Psoralen

Last updated
Psoralen
Psoralen.svg
Names
Preferred IUPAC name
7H-Furo[3,2-g][1]benzopyran-7-one
Identifiers
3D model (JSmol)
152784
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.000.581 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 200-639-7
KEGG
PubChem CID
UNII
  • InChI=1S/C11H6O3/c12-11-2-1-7-5-8-3-4-13-9(8)6-10(7)14-11/h1-6H Yes check.svgY
    Key: ZCCUUQDIBDJBTK-UHFFFAOYSA-N Yes check.svgY
  • O=C1/C=C\c2cc3ccoc3cc2O1
Properties
C11H6O3
Molar mass 186.16 g/mol
Melting point 158 to 161 °C (316 to 322 °F; 431 to 434 K)
Hazards
GHS labelling:
GHS-pictogram-exclam.svg
Warning
H302, H315, H319, H335
P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

Psoralen (also called psoralene) is the parent compound in a family of naturally occurring organic compounds known as the linear furanocoumarins. 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, West Indian satinwood, and in all citrus fruits. It is widely used in PUVA (psoralen + UVA) treatment for psoriasis, eczema, vitiligo, and cutaneous T-cell lymphoma; these applications are typically through the use of medications such as Methoxsalen. Many furanocoumarins are extremely toxic to fish, and some are deposited in streams in Indonesia to catch fish. [1]

Contents

Uses

Psoralen is a mutagen, and is used for this purpose in molecular biology research. Psoralen intercalates into DNA and on exposure to ultraviolet (UVA) radiation can form monoadducts and covalent interstrand cross-links (ICL) with thymines, preferentially at 5'-TpA sites in the genome, inducing apoptosis. Psoralen plus UVA (PUVA) therapy can be used to treat hyperproliferative skin disorders like psoriasis and certain kinds of skin cancer. [2] Unfortunately, PUVA treatment itself leads to a higher risk of skin cancer. [3]

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 address the condition. Psoralens are also used in photopheresis, where they are mixed with the extracted leukocytes before UV radiation is applied.

Despite the photocarcinogenic properties of psoralen, [4] [5] it was used as a tanning activator in sunscreens until 1996. [6] Psoralens are used in tanning accelerators, because psoralen increases the skin's sensitivity to light. Some patients have had severe skin loss after sunbathing with psoralen-containing tanning activators. [7] Patients with lighter skin colour suffer four times as much from the melanoma-generating properties of psoralens than those with darker skin. [6] Psoralens short term side effects include nausea, vomiting, erythrema, pruritus, xerosis, skin pain due to phototoxic damage of dermal nerve and may cause cutaneous and genital skin malignancies. [8]

An additional use for optimized psoralens is for the inactivation of pathogens in blood products. The synthetic amino-psoralen, amotosalen HCl, has been developed for the inactivation of infectious pathogens (bacteria, viruses, protozoa) in platelet and plasma blood components prepared for transfusion support of patients. Prior to clinical use, amotosalen-treated platelets have been tested and found to be non-carcinogenic when using the established p53 knockout mouse model. [9] The technology is currently in routine use in certain European blood centers and has been recently approved in the US. [10] [11] [12] [13]

Chemistry

Psoralen intercalates into the DNA double helix where it is ideally positioned to form one or more adducts with adjacent pyrimidine bases, preferentially thymine, upon excitation by an ultraviolet photon.

Several physicochemical methods have been employed to derive binding constants for psoralen-DNA interactions. Classically, two chambers of psoralen and buffered DNA solution are partitioned by a semi-permeable membrane; the affinity of the psoralen for DNA is directly related to the concentration of the psoralen in the DNA chamber after equilibrium. Water solubility is important for two reasons: pharmacokinetics relating to drug solubility in blood and necessitating the use of organic solvents (e.g. DMSO). Psoralens can also be activated by irradiation with long wavelength UV light. While UVA range light is the clinical standard, research that UVB is more efficient at forming photoadducts suggests that its use may lead to higher efficacy and lower treatment times. [14]

The photochemically reactive sites in psoralens are the alkene-like carbon-carbon double bonds in the furan ring (the five-member ring) and the pyrone ring (the six-member ring). When appropriately intercalated adjacent to a pyrimidine base, a four-center photocycloaddition reaction can lead to the formation of either of two cyclobutyl-type monoadducts. Ordinarily, furan-side monoadducts form in a higher proportion. The furan monoadduct can absorb a second UVA photon leading to a second four-center photocycloaddition at the pyrone end of the molecule and hence the formation of a diadduct or cross-link. Pyrone monoadducts do not absorb in the UVA range and hence cannot form cross-links with further UVA irradiation. [15]

Another important feature of this class of compounds is their ability to generate singlet oxygen, although this process is in direct competition with adduct formation and may be an alternate pathway for the dissipation of excited state energy.

