T3DB: Metronidazole

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Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (1)XML

Targets (1)

Record Information

Version

2.0

Creation Date

2014-09-11 02:05:41 UTC

Update Date

2014-12-24 20:26:55 UTC

Accession Number

T3D4703

Identification

Common Name

Metronidazole

Class

Small Molecule

Description

A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985) this substance may reasonably be anticipated to be a carcinogen.

Compound Type

Amine
Anti-Infective Agent
Antiprotozoal Agent
Drug
Household Toxin
Metabolite
Organic Compound
Radiation-Sensitizing Agent
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
1-(2-hydroxy-1-ethyl)-2-methyl-5-nitroimidazole
1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole
1-(beta-Ethylol)-2-methyl-5-nitro-3-azapyrrole
1-(beta-Hydroxyethyl)-2-methyl-5-nitroimidazole
1-(beta-Oxyethyl)-2-methyl-5-nitroimidazole
1-(β-ethylol)-2-methyl-5-nitro-3-azapyrrole
1-(β-hydroxyethyl)-2-methyl-5-nitroimidazole
1-(β-oxyethyl)-2-methyl-5-nitroimidazole
2-methyl-1-(2-hydroxyethyl)-5-nitroimidazole
2-methyl-3-(2-hydroxyethyl)-4-nitroimidazole
2-methyl-5-nitroimidazole-1-ethanol
Acromona
Anabact
Arilin
Clont
Deflamon
Efloran
Elyzol
Entizol
Flagyl
Fossyol
Klion
Klont
Methronidazole
MetroCream
Metrogel
Metrogel-Vaginal
MetroLotion
Metrolyl
Metronidazol
Metronidazole Benzoate
Metronidazole in Plastic Container
Metronidazolo
Metronidazolum
Metrotop
Nalox
Nidagel
Noritate
Novonidazol
Orvagil
Protostat
Rosadan
Takimetol
Trichazole
Trichex
Trichopol
Tricowas B
Trikacide
Trikozol
Vagilen
Vagimid
Vandazole
Vertisal
Zadstat

Chemical Formula

C₆H₉N₃O₃

Average Molecular Mass

171.154 g/mol

Monoisotopic Mass

171.064 g/mol

CAS Registry Number

443-48-1

IUPAC Name

2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethan-1-ol

Traditional Name

metronidazole

SMILES

CC1=NC=C(N1CCO)N(=O)=O

InChI Identifier

InChI=1S/C6H9N3O3/c1-5-7-4-6(9(11)12)8(5)2-3-10/h4,10H,2-3H2,1H3

InChI Key

InChIKey=VAOCPAMSLUNLGC-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as nitroimidazoles. Nitroimidazoles are compounds containing an imidazole ring which bears a nitro group.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Azoles

Sub Class

Imidazoles

Direct Parent

Nitroimidazoles

Alternative Parents

Substituents

1,2,5-trisubstituted-imidazole
Nitroaromatic compound
Nitroimidazole
Trisubstituted imidazole
N-substituted imidazole
Heteroaromatic compound
Organic nitro compound
C-nitro compound
Alkanolamine
Azacycle
Organic 1,3-dipolar compound
Propargyl-type 1,3-dipolar organic compound
Allyl-type 1,3-dipolar organic compound
Organic oxoazanium
Hydrocarbon derivative
Primary alcohol
Organooxygen compound
Organonitrogen compound
Organic oxide
Organopnictogen compound
Organic zwitterion
Organic oxygen compound
Organic nitrogen compound
Alcohol
Aromatic heteromonocyclic compound

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

C-nitro compound (CHEBI:6909 )
imidazoles (CHEBI:6909 )
primary alcohol (CHEBI:6909 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	160.5°C
Boiling Point	Not Available
Solubility	9500 mg/L (at 25°C)
LogP	-0.02

