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Flucytosine

July 24, 2017
Common Name

Flucytosine Description

Flucytosine 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 intracellliar 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 reslit is unbalanced growth and death of the fungal organism. It also appears to be an inhibitor of fungal thymidylate synthase. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source 5-FCChEBI 5-FluorocystosineChEBI 5-FluorocytosineChEBI AncobonChEBI AncotilChEBI FlucytosinaChEBI FlucytosinumChEBI 5-FluorocytosinHMDB 5-FlurocytosineHMDB FlucytosinHMDB FluocytosineHMDB FluorcytosineHMDB Dermatech brand OF flucytosineMeSH Roche brand OF flucytosineMeSH AlcobonMeSH CSP Brand OF flucytosineMeSH ICN pharmaceuticals brand OF flucytosineMeSH Allphar brand OF flucytosineMeSH

Chemical Formlia

C4H4FN3O Average Molecliar Weight

129.0925 Monoisotopic Molecliar Weight

129.03383997 IUPAC Name

6-amino-5-fluoro-1,2-dihydropyrimidin-2-one Traditional Name

flucytosine CAS Registry Number

2022-85-7 SMILES

NC1=C(F)C=NC(=O)N1

InChI Identifier

InChI=1S/C4H4FN3O/c5-2-1-7-4(9)8-3(2)6/h1H,(H3,6,7,8,9)

InChI Key

XRECTZIEBJDKEO-UHFFFAOYSA-N Chemical Taxonomy Description

This compound 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. Kingdom

Organic compounds Super Class

Organoheterocyclic compounds Class

Diazines Sub Class

Pyrimidines and pyrimidine derivatives Direct Parent

Halopyrimidines Alternative Parents

  • Pyrimidones
  • Aminopyrimidines and derivatives
  • Hydropyrimidines
  • Aryl fluorides
  • Heteroaromatic compounds
  • Azacyclic compounds
  • Primary amines
  • Organopnictogen compounds
  • Organooxygen compounds
  • Organofluorides
  • Organic oxides
  • Hydrocarbon derivatives

    • 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

    • Molecliar Framework

    Aromatic heteromonocyclic compounds External Descriptors

  • organofluorine compound (CHEBI:5100 )
  • aminopyrimidine (CHEBI:5100 )
  • pyrimidone (CHEBI:5100 )
  • nucleoside analogue (CHEBI:5100 )
  • pyrimidine antifungal drug (CHEBI:5100 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Antifungal Agents
  • Antifungals
  • Antimetabolites

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Cytoplasm

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point296 °CNot Available Boiling PointNot AvailableNot Available Water Solubility1.92e+00 g/LNot Available LogP-1.1Not Available

    Predicted Properties

    Property Value Source Water Solubility1.92 mg/mLALOGPS 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 Å2ChemAxon Rotatable Bond Count0ChemAxon Refractivity38.22 m3·mol-1ChemAxon Polarizability9.97 Å3ChemAxon Number of Rings1ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-002r-9400000000-acd1b588a4052f6fc2ddView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-002r-9400000000-a4e7dd3c4c886861c0eaView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-000i-9200000000-b3fb9cad9c2b375b08c6View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-000i-9100000000-11fb61e55faa71878d87View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-000i-9000000000-13935b6ab4a3d8adaa08View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , negativesplash10-000i-9000000000-cd981efe159dd44555f4View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , positivesplash10-001i-0900000000-a228aa7f5ecaf516455fView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , positivesplash10-001i-0900000000-ec5b7f7d9f3c75649dc2View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QTOF , positivesplash10-03e9-0900000000-15df2a7b685c4dd4ca17View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-001i-0900000000-7110f8accb80c700a2a5View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-001i-0900000000-89290e0501d587938afbView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-001i-0900000000-7248b6df062077397b61View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-001i-1900000000-df83e87e1bcbc8311be6View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-01q9-3900000000-42649a5ceee8a4619fc3View in MoNA LC-MS/MS

    LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-08gr-9800000000-8cb7a586d34dd7913561View in MoNA Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

    Biological Properties Cellliar Locations

  • Cytoplasm

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01099

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01099

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Predicted Concentrations

    Biofluid Value Original age Original sex Original condition Comments Blood0-8 uMAdlit (>18 years old)BothNormalPredicted based on drug qualities Blood0-4 umol/mmol creatinineAdlit (>18 years old)BothNormalPredicted based on drug qualities

    Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB01099 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    3249 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Flucytosine NuGOwiki Link

    HMDB15231 Metagene Link

    HMDB15231 METLIN ID

    Not Available PubChem Compound

    3366 PDB ID

    Not Available ChEBI ID

    5100

    Product: GSK2141796

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. 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. [PubMed:20843616 ]
    2. 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. [PubMed:19359114 ]
    3. 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. [PubMed:16831406 ]

    Enzymes

    General function:
    Involved in DNA 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:
    184817.425
    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. Shieh FK, Reich NO: AdoMet-dependent methyl-transfer: Glu119 is essential for DNA C5-cytosine methyltransferase M.HhaI. J Mol Biol. 2007 Nov 9;373(5):1157-68. Epub 2007 Aug 19. [PubMed:17897676 ]
    4. 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. [PubMed:8441637 ]

    PMID: 2836439

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