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Record Information
Version2.0
Creation Date2009-06-08 20:46:01 UTC
Update Date2014-12-24 20:22:52 UTC
Accession NumberT3D0838
Identification
Common NameImperatorin
ClassSmall Molecule
DescriptionImperatorin is found in anise. Imperatorin is present in Aegle marmelos (bael fruit) and seeds of Pastinaca sativa (parsnip).Imperatorin is a furocoumarin and a phytochemical that has been isolated from Urena lobata L. (Malvaceae). It is biosynthesized from umbelliferone, a coumarin derivative. Imperatorin has been shown to exhibit anti-hypertrophic and anti-convulsant functions (1, 2). Imperatorin belongs to the family of Furanocoumarins. These are polycyclic aromatic compounds containing a furan ring fused to a coumarin moeity.
Compound Type
  • Aromatic Hydrocarbon
  • Ester
  • Ether
  • Food Toxin
  • Furocoumarin
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Plant Toxin
Chemical Structure
Thumb
Synonyms
Synonym
5-Hydroxy-8-(1,1-dimethylallyl)psoralen
8-Isoamylenoxypsoralen
9-(3-Methyl-2-butenyloxy)-7-oxofuro[3,2-g]chromene
9-(3-Methylbut-2-enyloxy)-7H-furo(3,2-g)chromen-7-one
9-(3-Methylbut-2-enyloxy)furo[3,2-g]chromen-7-one
9-[(3-Methyl-2-butenyl)oxy]-7H-furo[3,2-g][1]benzopyran-7-one, 9CI
9-[(3-Methylbut-2-en-1-yl)oxy]-7H-furo[3,2-g]chromen-7-one
Ammidin
Marmelide
Marmelosin
Pentasalen, BAN
Chemical FormulaC16H14O4
Average Molecular Mass270.280 g/mol
Monoisotopic Mass270.089 g/mol
CAS Registry Number482-44-0
IUPAC Name9-[(3-methylbut-2-en-1-yl)oxy]-7H-furo[3,2-g]chromen-7-one
Traditional Nameimperatorin
SMILESCC(C)=CCOC1=C2OC(=O)C=CC2=CC2=C1OC=C2
InChI IdentifierInChI=1S/C16H14O4/c1-10(2)5-7-19-16-14-12(6-8-18-14)9-11-3-4-13(17)20-15(11)16/h3-6,8-9H,7H2,1-2H3
InChI KeyInChIKey=OLOOJGVNMBJLLR-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as psoralens. These are organic compounds containing a psoralen moiety, which consists of a furan fused to a chromenone to for 7H-furo[3,2-g]chromen-7-one.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassCoumarins and derivatives
Sub ClassFuranocoumarins
Direct ParentPsoralens
Alternative Parents
Substituents
  • Psoralen
  • Benzopyran
  • 1-benzopyran
  • Benzofuran
  • Alkyl aryl ether
  • Pyranone
  • Benzenoid
  • Pyran
  • Heteroaromatic compound
  • Furan
  • Lactone
  • Ether
  • Oxacycle
  • Organoheterocyclic compound
  • 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 Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point102°C
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.034 g/LALOGPS
logP3.62ALOGPS
logP3.15ChemAxon
logS-3.9ALOGPS
pKa (Strongest Basic)-2.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area48.67 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity75.97 m³·mol⁻¹ChemAxon
Polarizability28.33 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, Positivesplash10-0q4l-5490000000-8addd2b7e7d5a89c1657JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-1090000000-205792cde142f77aa94fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-9080000000-7795cfce5b3fcd729d41JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0uxu-9540000000-7130c7ebffd168204435JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0090000000-6f0805a46d8f54b963d2JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-0290000000-cdea20e125d3564dc0caJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-1920000000-a1c90224178c9971284dJSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-0udi-3290000000-ccce724ec532a9b1c7aeJSpectraViewer | MoNA
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityImperatorin is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen. 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. (7).
MetabolismParaoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of OP exposure.
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). (8)
Uses/SourcesNot Available
Minimum Risk LevelNot Available
Health EffectsAcute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides. The furocoumarin 8-methoxypsoralen is carcinogenic to humans, and possibly 5-methoxypsoralen as well (8). There is some evidence from mouse studies that other furocoumarins are carcinogenic when combined with exposure to UVA radiation (3). 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. (9) 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. (7)
SymptomsSymptoms of low dose exposure include excessive salivation and eye-watering. Acute dose symptoms include severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Hypertension, hypoglycemia, anxiety, headache, tremor and ataxia may also result.
TreatmentIf the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB34376
PubChem Compound ID10212
ChEMBL IDCHEMBL453805
ChemSpider ID9797
KEGG IDC09269
UniProt IDNot Available
OMIM ID
ChEBI ID5885
BioCyc IDPHYTOALEXIN-CMPD
CTD IDC031534
Stitch IDImperatorin
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkImperatorin
References
Synthesis ReferenceNot Available
MSDST3D0838.pdf
General References
  1. Zhang Y, Cao Y, Zhan Y, Duan H, He L: Furanocoumarins-imperatorin inhibits myocardial hypertrophy both in vitro and in vivo. Fitoterapia. 2010 Dec;81(8):1188-95. doi: 10.1016/j.fitote.2010.07.023. Epub 2010 Aug 4. [20691250 ]
  2. Luszczki JJ, Andres-Mach M, Glensk M, Skalicka-Wozniak K: Anticonvulsant effects of four linear furanocoumarins, bergapten, imperatorin, oxypeucedanin, and xanthotoxin, in the mouse maximal electroshock-induced seizure model: a comparative study. Pharmacol Rep. 2010 Nov-Dec;62(6):1231-6. [21273683 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.
  7. Herboreal Ltd - Manufacturer of rare phytochemicals (2009). [Link]
  8. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  9. 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 ]
General Function:
Protein tyrosine/serine/threonine phosphatase activity
Specific Function:
Shows activity both for tyrosine-protein phosphate and serine-protein phosphate, but displays a strong preference toward phosphotyrosines. Specifically dephosphorylates and inactivates ERK1 and ERK2.
Gene Name:
DUSP3
Uniprot ID:
P51452
Molecular Weight:
20478.1 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>100 uMNot AvailableBindingDB 50308719
References
  1. Liu D, Kong G, Chen QC, Wang G, Li J, Xu Y, lin T, Tian Y, Zhang X, Yao X, Feng G, Lu Z, Chen H: Fatty acids as natural specific inhibitors of the proto-oncogenic protein Shp2. Bioorg Med Chem Lett. 2011 Nov 15;21(22):6833-7. doi: 10.1016/j.bmcl.2011.09.023. Epub 2011 Sep 13. [21962577 ]
General Function:
Protein tyrosine phosphatase activity
Specific Function:
Protein phosphatase that acts preferentially on tyrosine-phosphorylated MAPK1. Plays a role in the regulation of T and B-lymphocyte development and signal transduction.
Gene Name:
PTPN7
Uniprot ID:
P35236
Molecular Weight:
40528.965 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>100 uMNot AvailableBindingDB 50308719
References
  1. Liu D, Kong G, Chen QC, Wang G, Li J, Xu Y, lin T, Tian Y, Zhang X, Yao X, Feng G, Lu Z, Chen H: Fatty acids as natural specific inhibitors of the proto-oncogenic protein Shp2. Bioorg Med Chem Lett. 2011 Nov 15;21(22):6833-7. doi: 10.1016/j.bmcl.2011.09.023. Epub 2011 Sep 13. [21962577 ]