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Flucytosine (T3D2983)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (2)XML
Targets (2)
Record Information
Version2.0
Creation Date2009-07-21 20:28:21 UTC
Update Date2014-12-24 20:25:54 UTC
Accession NumberT3D2983
Identification
Common NameFlucytosine
ClassSmall Molecule
DescriptionFlucytosine is only found in individuals that have used or taken this drug. It is a fluorinated cytosine analog that is used as an antifungal agent. [PubChem]Although the exact mode of action is unknown, it has been proposed that flucytosine acts directly on fungal organisms by competitive inhibition of purine and pyrimidine uptake and indirectly by intracellular metabolism to 5-fluorouracil. Flucytosine enters the fungal cell via cytosine permease; thus, flucytosine is metabolized to 5-fluorouracil within fungal organisms. The 5-fluorouracil is extensively incorporated into fungal RNA and inhibits synthesis of both DNA and RNA. The result is unbalanced growth and death of the fungal organism. It also appears to be an inhibitor of fungal thymidylate synthase.
Compound Type
  • Amine
  • Antifungal Agent
  • Antimetabolite
  • Drug
  • Metabolite
  • Organic Compound
  • Organofluoride
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
5-FC
5-Fluorocystosine
5-Fluorocytosin
5-Fluorocytosine
5-Flurocytosine
Ancobon
Ancotil
Flucytosin
Fluocytosine
Fluorcytosine
Flusine
Chemical FormulaC4H4FN3O
Average Molecular Mass129.093 g/mol
Monoisotopic Mass129.034 g/mol
CAS Registry Number2022-85-7
IUPAC Name6-amino-5-fluoro-1,2-dihydropyrimidin-2-one
Traditional Nameflucytosine
SMILESOC1=NC=C(F)C(=N)N1
InChI IdentifierInChI=1S/C4H4FN3O/c5-2-1-7-4(9)8-3(2)6/h1H,(H3,6,7,8,9)
InChI KeyInChIKey=XRECTZIEBJDKEO-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as halopyrimidines. These are aromatic compounds containing a halogen atom linked to a pyrimidine ring. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazines
Sub ClassPyrimidines and pyrimidine derivatives
Direct ParentHalopyrimidines
Alternative Parents
Substituents
  • Aminopyrimidine
  • Halopyrimidine
  • Pyrimidone
  • Aryl fluoride
  • Aryl halide
  • Hydropyrimidine
  • Heteroaromatic compound
  • Azacycle
  • Amine
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point296°C
Boiling PointNot Available
Solubility1.5E+004 mg/L (at 25°C)
LogP-1.1
Predicted Properties
PropertyValueSource
Water Solubility1.92 g/LALOGPS
logP-0.24ALOGPS
logP-0.95ChemAxon
logS-1.8ALOGPS
pKa (Strongest Acidic)8.16ChemAxon
pKa (Strongest Basic)1.06ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area67.48 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity38.22 m³·mol⁻¹ChemAxon
Polarizability9.97 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-004i-5900000000-62cd06162d248f459f77View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-002r-9400000000-acd1b588a4052f6fc2ddView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-002r-9400000000-a4e7dd3c4c886861c0eaView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-000i-9200000000-b3fb9cad9c2b375b08c6View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-000i-9100000000-11fb61e55faa71878d87View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-000i-9000000000-13935b6ab4a3d8adaa08View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-000i-9000000000-cd981efe159dd44555f4View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-001i-0900000000-a228aa7f5ecaf516455fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-001i-0900000000-ec5b7f7d9f3c75649dc2View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-03e9-0900000000-15df2a7b685c4dd4ca17View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-001i-0900000000-7110f8accb80c700a2a5View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-001i-0900000000-89290e0501d587938afbView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-001i-0900000000-7248b6df062077397b61View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-001i-1900000000-df83e87e1bcbc8311be6View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-01q9-3900000000-42649a5ceee8a4619fc3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-08gr-9800000000-8cb7a586d34dd7913561View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-0900000000-3daf46ab201d0847e716View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-4900000000-08676c044da012e58509View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0007-9000000000-fc78e7fb18ada3e97d98View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-2900000000-d0b2503a7f5865ac1efdView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00nu-9100000000-ee11917ba44963a8210bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-e5c5889e9b5cd0c8cae9View in MoNA
Toxicity Profile
Route of ExposureRapidly and virtually completely absorbed following oral administration. Bioavailability 78% to 89%.
