DrugBank: Furazolidone (DB00614)

targets (1) enzymes (2)

Identification

Name

Furazolidone

Accession Number

DB00614 (APRD00988)

Type

small molecule

Groups

approved

Description

A nitrofuran derivative with antiprotozoal and antibacterial activity. Furazolidone binds bacterial DNA which leads to the gradual inhibition of monoamine oxidase. (From Martindale, The Extra Pharmacopoeia, 30th ed, p514)

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Nitrofurazolidone
Nitrofurazolidonum
USAF EA-1

Brand names

Bifuron
Corizium
Coryzium
Diafuron
Enterotoxon
Fiurox aerosol powder
Furall
Furaxon
Furaxone
Furazol
Furazolidine
Furazolidon
Furazon
Furidon
Furovag
Furox
Furoxal
Furoxane
Furoxon
Furoxone
Furoxone Liquid
Furoxone Swine Mix
Furozolidine
Giardil
Giarlam
Medaron
Neftin
Nicolen
Nifulidone
Nifuran
Nifurazolidone
Nitrofuroxon
Optazol
Ortazol
Puradin
Roptazol
Sclaventerol
Tikofuran
Topazone
Trichofuron
Tricofuron
Tricoron
Trifurox
Viofuragyn

Brand name mixtures

Not Available

Categories

Anti-Infective Agents, Local
Anti-Infective Agents, Urinary
Antitrichomonal Agents
Monoamine Oxidase Inhibitors

CAS number

67-45-8

Weight

Average: 225.1583
Monoisotopic: 225.038570349

Chemical Formula

C₈H₇N₃O₅

InChI Key

InChIKey=PLHJDBGFXBMTGZ-UHFFFAOYSA-N

InChI

InChI=1S/C8H7N3O5/c12-8-10(3-4-15-8)9-5-6-1-2-7(16-6)11(13)14/h1-2,5H,3-4H2

Plain Text

IUPAC Name

3-{[(5-nitrofuran-2-yl)methylidene]amino}-1,3-oxazolidin-2-one

SMILES

[O-][N+](=O)C1=CC=C(O1)C=NN1CCOC1=O

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Carbamates and Derivatives
Nitrofurans

Substructures

Carbamates and Derivatives
Oxoazaniums
Ethers
Nitro compounds
Nitrofurans
Heterocyclic compounds
Aromatic compounds
Hydrazine Derivatives
Furans
Imines
Oxazolidinones

Pharmacology

Indication

For the specific and symptomatic treatment of bacterial or protozoal diarrhea and enteritis caused by susceptible organisms.

Pharmacodynamics

Furoxone has a broad antibacterial spectrum covering the majority of gastrointestinal tract pathogens including E. coli, staphylococci, Salmonella, Shigella, Proteus, Aerobacter aerogenes, Vibrio cholerae and Giardia lamblia. Its bactericidal activity is based upon its interference with DNA replication and protein production; this antimicrobial action minimizes the development of resistant organisms.

Mechanism of action

Furazolidone and its related free radical products are believed to bind DNA and induce cross-links. Bacterial DNA is particularly susceptible to this drug leading to high levels of mutations (transitions and transversions) in the bacterial chromosome.

Absorption

Radiolabeled drug studies indicate that furazolidone is well absorbed following oral administration

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Furazolidone is rapidly and extensively metabolized; the primary metabolic pathway identified begins with nitro-reduction to the aminofuran derivative. Two major metabolites are produced: 3-amino-2-oxazolidone (AOZ) or beta-hydroxyethylhydrazine (HEH). AOZ is responsible for monoamine oxidase inhibition. Detoxification and elimination of the drug is done primarily by conjugation with glutathione.

Route of elimination

Not Available

Half life

10 minutes

Clearance

Not Available

Toxicity

Reactions to Furoxone have been reported including a fall in blood pressure, urticaria, fever, arthralgia, and a vesicular morbilliform rash. Other adverse effects can include a brown discoloration of the urine; hemolysis can occur in G6PDH-deficient patients. The drug has a monoamine oxidase (MAO) inhibitory effect and should never be given concurrently to individuals already taking MAO inhibitors.

Affected organisms

Microbes (bacteria, parasites)

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Shire development inc

Packagers

Professional Co.