Predicted Properties

Property	Value	Source
Water Solubility	5.92 g/L	ALOGPS
logP	-0.15	ALOGPS
logP	-0.46	ChemAxon
logS	-1.5	ALOGPS
pKa (Strongest Acidic)	15.42	ChemAxon
pKa (Strongest Basic)	2.57	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	81.19 Å²	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	40.22 m³·mol⁻¹	ChemAxon
Polarizability	15.87 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0udl-9700000000-f1b60dcdd221dbdf9eaa	JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-0fmi-9410000000-3cec2097481329b98054	JSpectraViewer
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	JSpectraViewer
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-004i-1900000000-659f2bbb83f8ef5a85d1	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-004i-0900000000-50c7cfe79eb17c4440a8	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-00di-0900000000-b06d808767cc01c0d494	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-00fr-0900000000-e9c07cc448b8fb519022	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-004i-0900000000-8ad03b44aa7557127e34	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-004i-0900000000-ed7ba5c872a6309a31d4	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-004i-2900000000-e0ead4b0eec72b9c44b6	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-004i-5900000000-2da8a7b45537f9063220	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-00di-0900000000-24d94f1704e577b05eb7	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-00fr-0900000000-fbb1c4e8457cd3d799b9	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-004i-0900000000-fd6166313a17f944f530	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-004i-0900000000-5ebb32a580e1f5d00170	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-004i-2900000000-811a6e7e45b7ea1a6184	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-004i-5900000000-082e6de6c0fa3f382d84	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-004i-0900000000-baf9e195c01d875e77b5	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-00di-0900000000-ec181c008a10dac8040b	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-004i-1900000000-2a218e19a8fadb9c66d6	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-003r-9500000000-ed02acd36b190c189cc9	JSpectraViewer \| MoNA
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-001i-9000000000-71ea79659ccd75c64bef	JSpectraViewer \| MoNA
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-00di-0900000000-b28839ace139ee8a385b	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-01ox-0900000000-94e5ccc473c03e521e89	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-01po-9500000000-64f688b22d9371ed56c1	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-00di-0900000000-5f65f2637682eccd62a2	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-05fu-3900000000-dbc213039f9c3a43948e	JSpectraViewer
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0007-9300000000-935f6b6b00b1b6b723b5	JSpectraViewer
MS	Mass Spectrum (Electron Ionization)	splash10-0ul0-9300000000-2268b08f47fed3f6d263	JSpectraViewer \| MoNA
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer
1D NMR	13C NMR Spectrum	Not Available	JSpectraViewer
1D NMR	1H NMR Spectrum	Not Available	JSpectraViewer

Toxicity Profile

Route of Exposure

Well absorbed (at least 80%) with peak plasma concentrations achieved in 1-3 hours following oral administration of therapeutic doses of immediate release formulation.

Mechanism of Toxicity

Metronidazole is a prodrug. Unionized metronidazole is selective for anaerobic bacteria due to their ability to intracellularly reduce metronidazole to its active form. This reduced metronidazole then covalently binds to DNA, disrupt its helical structure, inhibiting bacterial nucleic acid synthesis and resulting in bacterial cell death.

Metabolism

Hepatic metabolism by hydroxylation, oxidation, and glucuronidation. Half Life: 6-8 hours

Toxicity Values

LD50=500 mg/kg/day (orally in rat).

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

2B, possibly carcinogenic to humans. (5)

Uses/Sources

For the treatment of anaerobic infections and mixed infections, surgical prophylaxis requiring anaerobic coverage, Clostridium difficile-associated diarrhea and colitis, Helicobacter pylori infection and duodenal ulcer disease, bacterial vaginosis, Giardia lamblia gastro-enteritis, amebiasis caused by Entamoeba histolytica, acne rosacea (topical treatment), and Trichomonas infections.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Adverse effects include reversible peripheral neuropathy with prolonged therapy, CNS toxicity, disulfiram effect with alcohol, dark red-brown urine, metallic taste, nausea, epigastric distress, dizziness, vertigo and paresthesias associated with high doses, and neutropenia (reversible and mild).

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

6909

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

2MN

ACToR ID

Not Available

Wikipedia Link

Metronidazole

References

Synthesis Reference

DrugSyn.org

MSDS

Link

General References

Shennan A, Crawshaw S, Briley A, Hawken J, Seed P, Jones G, Poston L: A randomised controlled trial of metronidazole for the prevention of preterm birth in women positive for cervicovaginal fetal fibronectin: the PREMET Study. BJOG. 2006 Jan;113(1):65-74. [16398774 ]
Lamont RF: Can antibiotics prevent preterm birth--the pro and con debate. BJOG. 2005 Mar;112 Suppl 1:67-73. [15715599 ]
Williams CS, Woodcock KR: Do ethanol and metronidazole interact to produce a disulfiram-like reaction? Ann Pharmacother. 2000 Feb;34(2):255-7. [10676835 ]
Visapaa JP, Tillonen JS, Kaihovaara PS, Salaspuro MP: Lack of disulfiram-like reaction with metronidazole and ethanol. Ann Pharmacother. 2002 Jun;36(6):971-4. [12022894 ]
International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

1. DNA

General Function:: Used for biological information storage.
Specific Function:: DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:: 2.15 x 10¹² Da

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
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. [17016423 ]
Salles JM, Salles MJ, Moraes LA, Silva MC: Invasive amebiasis: an update on diagnosis and management. Expert Rev Anti Infect Ther. 2007 Oct;5(5):893-901. [17914922 ]
Li AQ, Dai N, Yan J, Zhu YL: [Screening for metronidazole-resistance associated gene fragments of Helicobacter pylori by suppression subtractive hybridization]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2007 Sep;36(5):465-9. [17924465 ]
Edwards DI: Nitroimidazole drugs--action and resistance mechanisms. I. Mechanisms of action. J Antimicrob Chemother. 1993 Jan;31(1):9-20. [8444678 ]

Metronidazole (T3D4703)

Structure for T3D4703: Metronidazole

Targets

References