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T3D3735 - Dicoumarol

Record Information
Version 1.0
Creation Date 2010-05-05 18:02:55 UTC
Update Date 2013-04-25 08:48:48 UTC
Accession Number T3D3735
Identification
Common Name Dicoumarol
Description Dicoumarol is a mycotoxin of combined plant and fungal origin. It is a derivative of coumarin, a substance made by plants which is transformed in mouldy feeds by a number of species of fungi into active dicoumarol. Dicoumarol is an anticoagulant that functions as a Vitamin K antagonist. It is used along with heparin for the treatment of deep venous thrombosis, as well as in biochemical experiments as an inhibitor of reductases. (W846)
Compound Type
  • Organic Compound
  • Mycotoxin
  • Anticoagulant
  • Vitamin K Antagonist
Chemical Structure
Thumb
MOL SDF SMILES InChI
Synonyms
  1. 2-hydroxy-3-[(2-hydroxy-4-oxochromen-3-yl)methyl]chromen-4-one
  2. 2H-1-Benzopyran-2-one), 3,3'-methylenebis(4-hydroxy-
  3. 2H-1-Benzopyran-2-one, 3,3'-methylenebis(4-hydroxy)-
  4. 2H-1-Benzopyran-2-one, 3,3'-methylenebis(4-hydroxy-
  5. 2H-1-Benzopyran-2-one, 3,3'-methylenebis[4-hydroxy-
  6. 2H-1-Benzopyran-2-one, 3,3'-methylenebis[4-hydroxy- (9CI)
  7. 2H-1-Benzopyran-2-one], 3,3'-methylenebis[4-hydroxy-
  8. 3,3 -Methylene-bis[4-hydroxycoumarin]
  9. 3,3'-methanediylbis(4-hydroxy-2H-chromen-2-one)
  10. 3,3'-Methyleen-bis(4-hydroxy-cumarine)
  11. 3,3'-Methyleen-bis(4-hydroxy-cumarine) [Dutch]
  12. 3,3'-Methylen-bis(4-hydroxy-cumarin)
  13. 3,3'-Methylen-bis(4-hydroxy-cumarin) [German]
  14. 3,3'-Methylene-bis(4-hydroxycoumarin)
  15. 3,3'-Methylene-bis(4-hydroxycoumarine)
  16. 3,3'-Methylene-bis(4-hydroxycoumarine) [French]
  17. 3,3'-Methylenebis(4-hydroxy-1,2-benzopyrone)
  18. 3,3'-Methylenebis(4-hydroxy-2H-1-benzopyran-2-one)
  19. 3,3'-methylenebis(4-hydroxy-2H-chromen-2-one)
  20. 3,3'-methylenebis(4-hydroxy-coumarin
  21. 3,3'-Methylenebis(4-hydroxycoumarin)
  22. 3,3'-Methylenebis[4-hydroxy-1,2-benzopyrone]
  23. 3,3'-Methylenebis[4-hydroxy-2H-1-benzopyran-2-one]
  24. 3,3'-Methylenebis[4-hydroxycoumarin]
  25. 3,3'-Metilen-bis(4-idrossi-cumarina)
  26. 3,3'-Metilen-bis(4-idrossi-cumarina) [Italian]
  27. 3,3′-Methylenebis(4-hydroxycoumarin)
  28. 4,4'-Dihydroxy-3,3'-methylene bis coumarin
  29. 4-hydroxy-3-((4-hydroxy-2-oxo-2H-chromen-3-yl)methyl)-2H-chromen-2-one
  30. 4-hydroxy-3-(4-hydroxy-2-oxo-2H-3-chromenylmethyl)-2H-2-chromenone
  31. 4-hydroxy-3-[(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl]-2H-chromen-2-one
  32. Acadyl
  33. Acavyl
  34. Anathrombase
  35. Antitrombosin
  36. Apekumarol
  37. Baracoumin
  38. BHC
  39. Bis(4-hydroxycoumarin-3-yl)methane
  40. Bis-3,3'-(4-hydroxycoumarinyl)methane
  41. Bis-3,3'-(4-oxycoumarinyl)ethylacetate
  42. bis-hydroxycoumarin
  43. Bishydroxycoumarin
  44. Bishydroxycoumarin4-hydroxy-3-(4-hydroxy-2-oxo-2H-3-chromenylmethyl)-2H-2-chromenone
  45. Coumarin, 3,3'-methylenebis(4-hydroxy-
  46. Coumarin, 3,3'-methylenebis[4-hydroxy-
  47. Coumarin, 3,3'-methylenebis[4-hydroxy- (8CI)
  48. Cuma
  49. Cumid
  50. Di-(4-hydroxy-3-coumarinyl)methane
  51. Di-4-hydroxy-3,3'-methylenedicoumarin
  52. Dicoumal
  53. dicoumarin
  54. dicoumarol
  55. Dicoumarol (INN)
  56. Dicoumarolum
  57. Dicoumarolum [INN-Latin]
  58. Dicoumerol
  59. Dicuman
  60. Dicumaol R
  61. Dicumarine
  62. Dicumarinum
  63. dicumarol
  64. Dicumarol (TN)
  65. Dicumarol (USAN)
  66. Dicumarol [INN-Spanish]
  67. Dicumarol [USAN]
  68. Dicumarolo
  69. Dicumarolo [DCIT]
  70. Dicumarolum
  71. Dicumol
  72. DTC
  73. Dufalone
  74. Dwukumarol
  75. Dwukumarol [Polish]
  76. Kumoran
  77. melitoxin
  78. Temparin
  79. Trombosan
Chemical Formula C19H12O6
Average Molecular Weight 336.295
Monoisotopic Molecular Weight 336.063388116
Chemical IUPAC Name
dicumarol
CAS Registry Number 66-76-2
SMILES
OC1=C(CC2=C(O)OC3=CC=CC=C3C2=O)C(=O)C2=CC=CC=C2O1
InChI Identifier