Research on psoralen has historically focused on interactions with DNA and RNA (in particular, ICL formation). Psoralen, however, has also been shown to block signaling of the ErbB2 receptor which is overexpressed in certain aggressive types of breast cancer. [16] A synthetic derivative of bergapten, 5-(4-phenoxybutoxy)psoralen, shows promise as an immunosuppressant by inhibiting a specific potassium channel. Its structure prevents intercalation into DNA, and it only very weakly produces singlet oxygen, majorly reducing unwanted toxicity and mutagenicity in vivo. This has implications for the treatment of various autoimmune diseases (e.g. multiple sclerosis, type-1 diabetes, and rheumatoid arthritis). [17] While cell-surface modification and ion channel blocking are two newly discovered mechanisms of action, much research remains to be done.

Structure

Most furanocoumarins can be regarded as derivatives of either psoralen or angelicin. Psoralen and its derivatives are often referred to as the linear furanocoumarins, so called since they exhibit a linear chemical structure. Important linear furanocoumarins include xanthotoxin (also called methoxsalen), bergapten, imperatorin, and nodakenetin.

Structures of angelicin, xanthotoxin, bergapten and nodekenetin Psoralen derivatives.png
Structures of angelicin, xanthotoxin, bergapten and nodekenetin

The structure of psoralen was originally deduced by identifying the products of 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 is difficult to synthesize because 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.

Synthesis of psoralen from 6-hydroxycoumaran Psoralen synthesis.png
Synthesis of psoralen from 6-hydroxycoumaran

Biosynthesis

Psoralen originates from coumarins in 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 cytochrome P-450-dependent monooxygenase17 (psoralen 5-monooxygenase), and cofactors (NADPH) and molecular oxygen. [18]

A biosynthetic pathway in which psoralen is formed is shown in the figure below. 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. [18]

Synthesis of psoralen from 6-hydroxycoumaran Bergamottin biosynthesis.svg
Synthesis of psoralen from 6-hydroxycoumaran

Plant sources

Ficus carica (fig) is probably the most abundant source of psoralens. They are also found in small quantities in Ammi visnaga (bisnaga), Pastinaca sativa (parsnip), Petroselinum crispum (parsley), Levisticum officinale (lovage), Foeniculum vulgare (fruit, i.e., fennel seeds), Daucus carota (carrot), Psoralea corylifolia (babchi), Apium graveolens (celery), bergamot oil (bergapten, bergamottin). [19]

Repair of psoralen DNA adducts

PUVA treatment produces both DNA interstrand crosslinks (ICLs) and monoadducts. The ICLs introduced by psoralen are highly genotoxic to actively replicating cells. The covalent linkage impedes replication fork progression. Thus unlinking the ICL is required before replication can resume. The initial steps in repair ordinarily involve incisions in one parental strand on both sides of the crosslink. [20] Subsequently, repair of the lesion can occur by an accurate or an inaccurate process.

The accurate process for repairing crosslinks is homologous recombinational repair (HRR). This involves replacing the damaged information using the intact information from another homologous chromosome in the same cell. Escherichia coli cells deficient in HRR are highly sensitive to PUVA compared to wild-type cells. [21] HRR appears to be efficient. In E. coli, even though one or two unrepaired crosslinks are sufficient to inactivate a cell, a wild-type cell can repair and therefore recover from 53 to 71 psoralen crosslinks. [21] In the yeast Saccharomyces cerevisiae HRR is a major pathway for accurately removing psoralen-crosslinks. [22] In wild-type yeast, the recombination events associated with crosslink removal by HRR are predominantly non-crossover gene conversion events. Psoralen crosslinks in virus DNA also appear to be removed by a recombinational repair process as occurs in SV40 virus infected cells, [23] and in herpes simplex virus infected cells. [24]

One inaccurate process for repairing psoralen crosslinks appears to employ a DNA polymerase to fill in the gap formed in the strand with the two incisions. This process is inaccurate because the complementary un-incised strand still retains a portion of the crosslink and thus cannot serve as an adequate template for accurate repair synthesis. Inaccurate repair synthesis can cause mutation. Psoralen monoadducts in the template DNA strand may also cause inaccurate replication bypass (translesion synthesis) that can lead to mutation. In phage T4, the increase in mutation observed after PUVA treatment was found to reflect translesion synthesis by wild-type DNA polymerase, likely due to imperfect proof reading capability.

