Identification

Name
Nitrofural
Accession Number
DB00336  (APRD00050)
Type
Small Molecule
Groups
Approved, Investigational, 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.

Structure
Thumb
Synonyms
  • 5-Nitro-2-furaldehyde semicarbazone
  • Furacilin
  • Nitrofural
International/Other Brands
Furacin / Furaderm / Nitrofurazone
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 treatment of bacterial skin infections including pyodermas, infected dermatoses and infections of cuts, wounds, burns and ulcers due to susceptible organisms.

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
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014480
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 — NitrofuralS01AX04 — NitrofuralS02AA02 — NitrofuralB05CA03 — NitrofuralD09AA03 — NitrofuralP01CC02 — Nitrofural
PDB Entries
1yki / 3r6w
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
  • Gallipot
  • Pharmedix
  • Taro Pharmaceuticals USA
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
Mass Spectrum (Electron Ionization)MSsplash10-0pb9-9500000000-c26d5be0126e0a0e8278
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

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]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 04:41