Psoralen: Difference between revisions
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| Formula = C<sub>11</sub>H<sub>6</sub>O<sub>3</sub> |
| Formula = C<sub>11</sub>H<sub>6</sub>O<sub>3</sub> |
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| MolarMass = 186.16 g/mol |
| MolarMass = 186.16 g/mol |
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| MeltingPt = |
| MeltingPt = 158–161 °C |
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| Density = }} |
| Density = }} |
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}} |
}} |
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An important use of psoralen is in [[PUVA]] treatment for skin problems such as [[psoriasis]] and (to a lesser extent) eczema and [[vitiligo]]. This takes advantage of the high [[Ultraviolet|UV]] absorbance of psoralen. The psoralen is applied first to sensitise the skin, then UVA light is applied to clean up the skin problem. Psoralen has also been recommended for treating [[alopecia]]. Psoralens are also used in photopheresis where they are mixed with the extracted leukocytes before UV radiation is applied. |
An important use of psoralen is in [[PUVA]] treatment for skin problems such as [[psoriasis]] and (to a lesser extent) eczema and [[vitiligo]]. This takes advantage of the high [[Ultraviolet|UV]] absorbance of psoralen. The psoralen is applied first to sensitise the skin, then UVA light is applied to clean up the skin problem. Psoralen has also been recommended for treating [[alopecia]]. Psoralens are also used in photopheresis where they are mixed with the extracted leukocytes before UV radiation is applied. |
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Psoralen is a [[mutagen]] and is used for this purpose in molecular biology research. Psoralen intercalates into the DNA and, on exposure to ultraviolet (UVA) radiation, can form covalent interstrand cross-links (ICL) with thymines preferentially at 5'-TpA sites in the genome, inducing [[apoptosis]]. Psoralen plus UVA (PUVA) therapy has shown considerable clinical efficacy.<ref> |
Psoralen is a [[mutagen]] and is used for this purpose in molecular biology research. Psoralen intercalates into the DNA and, on exposure to ultraviolet (UVA) radiation, can form covalent interstrand cross-links (ICL) with thymines preferentially at 5'-TpA sites in the genome, inducing [[apoptosis]]. Psoralen plus UVA (PUVA) therapy has shown considerable clinical efficacy.<ref>{{cite journal |author=Wu Q, Christensen LA, Legerski RJ, Vasquez KM |title=Mismatch repair participates in error-free processing of DNA interstrand crosslinks in human cells |journal=EMBO Rep. |volume=6 |issue=6 |pages=551–7 |year=2005 |month=June |pmid=15891767 |pmc=1369090 |doi=10.1038/sj.embor.740041810.1038/sj.embor.7400418}}</ref> Unfortunately, a side effect of PUVA treatment is a higher risk of skin cancer.<ref>{{cite journal |author=Momtaz K, Fitzpatrick TB |title=The benefits and risks of long-term PUVA photochemotherapy |journal=Dermatol Clin |volume=16 |issue=2 |pages=227–34 |year=1998 |month=April |pmid=9589196 }}</ref> |
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Despite the [[photocarcinogen]]ic properties of psoralen,<ref name=Ashwood1980> {{cite journal |author=M. J. Ashwood-Smith; G. A. Poulton; M. Barker; M. Mildenberger E |title=5-Methoxypsoralen, an ingredient in several suntan preparations, has lethal, mutagenic and clastogenic properties |url= |
Despite the [[photocarcinogen]]ic properties of psoralen,<ref name=Ashwood1980> {{cite journal |author=M. J. Ashwood-Smith; G. A. Poulton; M. Barker; M. Mildenberger E |title=5-Methoxypsoralen, an ingredient in several suntan preparations, has lethal, mutagenic and clastogenic properties |url=http://www.nature.com/nature/journal/v285/n5764/abs/285407a0.html |journal=Nature |volume=285 |issue=5 |pages=407–9 |year=1980 |pmid=6991953 |doi=10.1038/285407a0 }}</ref> |
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<ref name=Zajdela1981> |