InChI=1S/C19H12O6/c20-16-10-5-1-3-7-14(10)24-18(22)12(16)9-13-17(21)11-6-2-4-8-15(11)25-19(13)23/h1-8,22-23H,9H2
InChI Key InChIKey=KSKRYQVHJQRUNC-UHFFFAOYSA-N
Chemical Taxonomy
Kingdom Organic Compounds
Super Class Phenylpropanoids and Polyketides
Class Coumarins and Derivatives
Sub Class Not Available
Direct Parent Coumarins and Derivatives
Alternative Parents
  • Chromones
  • Pyranones and Derivatives
  • Benzene and Substituted Derivatives
  • Aldehydes
Molecular Framework Aromatic Heteropolycyclic Compounds
Substituents
  • benzene
  • aldehyde
  • pyran
  • pyranone
External Descriptors Not Available
DrugBank ID Not Available
PubChem Compound ID 653 Link_out
KEGG ID Not Available
UniProt ID Not Available
OMIM ID Not Available
ChEBI ID Not Available
BioCyc ID Not Available
CTD ID Not Available
Stitch ID Not Available
PDB ID Not Available
ACToR ID Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Dicoumarol Link_out
Physical Properties
Appearance Not Available
Melting Point Not Available
Solubility Not Available
Predicted LogP -0.19872933289927552
Toxicity Profile
Route of Exposure Oral, dermal, inhalation, and parenteral (contaminated drugs). (W967)
Mechanism of Action Dicoumarol is an anticoagulant that competitively inhibits vitamin K, preventing the formation of prothrombin. It does this by inhibiting the enzyme NAD(P)H:quinone oxidoreductase-1, which is required for the reduction of vitamin K to its hydroquinone. Reduced vitamin K is a cofactor needed in the conversion of prothrombin precursor protein to active prothrombin, an essential protein for blood clotting. In addition, inhibition of NAD(P)H:quinone oxidoreductase-1 induces the generation of superoxide anion radicals that inhibit cell growth. Dicoumarol can also potently and reversible inhibit gap junctional intercellular communication, though the precise mechanism is unknown. (W846, W847, W848, W849, W850)
Metabolism Not Available
Toxicity Values Not Available
Lethal Dose LD50: 233 mg/kg (Oral, Mouse) (S405)
Carcinogenicity (IARC Classification) Not Available
Uses/Sources Dicoumarol is a mycotoxin of combined plant and fungal origin. It is a derivative of coumarin, a substance made by plants which is transformed in mouldy feeds by a number of species of fungi into active dicoumarol. Dicoumarol is an anticoagulant that is used along with heparin for the treatment of deep venous thrombosis, as well as in biochemical experiments as an inhibitor of reductases. (W846)
Minimum Risk Level Not Available
Health Effects Dicoumarol is an anticoagulant. (W846)
Symptoms Dicoumarol can cause bleeding complications. (W846)
Treatment Administration of Vitamin K is the antidote for dicoumarol toxicity. (W846)
References
General References
  • W846 — Wikipedia, Dicoumarol. Last Updated 29 April 2010. [Link]
  • W847 — Cullen JJ, Hinkhouse MM, Grady M, Gaut AW, Liu J, Zhang YP, Weydert CJ, Domann FE, Oberley LW. Dicumarol inhibition of NADPH:quinone oxidoreductase induces growth inhibition of pancreatic cancer via a superoxide-mediated mechanism. Cancer Res. 2003 Sep 1;63(17):5513-20. [14500388 Link_out]
  • W848 — Abdelmohsen K, Stuhlmann D, Daubrawa F, Klotz LO. Dicumarol is a potent reversible inhibitor of gap junctional intercellular communication. Arch Biochem Biophys. 2005 Feb 15;434(2):241-7. [15639223 Link_out]
  • W849 — Preusch PC, Smalley DM. Vitamin K1 2,3-epoxide and quinone reduction: mechanism and inhibition. Free Radic Res Commun. 1990;8(4-6):401-15. [2113031 Link_out]
  • W850 — Nelsestuen GL, Suttie JW. The mode of action of vitamin K. Isolation of a peptide containing the vitamin K-dependent portion of prothrombin. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3366-70. [4519629 Link_out]
  • S405 — DrugBank: a knowledgebase for drugs, drug actions and drug targets. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. [18048412 Link_out]
  • W967 — Peraica M, Domijan AM. Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 Link_out]

