-1ChemAxon
Polarizability16.92 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.5716
Blood Brain Barrier+0.9214
Caco-2 permeable-0.5694
P-glycoprotein substrateNon-substrate0.7552
P-glycoprotein inhibitor INon-inhibitor0.9271
P-glycoprotein inhibitor IINon-inhibitor0.9278
Renal organic cation transporterNon-inhibitor0.9347
CYP450 2C9 substrateNon-substrate0.769
CYP450 2D6 substrateNon-substrate0.8326
CYP450 3A4 substrateNon-substrate0.6211
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9379
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8418
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9287
Ames testAMES toxic0.9234
CarcinogenicityNon-carcinogens0.692
BiodegradationNot ready biodegradable0.7708
Rat acute toxicity2.5276 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9188
hERG inhibition (predictor II)Non-inhibitor0.9311
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )

Spectra

Mass Spec (NIST)
Download (8.69 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted LC-MS/MS Spectrum - 10V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 20V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 40V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 10V, NegativePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 20V, NegativePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 40V, NegativePredicted LC-MS/MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0pb9-9500000000-c26d5be0126e0a0e8278

Taxonomy

Description
This compound belongs to the class of organic compounds known as nitrofurans. These are compounds containing a furan ring which bears a nitro group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Furans
Sub Class
Nitrofurans
Direct Parent
Nitrofurans
Alternative Parents
Nitroaromatic compounds / Semicarbazones / Heteroaromatic compounds / Organic carbonic acids and derivatives / Propargyl-type 1,3-dipolar organic compounds / Oxacyclic compounds / Organic oxoazanium compounds / Organopnictogen compounds / Organic zwitterions / Organic oxides
show 2 more
Substituents
Nitroaromatic compound / 2-nitrofuran / Semicarbazone / Semicarbazide / Heteroaromatic compound / C-nitro compound / Carbonic acid derivative / Organic nitro compound / Organic oxoazanium / Allyl-type 1,3-dipolar organic compound
show 13 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Thiamine pyrophosphate binding
Specific Function
Not Available
Gene Name
poxB
Uniprot ID
P07003
Uniprot Name
Pyruvate dehydrogenase [ubiquinone]
Molecular Weight
62010.845 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Nadp binding
Specific Function
Maintains high levels of reduced glutathione in the cytosol.
Gene Name
gor
Uniprot ID
P06715
Uniprot Name
Glutathione reductase
Molecular Weight
48772.195 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Vega-Teijido M, Caracelli I, Zukerman-Schpector J: Conformational analyses and docking studies of a series of 5-nitrofuran- and 5-nitrothiophen-semicarbazone derivatives in three possible binding sites of trypanothione and glutathione reductases. J Mol Graph Model. 2006 Mar;24(5):349-55. Epub 2005 Nov 7. [PubMed:16275032 ]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Oxidoreductase activity
Specific Function
Catalyzes the reversible oxidation of malate to oxaloacetate.
Gene Name
mdh
Uniprot ID
P61889
Uniprot Name
Malate dehydrogenase
Molecular Weight
32337.065 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
N-acetyltransferase activity
Specific Function
Acetylation of prosthetic group (2-(5''-phosphoribosyl)-3'-dephosphocoenzyme-A) of the gamma subunit of citrate lyase.
Gene Name
citC
Uniprot ID
P77390
Uniprot Name
[Citrate [pro-3S]-lyase] ligase
Molecular Weight
40076.805 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xanthine oxidase activity
Specific Function
Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Ha...
Gene Name
XDH
Uniprot ID
P47989
Uniprot Name
Xanthine dehydrogenase/oxidase
Molecular Weight
146422.99 Da
References
  1. Tatsumi K, Kitamura S, Yoshimura H: Reduction of nitrofuran derivatives by xanthine oxidase and microsomes. Isolation and identification of reduction products. Arch Biochem Biophys. 1976 Jul;175(1):131-7. [PubMed:952514 ]
  2. Kutcher WW, McCalla DR: Aerobic reduction of 5-nitro-2-furaldehyde semicarbazone by rat liver xanthine dehydrogenase. Biochem Pharmacol. 1984 Mar 1;33(5):799-805. [PubMed:6585203 ]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Drug created on June 13, 2005 07:24 / Updated on September 01, 2017 10:26