<ref name=Zajdela1981>{{cite journal |author=Zajdela F, Bisagni E. |title=5-Methoxypsoralen, the melanogenic additive in sun-tan preparations, is tumorigenic in mice exposed to 365 nm UV radiation. |url=http://carcin.oxfordjournals.org/cgi/content/abstract/2/2/121 |journal=Carcinogenesis |volume=1981 |issue=2 |pages=121–7 |year=1981 |doi=10.1093/carcin/2.2.121}}</ref> It had been used as a [[tanning activator]] in sunscreens until 1996.<ref name=Autier1997> {{cite journal |author=Autier P., Dore J.-F., Cesarini J.-P. |title=Should subjects who used psoralen suntan activators be screened for melanoma?|url=http://www.springerlink.com/content/t6222620211w50w9/ |journal=Annals of Oncology |volume=8 |issue=5 |pages=435–7 |year=1997 |pmid=9233521 |doi=10.1023/A:1008205513771}}</ref> |
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Psoralens are used in tanning accelerators, but users should keep in mind that psoralen increases your skin’s sensitivity to light. |
Psoralens are used in tanning accelerators, but users should keep in mind that psoralen increases your skin’s sensitivity to light. |
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Some patients have even had severe skin loss after sunbathing with psoralen containing tanning activators. |
Some patients have even had severe skin loss after sunbathing with psoralen containing tanning activators.<ref>{{cite journal |author=Nettelblad H, Vahlqvist C, Krysander L, Sjöberg F |title=Psoralens used for cosmetic sun tanning: an unusual cause of extensive burn injury |journal=Burns |volume=22 |issue=8 |pages=633–5 |year=1996 |month=December |pmid=8982544 |url=http://linkinghub.elsevier.com/retrieve/pii/S0305417996000289}}</ref> |
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Patients with lighter skin colour suffer four times as much from the melanoma-generating properties of psoralens than those with darker skin<ref name=Autier1997/> |
Patients with lighter skin colour suffer four times as much from the melanoma-generating properties of psoralens than those with darker skin<ref name=Autier1997/> |
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==Biosynthesis== |
==Biosynthesis== |
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Psoralen originates from [[coumarins]] of the [[shikimate]] pathway; its biosynthesis is shown in the figure below. The aromatic ring in 6 is activated at positions ortho to the hydroxyl group, and is alkylated by 5, an alkylating agent. The dimethylallyl group in 7 then undergoes cyclization with the phenol group to give 8. This transformation is catalysed by a cytochome P-450-dependent monooxygenase17 (psoralen 5-monooxygenase), and cofactors ([[NADPH]]) and molecular oxygen.<ref>Dewick, P. |
Psoralen originates from [[coumarins]] of the [[shikimate]] pathway; its biosynthesis is shown in the figure below. The aromatic ring in 6 is activated at positions ortho to the hydroxyl group, and is alkylated by 5, an alkylating agent. The dimethylallyl group in 7 then undergoes cyclization with the phenol group to give 8. This transformation is catalysed by a cytochome P-450-dependent monooxygenase17 (psoralen 5-monooxygenase), and cofactors ([[NADPH]]) and molecular oxygen.<ref name=Dewick09>{{cite book |author=Dewick, P.M. |title=Medicinal Natural Products: A Biosynthetic Approach |publisher=Wiley |year=2009 |pages=164–5 |edition=3rd }}</ref> |
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Another biosynthesis pathway of psoralen is shown below in the figure. A second P-450-dependent monooxygenase enzyme ([[psoralen synthase]]) then cleaves off 10 (in the form of 11) from 8 to give 1. This pathway does not involve any hydroxylated intermediate, and cleavage is postulated to be initiated by a [[radical reaction]]. |
Another biosynthesis pathway of psoralen is shown below in the figure. A second P-450-dependent monooxygenase enzyme ([[psoralen synthase]]) then cleaves off 10 (in the form of 11) from 8 to give 1. This pathway does not involve any hydroxylated intermediate, and cleavage is postulated to be initiated by a [[radical reaction]].<ref name=Dewick09/> |
