298-81-7 Usage
Description
Different sources of media describe the Description of 298-81-7 differently. You can refer to the following data:
1. 8-methoxypsoralen (also known as methoxsalen) is a naturally occurring furocoumarin compound existing in several species of plants such as Psoralea corylifolia. It is a photoactive substance that can form DNA adducts upon UVA irradiation. It is a drug used for the treatment of psoriasis, eczema, vitiligo, and some kinds of cutaneous lymphomas associated with the exposure of skin to the UVA or light from lamps or sunlight. Its mechanism of action is through inhibiting the synthesis of the deoxyribonucleic acid (DNA). After the activation, it can preferentially bind to the guanine and cytosine molecules of DNA, further leading to the cross-linking of DNA, thus inhibiting the DNA synthesis. It can further inhibit the RNA and protein synthesis at high concentration. It is extracted from Ammi majus.
2. 8-Methoxypsoralen (8-MOP) and other psoralens are naturally
found in plants, including common fruit and vegetable crops.
References
https://www.drugbank.ca/drugs/DB00553
https://en.wikipedia.org/wiki/Methoxsalen
Chemical Properties
White to cream-colored, crystalline
solid; odorless. Slightly soluble in alcohol; practically insoluble in water. Combustible.
Originator
Oxsoracen,Eider,US,1955
Uses
Different sources of media describe the Uses of 298-81-7 differently. You can refer to the following data:
1. 8-Methoxypsoralen, is used in Photochemotherapy (methoxsalen with long wave ultraviolet radiation) is indicated for the repigmentation of idiopathic vitiligo. It is also used in Photopheresis (methoxsalen with long wave ultraviolet radiation of white blood cells) is indicated for use with the UVAR* System in the palliative treatment of the skin manifestations of cutaneous T-cell lymphoma.
2. antipsoriatic, pigmentation agent
3. Naturally occurring analog of Psoralen (P839800). Use in treatment of psoriasis and mycosis fungoides.
4. For the treatment of psoriasis and vitiligo
5. A potent suicide inhibitor of cytochrome P-450.
6. Naturally occurring analog of psoralen. Use in treatment of psoriasis and mycosis fungoides
Indications
Methoxsalen has effects similar to those of trioxsalen. Methoxsalen is superior
to trioxsalen in producing erythema and tanning and is the drug used in PUVA
therapy. Methoxsalen is also available as a 1% lotion.
Definition
ChEBI: A member of the class of psoralens that is 7H-furo[3,2-g]chromen-7-one in which the 9 position is substituted by a methoxy group. It is a constituent of the fruits of Ammi majus. Like other psoralens, trioxsalen
causes photosensitization of the skin. It is administered topically or orally in conjunction with UV-A for phototherapy treatment of vitiligo and severe psoriasis.
Manufacturing Process
It has been found that the compound 8-geranoxy psoralen is present in citrus
oils, particularly lemon and lime oils. This compound can be isolated from the
oil by a process which involves primarily absorption on an adsorbent material
followed by elution with a suitable solvent.
(A) Cleavage of 8-Geranoxypsoralen: 275 mg of 8-geranoxypsoralen was
dissolved with mechanical stirring in 4 ml glacial acetic acid. After 10 minutes,one drop of concentrated sulfuric acid was added to the solution. In 4 minutes
thereafter a light tan precipitate began to form. Stirring was continued for 35
minutes and the reaction mixture was refrigerated for one hour and 20
minutes. The precipitate was then removed by suction filtration and washed
on the filter with glacial acetic acid followed by ice-cold ethyl ether. The
product, 8-hydroxypsoralen, weighed 115 mg, that is, 74% of theory.
(B) Methylation of 8-Hydroxypsoralen: 115 mg of 8-hydroxypsoralen was
dissolved in 10 ml absolute methanol, an excess of diazomethane dissolved in
ether was added and the mixture allowed to stand at room temperature with
occasional stirring for 3 hours. The next day the reaction mixture was reduced
in volume to 3 ml by evaporation on the steam bath and the concentrate was
held in a refrigerator overnight. The next day, fine needles (80 mg) of 8-
methoxypsoralen were filtered from the solution. The compound had a MP of
145 to 146°C and was obtained in a yield of 65% of theory.
There is also a wholly synthetic route to Methoxsalen as outlined by Kleeman
and Engel.
Brand name
8-Mop (Valeant); Oxsoralen (Valeant); Uvadex (Therakos).
Therapeutic Function
Dermal pigmentation enhancer
General Description
Odorless white to cream-colored crystalline solid. Bitter taste followed by tingling sensation.
Air & Water Reactions
Sensitive to light and air. Insoluble in water.
Reactivity Profile
8-Methoxypsoralen is incompatible with strong oxidizing agents.