Targets

1. NAD(P)H dehydrogenase [quinone] 1

The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinons involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.

Dicoumarol is an anticoagulant that competitively inhibits vitamin K, preventing the formation of prothrombin. It does this by inhibiting the enzyme NAD(P)H:quinone oxidoreductase-1, which is required for the reduction of vitamin K to its hydroquinone. Reduced vitamin K is a cofactor needed in the conversion of prothrombin precursor protein to active prothrombin, an essential protein for blood clotting. In addition, inhibition of NAD(P)H:quinone oxidoreductase-1 induces the generation of superoxide anion radicals that inhibit cell growth. Dicoumarol can also potently and reversible inhibit gap junctional intercellular communication, though the precise mechanism is unknown. (W846, W847, W848, W849, W850)
UniProt ID: P15559 Link_out
Gene: NQO1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
References:
  • W846 — Wikipedia, Dicoumarol. Last Updated 29 April 2010. [Link]
  • W847 — Cullen JJ, Hinkhouse MM, Grady M, Gaut AW, Liu J, Zhang YP, Weydert CJ, Domann FE, Oberley LW. Dicumarol inhibition of NADPH:quinone oxidoreductase induces growth inhibition of pancreatic cancer via a superoxide-mediated mechanism. Cancer Res. 2003 Sep 1;63(17):5513-20. [14500388 Link_out]
  • W849 — Preusch PC, Smalley DM. Vitamin K1 2,3-epoxide and quinone reduction: mechanism and inhibition. Free Radic Res Commun. 1990;8(4-6):401-15. [2113031 Link_out]
  • W850 — Nelsestuen GL, Suttie JW. The mode of action of vitamin K. Isolation of a peptide containing the vitamin K-dependent portion of prothrombin. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3366-70. [4519629 Link_out]