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<!-- Deleted image removed: [[Image:Psoralen Biosynthesis 2.jpg|350px|center|Biosynthesis of psoralen from a second P-450 dependent monooxygenase]] --> |
<!-- Deleted image removed: [[Image:Psoralen Biosynthesis 2.jpg|350px|center|Biosynthesis of psoralen from a second P-450 dependent monooxygenase]] --> |
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==Further reading== |
==Further reading== |
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# F. |
#{{cite book |author=Dean, F.M. |title=Naturally Occurring Oxygen Ring Compounds |publisher=Butterworths |location=London |year=1963 }} |
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# |
#{{cite book |title=The Merck Index |publisher=Merck |location=Rahway NJ |year=1960 |edition=7th }} |
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{{coumarin}} |
{{coumarin}} |
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Revision as of 12:03, 16 December 2010
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| Names | |
|---|---|
| IUPAC names
7H-furo[3,2-g]chromen-7-one or
7H-furo[3,2-g]benzopyran-7-one | |
| Identifiers | |
3D model (JSmol)
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| ChemSpider | |
| ECHA InfoCard | 100.000.581 |
CompTox Dashboard (EPA)
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| |
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| Properties | |
| C11H6O3 | |
| Molar mass | 186.16 g/mol |
| Melting point | 158–161 °C |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
| |
Psoralen (also called psoralene) is the parent compound in a family of natural products known as furocoumarins. It is structurally related to coumarin by the addition of a fused furan ring, and may be considered as a derivative of umbelliferone. Psoralen occurs naturally in the seeds of Psoralea corylifolia, as well as in the common Fig, celery, parsley and West Indian satinwood. It is widely used in PUVA (=Psoralen +UVA) treatment for psoriasis, eczema, vitiligo, and cutaneous T-cell lymphoma. Although safe to mammals, it should be used with care since many furocoumarins are extremely toxic to fish, and some are indeed used in streams in Indonesia to catch fish.
Uses
An important use of psoralen is in PUVA treatment for skin problems such as psoriasis and (to a lesser extent) eczema and vitiligo. This takes advantage of the high UV absorbance of psoralen. The psoralen is applied first to sensitise the skin, then UVA light is applied to clean up the skin problem. Psoralen has also been recommended for treating alopecia. Psoralens are also used in photopheresis where they are mixed with the extracted leukocytes before UV radiation is applied.
Psoralen is a mutagen and is used for this purpose in molecular biology research. Psoralen intercalates into the DNA and, on exposure to ultraviolet (UVA) radiation, can form covalent interstrand cross-links (ICL) with thymines preferentially at 5'-TpA sites in the genome, inducing apoptosis. Psoralen plus UVA (PUVA) therapy has shown considerable clinical efficacy.[1] Unfortunately, a side effect of PUVA treatment is a higher risk of skin cancer.[2]
Despite the photocarcinogenic properties of psoralen,[3] [4] It had been used as a tanning activator in sunscreens until 1996.[5] Psoralens are used in tanning accelerators, but users should keep in mind that psoralen increases your skin’s sensitivity to light. Some patients have even had severe skin loss after sunbathing with psoralen containing tanning activators.[6] Patients with lighter skin colour suffer four times as much from the melanoma-generating properties of psoralens than those with darker skin[5]
Chemistry
One isomer of psoralen is angelicin, and most furocoumarins can be regarded as derivatives of psoralen or angelicin. Some important psoralen derivatives are Imperatorin, xanthotoxin, bergapten and nodekenetin.
Another important feature of this class of compounds is its ability in generating singlet oxygen.
