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Record Information
Version2.0
Creation Date2009-06-08 20:21:21 UTC
Update Date2014-12-24 20:22:52 UTC
Accession NumberT3D0836
Identification
Common NameMethoxsalen
ClassSmall Molecule
DescriptionMethoxsalen is only found in individuals that have used or taken this drug. It is a naturally occurring furocoumarin compound found in several species of plants, including Psoralea corylifolia. It is a photoactive substance that forms DNA adducts in the presence of ultraviolet A irradiation. After activation Methoxsalen binds preferentially to the guanine and cytosine moieties of DNA, leading to cross-linking of DNA, thus inhibiting DNA synthesis and function.
Compound Type
  • Aromatic Hydrocarbon
  • Cross-Linking Reagent
  • Drug
  • Ester
  • Ether
  • Food Toxin
  • Furocoumarin
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Photosensitizing Agent
  • Pigmenting Agent
  • Plant Toxin
Chemical Structure
Thumb
Synonyms
Synonym
6-Hydroxy-7-methoxy-5-benzofuranacrylic acid delta-lactone
8-Methoxy-2',3',6,7-furocoumarin
8-Methoxy-4',5':6,7-furocoumarin
8-Methoxy-[furano-3'.2':6.7-coumarin]
8-Methoxyfuranocoumarin
8-Methoxypsoralen
8-MOP
8-MP
9-Methoxy-7H-furo[3,2-g][1]benzopyran-7-one
Ammoidin
Deltasoralen
Meladinine
Meloxine
Methoxalen
Méthoxsalène
O-Methylxanthotoxol
Oxsoralen
Oxsoralen-Ultra
Ultra mop
Uvadex
Xanthotoxin
Xanthotoxine
Xanthoxin
Zanthotoxin
Chemical FormulaC12H8O4
Average Molecular Mass216.190 g/mol
Monoisotopic Mass216.042 g/mol
CAS Registry Number298-81-7
IUPAC Name9-methoxy-7H-furo[3,2-g]chromen-7-one
Traditional Namemethoxsalen
SMILESCOC1=C2OC(=O)C=CC2=CC2=C1OC=C2
InChI IdentifierInChI=1S/C12H8O4/c1-14-12-10-8(4-5-15-10)6-7-2-3-9(13)16-11(7)12/h2-6H,1H3
InChI KeyInChIKey=QXKHYNVANLEOEG-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as 8-methoxypsoralens. These are psoralens containing a methoxy group attached at the C8 position of the psoralen group.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassCoumarins and derivatives
Sub ClassFuranocoumarins
Direct Parent8-methoxypsoralens
Alternative Parents
Substituents
  • 8-methoxypsoralen
  • 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
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point148°C
Boiling PointNot Available
Solubility47.6 mg/L (at 30°C)
LogP1.7
Predicted Properties
PropertyValueSource
Water Solubility0.16 g/LALOGPS
logP2.1ALOGPS
logP1.78ChemAxon
logS-3.1ALOGPS
pKa (Strongest Basic)-2.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area48.67 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity56.85 m³·mol⁻¹ChemAxon
Polarizability20.98 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00ri-6940000000-921a3e8adbbde5f7a0c3JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-003b-4950000000-4e2c001531825f6dddcaJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00ri-6940000000-921a3e8adbbde5f7a0c3JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-003b-4950000000-4e2c001531825f6dddcaJSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-000i-1920000000-98f6cfda190045d0762aJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-014i-1590000000-f70cf2b0756e8c80c17bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-014i-0890000000-f76d6fb28854a5d7b6cdJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0fk9-0920000000-c2bd0b76c5aed757e904JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-014i-0090000000-cecd035cc60695427f78JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0gb9-0290000000-2e17076c991ea61ced1aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0uk9-0970000000-59c3b8004baa44f8d3a5JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-014i-0190000000-cc04ec8c7265ba3a7297JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0udi-0970000000-82c4c7eefd54ad509f69JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-00xs-0900000000-991b5b7dc028219e593bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-0udi-0970000000-dc6cd01d5d2e5eeaae30JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-0udi-0970000000-ee8aa480dca6e72a74fbJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-014i-0890000000-f76d6fb28854a5d7b6cdJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-014i-1590000000-f70cf2b0756e8c80c17bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0fk9-0920000000-c2bd0b76c5aed757e904JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0gi0-1960000000-82bc07f73bc5b2044642JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-014i-0690000000-770dc5d0db7e86d8ba07JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0090000000-4767833559e7bd183ce0JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-0090000000-c471bf567e8a63e00e51JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-01bi-0930000000-72a72a3eb013e045bdb0JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0290000000-c9557f276875a3bf1d2bJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-0390000000-ff927b8db6ef70ef822dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00di-0910000000-d2e511be224be1b3530eJSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-014i-9670000000-3e0fa2e9c81c3bc1d936JSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityMethoxsalen 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. (4).
Metabolism Route of Elimination: In both mice and man, methoxsalen is rapidly metabolized. Approximately 95% of the drug is excreted as a series of metabolites in the urine within 24 hours (Pathak et al. 1977). Half Life: Approximately 2 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Methoxsalen plus UVA radiation is carcinogenic to humans (Group 1). (5)
Uses/SourcesIt is used to increase skin pigmentation with sunlight in the treatment of depigmentation conditions such as vitiligo and may cause skin burns and liver damage. (4). It is als used for the treatment of psoriasis and vitiligo.
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. Furocoumarins 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. (4)
SymptomsHarmful if swallowed. May cause sensitisation by skin contact. (4)
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 IDDB00553
HMDB IDHMDB14693
PubChem Compound ID4114
ChEMBL IDCHEMBL416
ChemSpider ID3971
KEGG IDC01864
UniProt IDNot Available
OMIM ID
ChEBI ID18358
BioCyc ID8-METHOXYFURANOCOUMARIN
CTD IDD008730
Stitch IDXanthotoxin
PDB ID8MO
ACToR IDNot Available
Wikipedia LinkMethoxsalen
References
Synthesis ReferenceNot Available
MSDSLink
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]
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Smith SI, Brodbelt JS: Rapid characterization of cross-links, mono-adducts, and non-covalent binding of psoralens to deoxyoligonucleotides by LC-UV/ESI-MS and IRMPD mass spectrometry. Analyst. 2010 May;135(5):943-52. doi: 10.1039/b924023c. Epub 2010 Feb 12. [20419242 ]
  4. 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 ]
  5. 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 ]
General Function:
Serine hydrolase activity
Specific Function:
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name:
ACHE
Uniprot ID:
P22303
Molecular Weight:
67795.525 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5054 uMNot AvailableBindingDB 50041234
References
  1. Kang SY, Lee KY, Sung SH, Park MJ, Kim YC: Coumarins isolated from Angelica gigas inhibit acetylcholinesterase: structure-activity relationships. J Nat Prod. 2001 May;64(5):683-5. [11374978 ]
General Function:
Serotonin binding
Specific Function:
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine.
Gene Name:
MAOA
Uniprot ID:
P21397
Molecular Weight:
59681.27 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5085.11 uMNot AvailableBindingDB 50041234
References
  1. Santana L, Uriarte E, Gonzalez-Diaz H, Zagotto G, Soto-Otero R, Mendez-Alvarez E: A QSAR model for in silico screening of MAO-A inhibitors. Prediction, synthesis, and biological assay of novel coumarins. J Med Chem. 2006 Feb 9;49(3):1149-56. [16451079 ]
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 ]