Analysis of nucleic acids structures

Psoralens can reversibly crosslink nucleic acids double helices, and therefore have been used extensively for the analysis of interactions and structures for both DNA and RNA. [25] [26]

Related Research Articles

<span class="mw-page-title-main">Benzofuran</span> Heterocyclic compound consisting of fused benzene and furan rings

Benzofuran is the heterocyclic compound consisting of fused benzene and furan rings. This colourless liquid is a component of coal tar. Benzofuran is the structural nucleus of many related compounds with more complex structures. For example, psoralen is a benzofuran derivative that occurs in several plants.

PUVA is an ultraviolet light therapy treatment for skin diseases: vitiligo, eczema, psoriasis, graft-versus-host disease, mycosis fungoides, large plaque parapsoriasis, and cutaneous T-cell lymphoma, using the sensitizing effects of the drug psoralen. The psoralen is applied or taken orally to sensitize the skin, then the skin is exposed to UVA.

<span class="mw-page-title-main">Methoxsalen</span> Chemical compound

Methoxsalen sold under the brand name Oxsoralen among others, is a medication used to treat psoriasis, eczema, vitiligo, and some cutaneous lymphomas in conjunction with exposing the skin to ultraviolet (UVA) light from lamps or sunlight. Methoxsalen modifies the way skin cells receive the UVA radiation, allegedly clearing up the disease. Levels of individual patient PUVA exposure were originally determined using the Fitzpatrick scale. The scale was developed after patients demonstrated symptoms of phototoxicity after oral ingestion of methoxsalen followed by PUVA therapy. Chemically, methoxsalen belongs to a class of organic natural molecules known as furanocoumarins. They consist of coumarin annulated with furan. It can also be injected and used topically.

<span class="mw-page-title-main">Nitrogen mustard</span> Family of chemical compounds

Nitrogen mustards (NMs) are cytotoxic organic compounds with the bis(2-chloroethyl)amino ((ClC2H4)2NR) functional group. Although originally produced as chemical warfare agents, they were the first chemotherapeutic agents for treatment of cancer. Nitrogen mustards are nonspecific DNA alkylating agents.

<span class="mw-page-title-main">Dithranol</span> Chemical compound

Dithranol (INN) or anthralin is a hydroxyanthrone, anthracene derivative, and is used in medications applied to the skin of people with psoriasis. It is available as creams, ointment or pastes in 0.1 to 2% strengths. The terms dithranol and anthralin are sometimes used synonymously.

Topoisomerase inhibitors are chemical compounds that block the action of topoisomerases, which are broken into two broad subtypes: type I topoisomerases (TopI) and type II topoisomerases (TopII). Topoisomerase plays important roles in cellular reproduction and DNA organization, as they mediate the cleavage of single and double stranded DNA to relax supercoils, untangle catenanes, and condense chromosomes in eukaryotic cells. Topoisomerase inhibitors influence these essential cellular processes. Some topoisomerase inhibitors prevent topoisomerases from performing DNA strand breaks while others, deemed topoisomerase poisons, associate with topoisomerase-DNA complexes and prevent the re-ligation step of the topoisomerase mechanism. These topoisomerase-DNA-inhibitor complexes are cytotoxic agents, as the un-repaired single- and double stranded DNA breaks they cause can lead to apoptosis and cell death. Because of this ability to induce apoptosis, topoisomerase inhibitors have gained interest as therapeutics against infectious and cancerous cells.

<span class="mw-page-title-main">Crosslinking of DNA</span> Phenomenon in genetics

In genetics, crosslinking of DNA occurs when various exogenous or endogenous agents react with two nucleotides of DNA, forming a covalent linkage between them. This crosslink can occur within the same strand (intrastrand) or between opposite strands of double-stranded DNA (interstrand). These adducts interfere with cellular metabolism, such as DNA replication and transcription, triggering cell death. These crosslinks can, however, be repaired through excision or recombination pathways.