Fire Hazard
Flash point data for 8-Methoxypsoralen are not available; however, 8-Methoxypsoralen is probably combustible.
Contact allergens
This fur(an)ocoumarin is an phototoxic compound
that causes phototoxic dermatitis. Many plants of the
Apiaceae–Umbelliferae and most of the Rutaceae family
contain 5-methoxypsoralen and 8-methoxypsoralen.
Their spectra is in the UVA range (300–360 nm). It is
used in combination with UVA to treat various skin
disorders such as psoriasis.
Safety Profile
Confirmed carcinogen.
Poison by intraperitoneal route. Moderately
toxic by ingestion and subcutaneous routes.
Human mutation data reported. When
heated to decomposition it emits acrid
smoke and irritating fumes. A drug used to
treat slun diseases.
Environmental Fate
The industrial use of 8-MOP results in its release into the
environment through multiple pathways, and its existence as
a natural substance in plants further expands exposure to the
environment. Airborne 8-MOP will exist in the vapor and
particulate phases, and will be degraded in air by reaction with
photochemically produced hydroxyl radicals, with an estimated
half-life of approximately 1.2 h, it may also be subject to
direct photolysis by sunlight. Particulate 8-MOP will be
removed from the atmosphere by wet or dry deposition. If
released into the soil, it is expected to have high mobility and is
not expected to volatilize. 8-MOP does not biodegrade. In
aqueous environments, 8-MOP is not expected to hydrolyze, it
will, however, adsorb to suspended solids and sediment. Due
to 8-MOP’Ks resistance to degradation by many routes, it is
expected to remain in the environment for a prolonged period,
and as such will also be subject to long-range transport. 8-MOP
has an estimated bioconcentration factor (BCF) of 9, meaning
that bioconcentration and bioaccumulation are low in aquatic
organisms.
Purification Methods
Purify xanthotoxin by recrystallisation from *C6H6/pet ether (b 60-80o) to give silky needles, or from EtOH/Et2O to give rhombic prisms or from hot H2O to give needles. It is soluble in aqueous alkali due to ring opening of the cyclic lactone but recyclises upon acidification. It has UV max in EtOH at 219, 249 and 300nm (log 4.32, 4.35 and 4.06) and 1H NMR in CDCl3 with at 7.76 (d, 1H, J 10 Hz), 7.71 (d, 1H, J 2.5 Hz), 7.38 (s, 1H), 6.84 (d, 1H, J 2.5 Hz), 6.39 (d, 1H, J 10 Hz) and 4.28 (s, 3H)ppm. [Nore & Honkanen J Heterocycl Chem 17 985 1980.] It is a DNA intercalator, is used in the treatment of dermal diseases, and is a human carcinogen [Tessman et al. Biochemistry 24 1669 1985.] [Beilstein 19 I 711, 19/6 V 15.]
Toxicity evaluation
The toxic effects of psoralens almost never occur without
exposure to UV light. These are photosensitizing materials that
exert their primary effect on the skin. 8-MOP, when activated
by long-wavelength UV light in the range of 320–400 nm, is
strongly erythemogenic, melanogenic, and cytotoxic in the
epidermis. The mechanisms of action of 8-MOP in inducing
repigmentation of vitiliginous skin have not been established.
Repigmentation depends on the presence of functioning
melanocytes and UV light. 8-MOP may activate the functional
and dihydroxyphenylalanine-positive melanocytes present in
vitiliginous skin. An increase in the activity of tyrosinase, the
enzyme that catalyzes the conversion of tyrosine to dihydroxyphenylalanine
(a precursor of melanin), has been shown in melanin-producing cells exposed in vitro to trioxsalen and UVA
light. In addition, binding of photoactivated psoralens (in
triplet states) to pyrimidine bases of nucleic acids, with
subsequent inhibitions of DNA synthesis, cell division, and
epidermal turnover, has been demonstrated. Following photoactivation,
8-MOP forms covalent bonds with DNA to
produce monofunctional (addition to a single strand of DNA)
and bifunctional adducts (cross-linking to both strands of
DNA). Reactions with other proteins also occur. Psoralens may
also increase melanin formation by producing an inflammatory
reaction in the skin. Other mechanisms of increased
pigmentation may include an increase in the number of functional
melanocytes (and possibly activation of dormant
melanocytes); enhancement of melanin granule synthesis;
stimulation of the movement of melanocytes up hair follicles
resulting in melanocytic repopulation of the epidermis; and/or
hypertrophy of melanocytes and increased arborization of their
dendrites. Since psoriasis is a hyperproliferative disorder and
other agents effective in the treatment of psoriasis are known to
inhibit DNA synthesis, the therapeutic effect of 8-MOP in the
treatment of psoriasis probably involves binding to DNA and
inhibition of DNA synthesis resulting in decreased cell proliferation;
other vascular, leukocyte, or cell regulatory mechanisms
may be involved. It has been suggested that at low drug
load, 8-MOP binds to DNA as an intercalator, whereas at higher
ratios of 8-MOP to DNA, it binds to the outside of DNA,
probably in the minor groove and causes some compaction in
DNA. Protective eyewear is used to prevent irreversible binding
of 8-MOP to proteins and DNA components of the lens. The
central hypothesis for the reproductive toxicity of 8-MOP is
that it produces reproductive effects by disrupting the hypothalamus–
pituitary axis, and the alternative hypothesis is that
this compound targets gonadal function, resulting in alteration
of pregnancy outcome.