Structure
The structure of psoralen was originally deduced using its degradation reactions. It exhibits the normal reactions of the lactone of coumarin, such as ring opening by alkali to give a coumarinic acid or coumaric acid derivative. Potassium permanganate causes oxidation of the furan ring, while other methods of oxidation produce furan-2,3-carboxylic acid.
Synthesis
Psoralen synthesis is challenging, due the fact that umbelliferone undergoes substitution at the 8-position rather than at the desired 6 position. Benzofuran reacts preferentially in the furan ring rather than in the benzene ring. However the 7-hydroxy derivative of 2,3-dihydrobenzofuran (also called coumaran) does undergo substitution at the desired 6-position allowing the following synthesis of the coumarin system via a Gattermann-Koch reaction followed by a Perkin condensation using acetic anhydride. The synthesis is then completed by dehydrogenation of the five-membered ring to produce the furan ring.
Biosynthesis
Psoralen originates from coumarins of the shikimate pathway; its biosynthesis is shown in the figure below. The aromatic ring in 6 is activated at positions ortho to the hydroxyl group, and is alkylated by 5, an alkylating agent. The dimethylallyl group in 7 then undergoes cyclization with the phenol group to give 8. This transformation is catalysed by a cytochome P-450-dependent monooxygenase17 (psoralen 5-monooxygenase), and cofactors (NADPH) and molecular oxygen.[7]
Another biosynthesis pathway of psoralen is shown below in the figure. A second P-450-dependent monooxygenase enzyme (psoralen synthase) then cleaves off 10 (in the form of 11) from 8 to give 1. This pathway does not involve any hydroxylated intermediate, and cleavage is postulated to be initiated by a radical reaction.[7]
External links
- Institute for Traditional Medicine vitiligo article
- ibiblio page on Psoralea corylifolia
- USDA ARS info on uses & plants
References
- ^ Wu Q, Christensen LA, Legerski RJ, Vasquez KM (2005). "Mismatch repair participates in error-free processing of DNA interstrand crosslinks in human cells". EMBO Rep. 6 (6): 551–7. doi:10.1038/sj.embor.740041810.1038/sj.embor.7400418. PMC 1369090. PMID 15891767.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Momtaz K, Fitzpatrick TB (1998). "The benefits and risks of long-term PUVA photochemotherapy". Dermatol Clin. 16 (2): 227–34. PMID 9589196.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ M. J. Ashwood-Smith; G. A. Poulton; M. Barker; M. Mildenberger E (1980). "5-Methoxypsoralen, an ingredient in several suntan preparations, has lethal, mutagenic and clastogenic properties". Nature. 285 (5): 407–9. doi:10.1038/285407a0. PMID 6991953.
{{cite journal}}: no-break space character in|author=at position 6 (help)CS1 maint: multiple names: authors list (link) - ^ Zajdela F, Bisagni E. (1981). "5-Methoxypsoralen, the melanogenic additive in sun-tan preparations, is tumorigenic in mice exposed to 365 nm UV radiation". Carcinogenesis. 1981 (2): 121–7. doi:10.1093/carcin/2.2.121.
- ^ a b Autier P., Dore J.-F., Cesarini J.-P. (1997). "Should subjects who used psoralen suntan activators be screened for melanoma?". Annals of Oncology. 8 (5): 435–7. doi:10.1023/A:1008205513771. PMID 9233521.
{{cite journal}}: no-break space character in|author=at position 7 (help)CS1 maint: multiple names: authors list (link) - ^ Nettelblad H, Vahlqvist C, Krysander L, Sjöberg F (1996). "Psoralens used for cosmetic sun tanning: an unusual cause of extensive burn injury". Burns. 22 (8): 633–5. PMID 8982544.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b Dewick, P.M. (2009). Medicinal Natural Products: A Biosynthetic Approach (3rd ed.). Wiley. pp. 164–5.
Further reading
- Dean, F.M. (1963). Naturally Occurring Oxygen Ring Compounds. London: Butterworths.
- The Merck Index (7th ed.). Rahway NJ: Merck. 1960.