Tmic
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Record Information
Version2.0
Creation Date2009-06-08 14:27:37 UTC
Update Date2014-12-24 20:22:51 UTC
Accession NumberT3D0815
Identification
Common NameAngelicin
ClassSmall Molecule
DescriptionAngelicin is found in coriander. Angelicin is a constituent of roots and leaves of angelica (Angelica archangelica). Angelicin is found in roots and on surface of parsnips and diseased celery.Angelicin is a furanocoumarin. It can be found in Bituminaria bituminosa. It is present in the list of IARC Group 3 carcinogens (Angelicin plus ultraviolet A radiation). (Wikipedia).
Compound Type
  • Aromatic Hydrocarbon
  • Ester
  • Food Toxin
  • Furocoumarin
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Plant Toxin
Chemical Structure
Thumb
Synonyms
Synonym
2H-Furo[2,3-H]-1-benzopyran-2-one
2H-Furo[2,3-H]chromen-2-one
3-(4-Hydroxy-5-benzofuranyl)-2-propenoic acid gamma-lactone
4-Hydroxy-5-benzofuranacrylic acid gamma-lactone
Angecin
Angelecin
Bakuchicin
Furo[2,3-h]coumarin
Furo[5',4':7,8]coumarin
Isopsoralen
Isopsoralin
Chemical FormulaC11H6O3
Average Molecular Mass186.164 g/mol
Monoisotopic Mass186.032 g/mol
CAS Registry Number523-50-2
IUPAC Name2H-furo[2,3-h]chromen-2-one
Traditional Nameangelicin
SMILESO=C1OC2=C(C=CC3=C2C=CO3)C=C1
InChI IdentifierInChI=1S/C11H6O3/c12-10-4-2-7-1-3-9-8(5-6-13-9)11(7)14-10/h1-6H
InChI KeyInChIKey=XDROKJSWHURZGO-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
  • Pyranone
  • Pyran
  • Benzenoid
  • Furan
  • Heteroaromatic compound
  • Lactone
  • Oxacycle
  • Organoheterocyclic compound
  • Organooxygen compound
  • Organic oxygen 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 Point138 - 139.5°C
Boiling PointNot Available
SolubilityNot Available
LogP2.08
Predicted Properties
PropertyValueSource
Water Solubility0.15 g/LALOGPS
logP2.03ALOGPS
logP1.94ChemAxon
logS-3.1ALOGPS
pKa (Strongest Basic)-2.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area39.44 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity50.39 m³·mol⁻¹ChemAxon
Polarizability17.93 ųChemAxon
Number of Rings3ChemAxon
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, Positivesplash10-052o-1900000000-e433073a06547646bc69View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0900000000-aa1adff2459dc4ba52deView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-0900000000-e3913fd1e50c49b503ccView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00kb-0900000000-1a7322ca712708e85891View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0900000000-0fb3e93d63c26fc514f3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-0900000000-9305ce66dc73cd6363e7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00ko-1900000000-d860e98711eaf835ef5dView in MoNA
MSMass Spectrum (Electron Ionization)splash10-000i-2900000000-b75bda2977a6c5f4a825View in MoNA
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityThe 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. (5)
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Angelicin plus ultraviolet A radiation is not classifiable as to its carcinogenicity to humans (Group 3). (6)
Uses/SourcesAngelicin is used as tranquilliser, sedative, or anticonvulsant. (5)
Minimum Risk LevelNot Available
Health EffectsFurocoumarins can cause photosensitization dermatitis especially if these compounds come into contact with the skin. Some furocoumarins, especially bifunctional furocoumarins, are known to be carcinogenic (1). 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. Limited evidence of carcinogenic effect. (5)
SymptomsHarmful by inhalation, in contact with skin and if swallowed. Irritating to eyes, respiratory system and skin. (5)
TreatmentIf inhaled, remove to fresh air. If not breathing give artificial respiration. If breathing is difficult, give oxygen. If swallowed, wash out mouth with water provided person is conscious. Call physician. In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. (5)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB33930
PubChem Compound ID10658
ChEMBL IDCHEMBL53569
ChemSpider ID10208
KEGG IDC09060
UniProt IDNot Available
OMIM ID
ChEBI ID28928
BioCyc IDNot Available
CTD IDC011659
Stitch IDAngelicin
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkAngelicin
References
Synthesis ReferenceNot Available
MSDSNot Available
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. Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.
  5. Herboreal Ltd - Manufacturer of rare phytochemicals (2009). [Link]
  6. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [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 ]
General Function:
Transcriptional repressor activity, rna polymerase ii transcription regulatory region sequence-specific binding
Specific Function:
NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function, although processing of NFKB1/p105 also appears to occur post-translationally. p50 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105.
Gene Name:
NFKB1
Uniprot ID:
P19838
Molecular Weight:
105355.175 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC502.5 uMNot AvailableBindingDB 50331545
References
  1. Piccagli L, Borgatti M, Nicolis E, Bianchi N, Mancini I, Lampronti I, Vevaldi D, Dall'Acqua F, Cabrini G, Gambari R: Virtual screening against nuclear factor kappaB (NF-kappaB) of a focus library: Identification of bioactive furocoumarin derivatives inhibiting NF-kappaB dependent biological functions involved in cystic fibrosis. Bioorg Med Chem. 2010 Dec 1;18(23):8341-9. doi: 10.1016/j.bmc.2010.09.063. Epub 2010 Oct 1. [20980154 ]