Mechanism of ToxicityAlthough the exact mode of action is unknown, it has been proposed that flucytosine acts directly on fungal organisms by competitive inhibition of purine and pyrimidine uptake and indirectly by intracellular metabolism to 5-fluorouracil. Flucytosine enters the fungal cell via cytosine permease; thus, flucytosine is metabolized to 5-fluorouracil within fungal organisms. The 5-fluorouracil is extensively incorporated into fungal RNA and inhibits synthesis of both DNA and RNA. The result is unbalanced growth and death of the fungal organism. It also appears to be an inhibitor of fungal thymidylate synthase.
MetabolismFlucytosine is deaminated, possibly by gut bacteria or by the fungal targets, to 5-fluorouracil, the active metabolite. Route of Elimination: Flucytosine is excreted via the kidneys by means of glomerular filtration without significant tubular reabsorption. A small portion of the dose is excreted in the feces. Half Life: 2.4 to 4.8 hours.
Toxicity ValuesLD50: 15 gm/kg (Oral, Rat) (1)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment (in combination with amphotericin B) of serious infections caused by susceptible strains of Candida (septicemia, endocarditis and urinary system infections) and/or Cryptococcus (meningitis and pulmonary infections).
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentIn the management of overdosage, prompt gastric lavage or the use of an emetic is recommended. Adequate fluid intake should be maintained, by the intravenous route if necessary, since Ancobon is excreted unchanged via the renal tract. The hematologic parameters should be monitored frequently; liver and kidney function should be carefully monitored. Should any abnormalities appear in any of these parameters, appropriate therapeutic measures should be instituted. Since hemodialysis has been shown to rapidly reduce serum concentrations in anuric patients, this method may be considered in the management of overdosage. (5)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01099
HMDB IDHMDB15231
PubChem Compound ID3366
ChEMBL IDCHEMBL1463
ChemSpider ID3249
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID5100
BioCyc IDNot Available
CTD IDNot Available
Stitch IDFlucytosine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkFlucytosine
References
Synthesis Reference

Bernd Baasner, Erich Klauke, “Process for the preparation of 5-fluorocytosine.” U.S. Patent US4703121, issued September, 1961.

MSDSLink
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Bertout S, Dunyach C, Drakulovski P, Reynes J, Mallie M: Comparison of the Sensititre YeastOne(R) dilution method with the Clinical Laboratory Standards Institute (CLSI) M27-A3 microbroth dilution reference method for determining MIC of eight antifungal agents on 102 yeast strains. Pathol Biol (Paris). 2011 Feb;59(1):48-51. doi: 10.1016/j.patbio.2010.07.020. Epub 2010 Sep 16. [20843616 ]
  3. Kaouech E, Kallel K, Belhadj S, Anane S, Ben Chaabane T, Ben Fadhl K, Khedher A, Meddeb B, Ben Lakhal S, Chaker E: [Twenty-two cases of neuromeningeal cryptococcosis in Tunisia]. Med Mal Infect. 2009 Dec;39(12):914-9. doi: 10.1016/j.medmal.2009.02.004. Epub 2009 Apr 8. [19359114 ]
  4. Park BJ, Park JC, Taguchi H, Fukushima K, Hyon SH, Takatori K: Antifungal susceptibility of epigallocatechin 3-O-gallate (EGCg) on clinical isolates of pathogenic yeasts. Biochem Biophys Res Commun. 2006 Aug 25;347(2):401-5. Epub 2006 Jun 15. [16831406 ]
  5. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot 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
  1. Osterman DG, DePillis GD, Wu JC, Matsuda A, Santi DV: 5-Fluorocytosine in DNA is a mechanism-based inhibitor of HhaI methylase. Biochemistry. 1988 Jul 12;27(14):5204-10. [3167042 ]
  2. Waldorf AR, Polak A: Mechanisms of action of 5-fluorocytosine. Antimicrob Agents Chemother. 1983 Jan;23(1):79-85. [6338821 ]
  3. Wyszynski MW, Gabbara S, Kubareva EA, Romanova EA, Oretskaya TS, Gromova ES, Shabarova ZA, Bhagwat AS: The cysteine conserved among DNA cytosine methylases is required for methyl transfer, but not for specific DNA binding. Nucleic Acids Res. 1993 Jan 25;21(2):295-301. [8441637 ]
Target Details
2. DNA (cytosine-5)-methyltransferase 1
General Function:
Zinc ion binding
Specific Function:
Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9.
Gene Name:
DNMT1
Uniprot ID:
P26358
Molecular Weight:
183163.635 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]