Methoxsalen

Methoxsalen
Methoxsalen
Systematic (IUPAC) name
9-methoxy-7H-furo[3,2-g]chromen-7-one
Clinical data
AHFS/Drugs.com Consumer Drug Information
Pregnancy cat.  ?
Legal status  ?
Pharmacokinetic data
Half-life ~2 hours
Identifiers
CAS number 298-81-7 YesY
ATC code D05AD02 D05BA02
PubChem CID 4114
DrugBank APRD00157
ChemSpider 3971 YesY
UNII U4VJ29L7BQ YesY
KEGG D00139 YesY
ChEBI CHEBI:18358 N
ChEMBL CHEMBL416 YesY
Chemical data
Formula C12H8O4 
Mol. mass 216.19 g/mol
SMILES eMolecules & PubChem
 N(what is this?)  (verify)

Methoxsalen (also called xanthotoxin, marketed under the trade names Oxsoralen, Deltasoralen, Meladinine) is a drug used to treat psoriasis, eczema, vitiligo, and some cutaneous Lymphomas in conjunction with exposing the skin to sunlight. Methoxsalen is extracted from Ammi majus, a plant of the family Apiaceae. Methoxsalen modifies the way skin cells receive the UVA radiation, allegedly clearing up the disease. The dosage comes in 10 mg tablets, which are taken in the amount of 30 mg 75 minutes before a PUVA (psoralen + UVA) light treatment. The substance is also present in other Apiaceae as well as Rutaceae, for example bergamot oil which is used in many perfumes and aromatherapy oils.

Chemically, methoxsalen belongs to a class of organic natural molecules known as furanocoumarins. They consist of coumarin annulated with furan.

Contents

Biosynthesis

The biosynthetic pathway is a combination of the shikimate pathway, which produces umbelliferone, and the mevalonate pathway.

Synthesis of umbelliferone

Umbelliferone is a phenylpropanoid and as such is synthesized from L-phenylalanine, which in turn is produced via the shikimate pathway. Phenylalanine is lysated into cinnamic acid, followed by hydroxylation by cinnamate 4-hydroxylase to yield 4-coumaric acid. The 4-coumaric acid is again hydroxylated by cinnamate/coumarate 2-hydroxylase to yield 2,4-dihydroxy-cinnamic acid followed by a bond rotation of the unsaturated bond adjacent to the carboxylic acid group. Finally an intramolecular attack from the hydroxyl group of C2' to the carboxylic acid group closes the ring and forms the lactone umbelliferone.

Synthesis of methoxsalen

The biosynthetic route then continues with the activation of dimethylallyl pyrophosphate (DMAPP), produced via the mevalonate pathway, to form a carbo-cation via the cleavage of the diphosphates. Once activated, the enzyme umbelliferone 6-prenyltransferase catalyzes a C-alkylation between DMAPP and umbelliferone at the activated position ortho to the phenol, yielding demethylsuberosin. This is then followed by a hydroxylation catalyzed by the enzyme marmesin synthase to yield marmesin. Another hydroxylation is catalyzed by psoralen synthase to yield psoralen. A third hydroxylation by the enzyme psoralen 8-monooxygenase yields xanthotoxol which is followed by a methylation via the enzyme xanthotoxol O-methyltransferase and S-adenosyl methionine to yield methoxsalen.[1]

Risks and side effects

Patients with high blood pressure or a history of liver problems are at risk for inflammation and irreparable damage to both liver and skin. The eyes must be protected from UVA radiation. Side effects include nausea, headaches, dizziness, and in rare cases insomnia.

Cultural aspects

Author John Howard Griffin used the chemical to darken his skin in order to investigate racial segregation in the south. He wrote the non-fiction book Black Like Me about his experiences.[2]

Some cologne/perfume contains bergamot oil as one of the ingredients (for the scent). People wearing the concoction on places where the skin receives UV radiation was radiated by the sun noticed that their skin turned brownish at those spots (due to the phototoxic effects of methoxsalen present in the bergamot oil[3]). Most modern formulations of perfumes containing bergamot are de-methoxsalenised.

References

  1. ^ Dewick, P. M. (2009). Medicinal Natural Products: A Biosynthetic Approach (3rd ed.). John Wiley & Sons. pp. 161, 164–165. 
  2. ^ Dead Like Me on snopes.com
  3. ^ "Bergamot". oilsandplants.com. http://www.oilsandplants.com/bergamot.htm. Retrieved 2010-12-29. 

Wikimedia Foundation. 2010.

Игры ⚽ Нужна курсовая?

Look at other dictionaries:

  • Methoxsalen — Strukturformel Allgemeines Freiname Methoxsalen Andere Namen 9 Methoxy 7H fu …   Deutsch Wikipedia

  • methoxsalen topical solution — [USP] a preparation containing 9.2 to 10.8 mg of methoxsalen per mL; used in conjunction with exposure to ultraviolet light to facilitate repigmentation in idiopathic vitiligo …   Medical dictionary

  • methoxsalen — /me thok seuh leuhn/, n. Pharm. a potent compound, C12H8O4, derived from the seeds of the plant Ammi majus: used in combination with certain ultraviolet radiation for the treatment of severe psoriasis. [METHOX(Y) + (P)S(OR)ALEN] * * * …   Universalium

  • methoxsalen — A methoxypsoralen derivative that increases melanin production in the skin when exposed to ultraviolet light; used orally and topically in the treatment of idiopathic vitiligo, and also as a suntan accelerator and sun protectant. * * *… …   Medical dictionary

  • Methoxsalen — Meth|ox|sa|len [Kurzw. für 8 Methoxypsoralen]: svw. ↑ Xanthotoxin …   Universal-Lexikon

  • methoxsalen — A drug used together with UV light to treat psoriasis, vitiligo, and skin nodules of cutaneous T cell lymphoma. It is also being studied in the treatment of graft versus host disease. It belongs to the family of drugs called psoralens and… …   English dictionary of cancer terms

  • methoxsalen — /me thok seuh leuhn/, n. Pharm. a potent compound, C12H8O4, derived from the seeds of the plant Ammi majus: used in combination with certain ultraviolet radiation for the treatment of severe psoriasis. [METHOX(Y) + (P)S(OR)ALEN] …   Useful english dictionary

  • Coal tar — is a brown or black liquid of extremely high viscosity, which smells of naphthalene and aromatic hydrocarbons. Coal tar is among the by products when coal is carbonized to make coke or gasified to make coal gas. Coal tars are complex and variable …   Wikipedia

  • ATC code D05 — A section of the Anatomical Therapeutic Chemical Classification System.D DermatologicalsD05A Antipsoriatics for topical useD05AA TarsD05AC Antracen derivatives:D05AC01 Dithranol:D05AC51 Dithranol, combinationsD05AD Psoralens for topical… …   Wikipedia

  • Acitretin — Systematic (IUPAC) name (2E,4E,6E,8E) 9 (4 methoxy 2,3,6 trimethylphenyl) 3,7 dimethylnona 2,4,6,8 tetraenoic acid Clinical data Trade n …   Wikipedia

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”