Dosage forms

Form	Route	Strength
Liquid	Oral
Tablet	Oral

Prices

Unit description	Cost	Unit
Furazolidone powder	2.04 USD	g

Patents

Not Available

Properties

State

solid

Melting point

255 oC

Experimental Properties

Property	Value	Source
water solubility	40 mg/L	PhysProp
logP	0.9	PhysProp

Predicted Properties

Property	Value	Source
water solubility	3.64e-01 g/l	ALOGPS
logP	0.15	ALOGPS
logP	0.87	ChemAxon Molconvert
logS	-2.79	ALOGPS
pKa		ChemAxon Molconvert
hydrogen acceptor count	4	ChemAxon Molconvert
hydrogen donor count	0	ChemAxon Molconvert
polar surface area	100.86	ChemAxon Molconvert
rotatable bond count	3	ChemAxon Molconvert
refractivity	51.09	ChemAxon Molconvert
polarizability	19.74	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Drug	D00830
KEGG Compound	C07999
PubChem Compound	5323714
PubChem Substance	46507291
ChemSpider	3317
ChEBI	5195
ChEMBL	5195
Therapeutic Targets Database	DAP000993
PharmGKB	PA449718
Drug Product Database	674761
RxList	http://www.rxlist.com/cgi/generic2/furazol.htm
Drugs.com	http://www.drugs.com/cons/furazolidone.html
Wikipedia	http://en.wikipedia.org/wiki/Furazolidone

ATC Codes

G01AX06

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

show (74.1 KB)

Interactions

Drug Interactions

Not Available

Food Interactions

Not Available

Targets
1. DNA Pharmacological action: yes Actions: cross-linking/alkylation DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes. Gene Sequence: FASTA References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed 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 Meng J, Mangat SS, Grudzinski IP, Law FC: Evidence of 14C-furazolidone metabolite binding to the hepatic DNA of trout. Drug Metabol Drug Interact. 1998;14(4):209-19. Pubmed

Targets

1. DNA

Pharmacological action: yes
Actions: cross-linking/alkylation

DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.

Gene Sequence: FASTA

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
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
Meng J, Mangat SS, Grudzinski IP, Law FC: Evidence of 14C-furazolidone metabolite binding to the hepatic DNA of trout. Drug Metabol Drug Interact. 1998;14(4):209-19. Pubmed

Enzymes
1. Amine oxidase [flavin-containing] B Actions: inhibitor Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine UniProt ID: P27338 Gene: MAOB Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Timperio AM, Kuiper HA, Zolla L: Identification of a furazolidone metabolite responsible for the inhibition of amino oxidases. Xenobiotica. 2003 Feb;33(2):153-67. Pubmed Ali BH: Pharmacological, therapeutic and toxicological properties of furazolidone: some recent research. Vet Res Commun. 1999 Oct;23(6):343-60. Pubmed Hoogenboom LA, Tomassini O, Oorsprong MB, Kuiper HA: Use of pig hepatocytes to study the inhibition of monoamine oxidase by furazolidone. Food Chem Toxicol. 1991 Mar;29(3):185-91. Pubmed 2. Amine oxidase [flavin-containing] A Actions: inhibitor Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine UniProt ID: P21397 Gene: MAOA Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Timperio AM, Kuiper HA, Zolla L: Identification of a furazolidone metabolite responsible for the inhibition of amino oxidases. Xenobiotica. 2003 Feb;33(2):153-67. Pubmed Ali BH: Pharmacological, therapeutic and toxicological properties of furazolidone: some recent research. Vet Res Commun. 1999 Oct;23(6):343-60. Pubmed Hoogenboom LA, Tomassini O, Oorsprong MB, Kuiper HA: Use of pig hepatocytes to study the inhibition of monoamine oxidase by furazolidone. Food Chem Toxicol. 1991 Mar;29(3):185-91. Pubmed

Enzymes

1. Amine oxidase [flavin-containing] B

Actions: inhibitor

Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine

UniProt ID: P27338 Link_out

Gene: MAOB Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Timperio AM, Kuiper HA, Zolla L: Identification of a furazolidone metabolite responsible for the inhibition of amino oxidases. Xenobiotica. 2003 Feb;33(2):153-67. Pubmed
Ali BH: Pharmacological, therapeutic and toxicological properties of furazolidone: some recent research. Vet Res Commun. 1999 Oct;23(6):343-60. Pubmed
Hoogenboom LA, Tomassini O, Oorsprong MB, Kuiper HA: Use of pig hepatocytes to study the inhibition of monoamine oxidase by furazolidone. Food Chem Toxicol. 1991 Mar;29(3):185-91. Pubmed

2. Amine oxidase [flavin-containing] A

Actions: inhibitor

Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine

UniProt ID: P21397 Link_out

Gene: MAOA Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Timperio AM, Kuiper HA, Zolla L: Identification of a furazolidone metabolite responsible for the inhibition of amino oxidases. Xenobiotica. 2003 Feb;33(2):153-67. Pubmed
Ali BH: Pharmacological, therapeutic and toxicological properties of furazolidone: some recent research. Vet Res Commun. 1999 Oct;23(6):343-60. Pubmed
Hoogenboom LA, Tomassini O, Oorsprong MB, Kuiper HA: Use of pig hepatocytes to study the inhibition of monoamine oxidase by furazolidone. Food Chem Toxicol. 1991 Mar;29(3):185-91. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on August 10, 2011 15:07

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.