Bergamottin (T3D0834)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (3)XML
Targets (3)
Record Information
Version2.0
Creation Date2009-06-08 18:13:20 UTC
Update Date2014-12-24 20:22:52 UTC
Accession NumberT3D0834
Identification
Common NameBergamottin
ClassSmall Molecule
DescriptionBergamottin is found in citrus. Bergamottin is a constituent of bergamot oil. Also from lemon oil and oils of other Citrus species and carrot (Daucus carota) Bergamottin is a natural furanocoumarin found principally in grapefruit juice. It is also found in the oil of bergamot, from which it was first isolated and from which its name is derived. To a lesser extent, bergamottin is also present in the essential oils of other citrus fruits. Along with the chemically related compound 6 ,7 -dihydroxybergamottin, it is believed to be responsible for the grapefruit juice effect in which the consumption of the juice affects the metabolism of a variety of pharmaceutical drugs. Bergamottin has been shown to exhibit anti-tumor function (1).
Compound Type
  • Aromatic Hydrocarbon
  • Ester
  • Ether
  • Food Toxin
  • Furocoumarin
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Plant Toxin
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
4-[(3,7-Dimethyl-2,6-octadienyl)oxy]-7H-furo[3,2-g][1]benzopyran-7-one, 9CI
5-Geranoxypsoralen
5-Geranyloxypsoralen
Bergamotin
Bergamotine
Bergaptin
Bergaptol geranyl ether
Chemical FormulaC21H22O4
Average Molecular Mass338.397 g/mol
Monoisotopic Mass338.152 g/mol
CAS Registry Number7380-40-7
IUPAC Name4-{[(2E)-3,7-dimethylocta-2,6-dien-1-yl]oxy}-7H-furo[3,2-g]chromen-7-one
Traditional Namebergamottin
SMILES[H]\C(COC1=C2C=COC2=CC2=C1C=CC(=O)O2)=C(\C)CCC=C(C)C
InChI IdentifierInChI=1S/C21H22O4/c1-14(2)5-4-6-15(3)9-11-24-21-16-7-8-20(22)25-19(16)13-18-17(21)10-12-23-18/h5,7-10,12-13H,4,6,11H2,1-3H3/b15-9+
InChI KeyInChIKey=DBMJZOMNXBSRED-OQLLNIDSSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as terpene lactones. These are prenol lipids containing a lactone ring.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassPrenol lipids
Sub ClassTerpene lactones
Direct ParentTerpene lactones
Alternative Parents
Substituents
  • Terpene lactone
  • Linear furanocoumarin
  • Furanocoumarin
  • Psoralen
  • Coumarin
  • Benzopyran
  • 1-benzopyran
  • Monoterpenoid
  • Aromatic monoterpenoid
  • Benzofuran
  • Alkyl aryl ether
  • Pyranone
  • Benzenoid
  • Pyran
  • Furan
  • Heteroaromatic compound
  • Lactone
  • Oxacycle
  • Organoheterocyclic compound
  • Ether
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organooxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
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 Point59 - 61°C
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.01 g/LALOGPS
logP5.3ALOGPS
logP4.81ChemAxon
logS-4.5ALOGPS
pKa (Strongest Basic)-2.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area48.67 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity99.77 m³·mol⁻¹ChemAxon
Polarizability37.74 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-1449000000-f1cb80e88623323efd782016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00kr-7974000000-8dc8885c8ce63b6b8f052016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0uxr-9420000000-d4a732b567f78ee66d362016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0059000000-6c5381fc4c44ea7b815b2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-0392000000-aef5d498f581369a14952016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-0910000000-f3479b11ac7337bdd5d42016-08-03View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityBergamottin is a potent chemopreventive agent against aflatoxin B1-inducible cyotoxicity in H4IIE cells with a bifunctional effects on glutathione S-transferase and CYP1A. Potent inhibitor and inactivator of cytochrome P450 1A1-mediated monooxygenase in both murine hepatic microsomes and in a reconstituted system using purified human P450 1A1 (6). 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. (6)
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). (7)
Uses/SourcesNot Available
Minimum Risk LevelNot Available
Health EffectsThe furocoumarin 8-methoxypsoralen is carcinogenic to humans, and possibly 5-methoxypsoralen as well (7). There is some evidence from mouse studies that other furocoumarins are carcinogenic when combined with exposure to UVA radiation (2). 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. (8) 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.
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB33782
PubChem Compound ID7251175
ChEMBL IDNot Available
ChemSpider ID5584831
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDC068337
Stitch IDBergamottin
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkBergamottin
References
Synthesis ReferenceNot Available
MSDST3D0834.pdf
General References
  1. Hwang YP, Yun HJ, Choi JH, Kang KW, Jeong HG: Suppression of phorbol-12-myristate-13-acetate-induced tumor cell invasion by bergamottin via the inhibition of protein kinase Cdelta/p38 mitogen-activated protein kinase and JNK/nuclear factor-kappaB-dependent matrix metalloproteinase-9 expression. Mol Nutr Food Res. 2010 Jul;54(7):977-90. doi: 10.1002/mnfr.200900283. [19943262 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.
  6. Herboreal Ltd - Manufacturer of rare phytochemicals (2009). [Link]
  7. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  8. DFG Senate Commission on Food Safety (SKLM): Toxicological Assessment of Furocoumarins in Foodstuffs (2006) [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

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]
Target Details
2. Cytochrome P450 2C9
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 ]
Target Details
3. Cytochrome P450 3A4
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 ]