<span class="mw-page-title-main">Furanocoumarin</span> Class of organic chemical compounds

The furanocoumarins, or furocoumarins, are a class of organic chemical compounds produced by a variety of plants. Most of the plant species found to contain furanocoumarins belong to a handful of plant families. The families Apiaceae and Rutaceae include the largest numbers of plant species that contain furanocoumarins. The families Moraceae and Fabaceae include a few widely distributed plant species that contain furanocoumarins.

<span class="mw-page-title-main">Bergamottin</span> Chemical compound

Bergamottin (5-geranoxypsoralen) is a natural furanocoumarin found in the pulp of pomelos and grapefruits. It is also found in the peel and pulp of the bergamot orange, from which it was first isolated and from which its name is derived.

<span class="mw-page-title-main">Trioxsalen</span> Chemical compound

Trioxsalen (trimethylpsoralen (TMP), trioxysalen (INN) or Trisoralen) is a furanocoumarin and a psoralen derivative. It is obtained from several plants, mainly Psoralea corylifolia. Like other psoralens it causes photosensitization of the skin. It is administered either topically or orally in conjunction with UV-A (the least damaging form of ultraviolet light) for phototherapy treatment of vitiligo and hand eczema. After photoactivation it creates interstrand cross-links in DNA, which can cause programmed cell death unless repaired by cellular mechanisms. In research it can be conjugated to dyes for confocal microscopy and used to visualize sites of DNA damage. The compound is also being explored for development of antisense oligonucleotides that can be cross-linked specifically to a mutant mRNA sequence without affecting normal transcripts differing at even a single base pair.

<span class="mw-page-title-main">ERCC4</span> Protein-coding gene in the species Homo sapiens

ERCC4 is a protein designated as DNA repair endonuclease XPF that in humans is encoded by the ERCC4 gene. Together with ERCC1, ERCC4 forms the ERCC1-XPF enzyme complex that participates in DNA repair and DNA recombination.

<span class="mw-page-title-main">FANCL</span> Protein-coding gene in the species Homo sapiens

E3 ubiquitin-protein ligase FANCL is an enzyme that in humans is encoded by the FANCL gene.

Tanning activators are chemicals that increase the effect of UV-radiation on the human skin.

<span class="mw-page-title-main">Phytophotodermatitis</span> Medical condition

Phytophotodermatitis, also known as berloque dermatitis, margarita photodermatitis, lime disease or lime phytodermatitis is a cutaneous phototoxic inflammatory reaction resulting from contact with a light-sensitizing botanical agent followed by exposure to ultraviolet A (UV-A) light. Symptoms include erythema, edema, blisters, and delayed hyperpigmentation. Heat and moisture tend to exacerbate the reaction.

<span class="mw-page-title-main">Bergapten</span> Chemical compound

Bergapten (5-methoxypsoralen) is a naturally-occurring organic chemical compound produced by numerous plant species, especially from the carrot family Apiaceae and the citrus family Rutaceae. For example, bergapten has been extracted from 24 species of the genus Heracleum in the family Apiaceae. In the family Rutaceae, various Citrus species contain significant amounts of bergapten, especially the bergamot orange, the micrantha, and certain varieties of lime and bitter orange.

<span class="mw-page-title-main">Angelicin</span> Chemical compound

Angelicin is the parent compound in a family of naturally occurring organic compounds known as the angular furanocoumarins. Structurally, it can be considered as benzapyra-2-one fused with a furan moiety in the 7,8-position. Angelicin is commonly found in certain Apiaceae and Fabaceae plant species such as Bituminaria bituminosa. It has a skin permeability coefficient (LogKp) of -2.46. The maximum absorption is observed at 300 nm. The 1HNMR spectrum is available; the infrared and mass spectra of angelicin can be found in this database. The sublimation of angelicin occurs at 120 °C and the pressure of 0.13 Pa. Angelicin is a coumarin.

Platinum-based antineoplastic drugs are chemotherapeutic agents used to treat cancer. Their active moieties are coordination complexes of platinum. These drugs are used to treat almost half of people receiving chemotherapy for cancer. In this form of chemotherapy, commonly used drugs include cisplatin, oxaliplatin, and carboplatin, but several have been proposed or are under development. Addition of platinum-based chemotherapy drugs to chemoradiation in women with early cervical cancer seems to improve survival and reduce risk of recurrence.

