Methoxsalen

Methoxsalen

File:Methoxsalen.svg
Systematic (IUPAC) name
9-methoxy-7H-furo[3,2-g]chromen-7-one
Pharmacokinetic data
Biological half-life	~2 hours
Identifiers
CAS Number	298-81-7
ATC code	D05AD02 (WHO) D05BA02
PubChem	CID 4114
DrugBank	APRD00157
Chemical data
Formula	C12H8O4
Molar mass	216.19 g/mol[[]]
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Methoxsalen also called xanthotoxin and metoxaleno (marketed under the trade name Oxsoralen , Dltasoralen , 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 Umbelliferae. Methoxsalen modifies the way skin cells receive the UVA radiation, allegedly clearing up the disease. The dosage comes in 10mg tablets, which are taken in the amount of 30mg 75 minutes before a PUVA light treatment. The substance is also present in bergamot oil which is used in many perfumes and aromatherapy oils.

Biosynthesis of Xanthotoxin

Introduction Xanthotoxin, also known as Methoxsalen, is a drug that can be used to treat various skin disorder. The molecular structure of the molecule belong to a group of molecule known as furanocoumarin which are a class of organic natural molecules which consist of coumarin coupled with a furan. The biosynthetic path way of Xanthotoxin is a mixture of the Shikimate pathway and the Mevalonate pathway.

Synthesis of Umbelliferone The biosynthetic pathway of Xanthotoxin first begins with the formation of Umbelliferone, a phenylpropanoid, that can be made from the Shikimate Pathway. The starting material is L-Phe which get lysated into cinnamic acid follow by hydroxylation of the cinnamic acid by cinnamate 4-hydroxylase to yield 4-coumaric acid. The 4-coumaric acid then further get 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 acetic acid group. Finally an intramolecular attack from the hydroxyl group of C2' to the acetic acid group closes the ring and form a lactone which yield umbelliferone.

Synthesis of Xanthotoxin. The biosynthetic route then switches to the Mavelonate Pathway in which DMAPP is first activated to form a carbo-cation via the cleavage of the diphosphates. Once activated, the enzyme umbelliferone 6-prenyltransferase then 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 then occur using psoralen synthase to yield psoralen. A third hydroxylation by the enzyme psoralen 8-monooxygenase yield xanthotoxol which is followed by a methylation via the enzyme xanthotoxol O-methyltransferase and SAM to yield xanthotoxin.

References.

Dewick, P. M. Medicinal Natural Products: A Biosynthetic Approach. 3rd Edition ed.; John Wiley & Sons Ltd: 2009; 161.

Dewick, P. M. Medicinal Natural Products: A Biosynthetic Approach. 3rd Edition ed.; John Wiley & Sons Ltd: 2009; 164-165.

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. When Eau de Cologne was made, it became a popular perfume. It contained bergamot oil as one of its components. Ladies wearing the perfume on places where the skin was radiated by the sun, noticed that their skin turned brownish at those spots. This is due to the phototoxic effects of methoxsalen present in the bergamot oil. The methoxsalen was removed, and most modern formulations of perfumes containing bergamot are de-methoxsalenised.

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.

References

de:Xanthotoxin