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Record Information
Version2.0
Creation Date2009-06-08 16:11:57 UTC
Update Date2014-12-24 20:22:52 UTC
Accession NumberT3D0822
Identification
Common NamePimpinellin
ClassSmall Molecule
DescriptionPimpinellin is a furocoumarin. Furocoumarins, are phototoxic and photocarcinogenic. They intercalate DNA and photochemically induce mutations. Furocoumarins are botanical phytoalexins found to varying extents in a variety of vegetables and fruits, notably citrus fruits. The levels of furocoumarins present in our diets, while normally well below that causing evident acute phototoxicity, do cause pharmacologically relevant drug interactions. Some are particularly active against cytochrome P450s. For example, in humans, bergamottin and dihydroxybergamottin are responsible for the 'grapefruit juice effect', in which these furanocoumarins affect the metabolism of certain drugs.
Compound Type
  • Aromatic Hydrocarbon
  • Ester
  • Ether
  • Food Toxin
  • Furocoumarin
  • Natural Compound
  • Organic Compound
  • Plant Toxin
Chemical Structure
Thumb
Synonyms
Synonym
4-hydroxy-6,7-dimethoxy-5-benzofuranacrylic acid d-lactone
5,6-Dimethoxy-2H-furo[2,3-h]-1-benzopyran-2-one
Chemical FormulaC13H10O5
Average Molecular Mass246.216 g/mol
Monoisotopic Mass246.053 g/mol
CAS Registry Number131-12-4
IUPAC Name5,6-dimethoxy-2H-furo[2,3-h]chromen-2-one
Traditional Namepimpinellin
SMILESCOC1=C(OC)C2=C(OC(=O)C=C2)C2=C1OC=C2
InChI IdentifierInChI=1S/C13H10O5/c1-15-11-7-3-4-9(14)18-10(7)8-5-6-17-12(8)13(11)16-2/h3-6H,1-2H3
InChI KeyInChIKey=BQPRWZCEKZLBHL-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as angular furanocoumarins. These are furanocoumarins, with a structure characterized by a furan ring angularly fused to a coumarin.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassCoumarins and derivatives
Sub ClassFuranocoumarins
Direct ParentAngular furanocoumarins
Alternative Parents
Substituents
  • Angular furanocoumarin
  • Benzopyran
  • 1-benzopyran
  • Benzofuran
  • Anisole
  • Alkyl aryl ether
  • Pyranone
  • Pyran
  • Benzenoid
  • Furan
  • Heteroaromatic compound
  • Lactone
  • Oxacycle
  • Ether
  • Organoheterocyclic compound
  • Organic oxygen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point119°C
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.16 g/LALOGPS
logP2ALOGPS
logP1.63ChemAxon
logS-3.2ALOGPS
pKa (Strongest Basic)-2.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area57.9 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity63.32 m³·mol⁻¹ChemAxon
Polarizability23.88 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0gb9-0190000000-4555870cfdd326d1b0c5JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0090000000-977796ad76d81540e880JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-0090000000-f7a07e2b5e61f4bf192fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0gb9-0590000000-1b90d323aad828c072cbJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0090000000-48f93e3c881c70783662JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-0090000000-8d48f800006b93262426JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-01b9-0960000000-37577186efbdf8f1cd2dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0090000000-14343c13950e873267f5JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-0090000000-14343c13950e873267f5JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0002-0190000000-f32c2dab85f9384c8356JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0090000000-f541a876b9ec3249e209JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-0090000000-3c4660d148cb49d1673aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00kr-0940000000-a01ba3688ec0ee1f1197JSpectraViewer
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityPimpinellin acts as antagonist of proteins with GABA receptor activity (4). The mechanism of action many furocoumarins is based on their ability to form photoadducts with DNA and other cellular components such as RNA, proteins, and several proteins found in the membrane such as phospholipases A2 and C, Ca-dependent and cAMPdependent protein-kinase and epidermal growth factor. Furocoumarins intercalate between base pairs of DNA and after ultraviolet-A irradiation, giving cycloadducts. (4).