<span class="mw-page-title-main">Marmesin</span> Chemical compound

Marmesin (nodakenetin) is a chemical compound precursor in psoralen and linear furanocoumarins biosynthesis.

<span class="mw-page-title-main">FAN1</span> Protein-coding gene in the species Homo sapiens

FANCD2/FANCI-associated nuclease 1 (KIAA1018) is an enzyme that in humans is encoded by the FAN1 gene. It is a structure dependent endonuclease. It is thought to play an important role in the Fanconi Anemia (FA) pathway.

<span class="mw-page-title-main">SLX4IP</span> Protein-coding gene in the species Homo sapiens

SLX4 interacting protein is a protein that in humans is encoded by the SLX4IP gene.

References

  1. ↑ Dean, F. M. (1963). Naturally occurring oxygen ring compounds. London: Butterworths.
  2. ↑ Wu Q, Christensen LA, Legerski RJ, Vasquez KM (June 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.7400418. PMC   1369090 . PMID   15891767.
  3. ↑ Momtaz K, Fitzpatrick TB (April 1998). "The benefits and risks of long-term PUVA photochemotherapy". Dermatol Clin. 16 (2): 227–34. doi:10.1016/S0733-8635(05)70005-X. PMID   9589196.
  4. ↑ 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. Bibcode:1980Natur.285..407A. doi:10.1038/285407a0. PMID   6991953. S2CID   4345680.
  5. ↑ Zajdela F, Bisagni E (1981). "5-Methoxypsoralen, the melanogenic additive in suntan preparations, is tumorigenic in mice exposed to 365 nm UV radiation". Carcinogenesis. 2 (2): 121–7. doi:10.1093/carcin/2.2.121. PMID   7273295.
  6. 1 2 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.
  7. ↑ Nettelblad H, Vahlqvist C, Krysander L, Sjöberg F (December 1996). "Psoralens used for cosmetic sun tanning: an unusual cause of extensive burn injury". Burns. 22 (8): 633–5. doi:10.1016/S0305-4179(96)00028-9. PMID   8982544.
  8. ↑ Shenoi, Shrutakirthi D.; Prabhu, Smitha; Indian Association of Dermatologists, Venereologists and Leprologists (November 2014). "Photochemotherapy (PUVA) in psoriasis and vitiligo". Indian Journal of Dermatology, Venereology and Leprology. 80 (6): 497–504. doi: 10.4103/0378-6323.144143 . ISSN   0973-3922. PMID   25382505.
  9. ↑ Ciaravino V, McCullough T, Dayan AD: Pharmacokinetic and toxicology assessment of INTERCEPT (S-59 and UVA treated)platelets. Human Exp Toxicol 2001;20:533–550
  10. ↑ Osselaer; et al. (2009). "Universal adoption of pathogen inactivation of platelet components: impact on platelet and red blood cell component use". Transfusion. 49 (7): 1412–1422. doi:10.1111/j.1537-2995.2009.02151.x. PMID   19389022. S2CID   25477437.
  11. ↑ Cazenave; et al. (2010). "An active hemovigilance program characterizing the safety profile of 7,483 transfusions with plasma components prepared with amotosalen and UVA photochemical treatment". Transfusion. 50 (6): 1210–1219. doi: 10.1111/j.1537-2995.2009.02579.x . PMID   20113450. S2CID   32119458.
  12. ↑ "FDA approves first pathogen reduction system to treat plasma". www.fda.gov. Archived from the original on 2014-12-25.
  13. ↑ "FDA approves pathogen reduction system to treat platelets". www.fda.gov. Archived from the original on 2014-12-25.
  14. ↑ Alexandru D. Buhimschi; Francis P. Gasparro (September 2013). "UVA and UVB-Induced 8-Methoxypsoralen Photoadducts and a Novel Method for their Detection by Surface-Enhanced Laser Desorption Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF MS)". Journal of Photochemistry and Photobiology. 90 (1): 241–246. doi:10.1111/php.12171. PMID   24102188. S2CID   206270126.
  15. ↑ Gasparro, Francis P., ed. (1988). Psoralen DNA photobiology. 1. Boca Raton, Fl: CRC Pr. ISBN   978-0-8493-4379-7.
  16. ↑ Wenle Xia; David Gooden; Leihua Liu; Sumin Zhao; Erik J. Soderblom; Eric J. Toone; Wayne F. Beyer Jr; Harold Walder; Neil L. Spector (February 14, 2014). Cheng, Jin (ed.). "Photo-Activated Psoralen Binds the ErbB2 Catalytic Kinase Domain, Blocking ErbB2 Signaling and Triggering Tumor Cell Apoptosis". PLOS ONE. 9 (2): e88983. Bibcode:2014PLoSO...988983X. doi: 10.1371/journal.pone.0088983 . PMC   3925176 . PMID   24551203.
  17. ↑ Alexander Schmitz; Ananthakrishnan Sankaranarayanan; Philippe Azam; Kristina Schmidt-Lassen; Daniel Homerick; Wolfram Hänsel; Heike Wulff (November 2005). "Design of PAP-1, a selective small molecule Kv1.3 blocker, for the suppression of effector memory T cells in autoimmune diseases". Molecular Pharmacology. 68 (5): 1254–1270. doi:10.1124/mol.105.015669. PMID   16099841. S2CID   6931552.
  18. 1 2 Dewick, P.M. (2009). Medicinal Natural Products: A Biosynthetic Approach (3rd ed.). Wiley. pp.  164–5. ISBN   978-0-471-49641-0.
  19. ↑ "Dr. Duke's Phytochemical and Ethnobotanical Databases". U.S. Department of Agriculture, Agricultural Research Service. Retrieved October 6, 2018.
  20. ↑ Cole RS, Levitan D, Sinden RR (1976). "Removal of psoralen interstrand cross-links from DNA of Escherichia coli: mechanism and genetic control". J. Mol. Biol. 103 (1): 39–59. doi:10.1016/0022-2836(76)90051-6. PMID   785009.
  21. 1 2 Sinden RR, Cole RS (1978). "Repair of cross-linked DNA and survival of Escherichia coli treated with psoralen and light: effects of mutations influencing genetic recombination and DNA metabolism". J. Bacteriol. 136 (2): 538–47. doi:10.1128/JB.136.2.538-547.1978. PMC   218577 . PMID   361714.
  22. ↑ Saffran WA, Ahmed A, Binyaminov O, Gonzalez C, Gupta A, Fajardo MA, Kishun D, Nandram A, Reyes K, Scalercio K, Senior CW (2014). "Induction of direct repeat recombination by psoralen-DNA adducts in Saccharomyces cerevisiae: defects in DNA repair increase gene copy number variation". DNA Repair (Amst.). 21: 87–96. doi:10.1016/j.dnarep.2014.05.011. PMID   24969513.
  23. ↑ Hall JD (1982). "Repair of psoralen-induced crosslinks in cells multiply infected with SV40". Mol. Gen. Genet. 188 (1): 135–8. doi:10.1007/bf00333007. PMID   6294477. S2CID   5843939.
  24. ↑ Hall JD, Scherer K (1981). "Repair of psoralen-treated DNA by genetic recombination in human cells infected with herpes simplex virus". Cancer Res. 41 (12 Pt 1): 5033–8. PMID   6272987.
  25. ↑ Cimino GD, Gamper HB, Isaacs ST, Hearst JE (1985). "Psoralens as Photoactive Probes of Nucleic Acid Structure and Function: Organic Chemistry, Photochemistry, and Biochemistry". Annual Review of Biochemistry. 54: 1151–1193. doi:10.1146/annurev.bi.54.070185.005443. PMID   2411210.
  26. ↑ Lu Z, Zhang QC, Lee B, Flynn RA, Smith MA, Robinson JT, Davidovich C, Gooding AR, Goodrich KJ, Mattick JS, Messirov JP, Cech TR, Chang HY (2016). "RNA Duplex Map in Living Cells Reveals Higher-Order Transcriptome Structure". Cell. 165 (5): 1267–1279. doi:10.1016/j.cell.2016.04.028. PMC   5029792 . PMID   27180905.

Further reading

  1. Dean, F.M. (1963). Naturally Occurring Oxygen Ring Compounds . London: Butterworths.
  2. The Merck Index (7th ed.). Rahway NJ: Merck. 1960.
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