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Not listed by IARC. IARC has assessed other furocoumarins, classifying 8-methoxypsoralen as carcinogenic to humans (Group 1), 5-methoxypsoralen as possibly carcinogenic to humans (Group 2A), and certain other furocoumarins as not being classifiable as to their carcinogenicity to humans (Group 3). (5)
Uses/SourcesNot Available
Minimum Risk LevelNot Available
Health EffectsThe furocoumarin 8-methoxypsoralen is carcinogenic to humans, and possibly 5-methoxypsoralen as well (5). There is some evidence from mouse studies that other furocoumarins are carcinogenic when combined with exposure to UVA radiation (1). The SKLM regards the additional risk of skin cancer arising from the consumption of typical quantities of furocoumarin-containing foods, which remain significantly below the range of phototoxic doses, as insignificant. However, the consumption of phototoxic quantities cannot be ruled out for certain foods, particularly celery and parsnips, that may lead to significant increases in furocoumarin concentrations, depending on the storage, processing and production conditions. (6) Furocoumarin photochemotherapy is known to induce a number of side-effects including erythema, edema, hyperpigmentation, and premature aging of skin. All photobiological effects of furocoumarins result from their photochemical reactions. Because many dietary or water soluble furocoumarins are strong inhibitors of cytochrome P450s, they will also cause adverse drug reactions when taken with other drugs. Cause of phototoxicity in patient with vitiligo. (4)
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID4825
ChEMBL IDCHEMBL1491809
ChemSpider ID4659
KEGG IDC09285
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDC039409
Stitch IDPimpinellin
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D0822.pdf
General References
  1. Mullen MP, Pathak MA, West JD, Harrist TJ, Dall'Acqua F: Carcinogenic effects of monofunctional and bifunctional furocoumarins. Natl Cancer Inst Monogr. 1984 Dec;66:205-10. [6531030 ]
  2. Ostertag E, Becker T, Ammon J, Bauer-Aymanns H, Schrenk D: Effects of storage conditions on furocoumarin levels in intact, chopped, or homogenized parsnips. J Agric Food Chem. 2002 Apr 24;50(9):2565-70. [11958623 ]
  3. Santana L, Uriarte E, Roleira F, Milhazes N, Borges F: Furocoumarins in medicinal chemistry. Synthesis, natural occurrence and biological activity. Curr Med Chem. 2004 Dec;11(24):3239-61. [15579011 ]
  4. Herboreal Ltd - Manufacturer of rare phytochemicals (2009). [Link]
  5. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  6. DFG Senate Commission on Food Safety (SKLM): Toxicological Assessment of Furocoumarins in Foodstuffs (2006) [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. Gupta M, Ali R: Fluorescence studies on the interaction of furocoumarins with DNA in the dark. J Biochem. 1984 May;95(5):1253-7. [6746605 ]
  2. Palumbo M, Capasso L, Palu G, Marciani Magno S: DNA-binding of water-soluble furocoumarins: a thermodynamic and conformational approach to understanding different biological effects. Nucleic Acids Res. 1984 Nov 26;12(22):8567-78. [6504703 ]
  3. Herboreal Ltd - Manufacturer of rare phytochemicals (2009). [Link]
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
References
  1. Girennavar B, Jayaprakasha GK, Patil BS: Potent inhibition of human cytochrome P450 3A4, 2D6, and 2C9 isoenzymes by grapefruit juice and its furocoumarins. J Food Sci. 2007 Oct;72(8):C417-21. [17995595 ]
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Girennavar B, Jayaprakasha GK, Patil BS: Potent inhibition of human cytochrome P450 3A4, 2D6, and 2C9 isoenzymes by grapefruit juice and its furocoumarins. J Food Sci. 2007 Oct;72(8):C417-21. [17995595 ]