Check Digit Verification of cas no
The CAS Registry Mumber 298-81-7 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 2,9 and 8 respectively; the second part has 2 digits, 8 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 298-81:
(5*2)+(4*9)+(3*8)+(2*8)+(1*1)=87
87 % 10 = 7
So 298-81-7 is a valid CAS Registry Number.
InChI:InChI=1/C12H8O4/c1-14-12-10-8(4-5-15-10)6-7-2-3-9(13)16-11(7)12/h2-6H,1H3
298-81-7Relevant articles and documents
8-Methoxypsoralen-Nucleic Acid Photoreaction. Effect of Methyl Substitution on Pyrone vs. Furan Photoaddition
Kanne, David,Rapoport, Henry,Hearst, John E.
, p. 531 - 534 (1984)
We have synthesized a series of 8-methoxypsoralens in which methyl and hydrogen are systematically varied at the 4- and 5'-positions.Analysis of the products resulting from the photoaddition of these four psoralens with the nucleic acid poly(dA-dT) reveals that the product distribution depends on the presence or absence of a 4-methyl substituent.Compounds with the 4-methyl group show an overwhelming preference (ca.98percent) for addition to the furan double bond, while compounds without the 4-methyl show a substantial amount (ca.18percent) of addition to the pyrone double bond.
Electronic Finetuning of 8-Methoxy Psoralens by Palladium-Catalyzed Coupling: Acidochromicity and Solvatochromicity
Geenen, Sarah R.,Presser, Lysander,H?lzel, Torsten,Ganter, Christian,Müller, Thomas J. J.
supporting information, p. 8064 - 8075 (2020/06/02)
Differently 5-substituted 8-methoxypsoralens can be synthesized by an efficient synthetic route with various cross-coupling methodologies, such as Suzuki, Sonogashira and Heck reaction. Compared to previously synthesized psoralens, thereby promising daylight absorbing compounds as potentially active agents against certain skin diseases can be readily accessed. Extensive investigations of all synthesized psoralen derivatives reveal fluorescence in the solid state as well as several distinctly emissive derivatives in solution. Donor-substituted psoralens exhibit remarkable photophysical properties, such as high fluorescence quantum yields and pronounced emission solvatochromicity and acidochromicity, which were scrutinized by Lippert–Mataga and Stern–Volmer plots. The results indicate that the compounds exceed the limit of visible light, a significant factor for potential applications as an active agent. In addition, (TD)DFT calculations were performed to elucidate the underlying electronic structure and to assign experimentally obtained data.
Synthesis and evaluation of linear furanocoumarins as potential anti-breast and anti-prostate cancer agents
Chauthe, Siddheshwar K.,Mahajan, Shivani,Rachamalla, Mahesh,Tikoo, Kulbhushan,Singh, Inder P.
, p. 2476 - 2484 (2015/02/19)
A series of 22 furanocoumarin derivatives were synthesized and evaluated for cytotoxicity against breast cancer (MCF-7 and MDA-MB-231) and prostate cancer (PC-3) cell lines along with normal cell line. Several analogs were synthesized by replacing prenyl moiety with alkyl, aromatic, and heteroaromatic functionality to study the structure-activity relationship. Compounds 20 and 22 with adamantoylamino, diprenylamino and substituted benzene sulfonamide substituents showed potent antiproliferative activity in MCF-7 cell line with IC50 values of 0.48 and 0.53 μM, respectively. Both the compounds showed higher IC50 value in MCF-10A cell lines indicating nontoxicity in normal cell lines.
CINAMIC COMPOUNDS AND DERIVATIVES THEREFROM FOR THE INHIBITION OF HISTONE DEACETYLASE
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Page/Page column 22-23, (2010/10/19)
The invention relates to a compound represented by the following formula (I): and pharmaceutically acceptable salts, stereoisomers, enantiomers, prodrugs and solvates thereof. The compounds are useful as an agent for enhancing the neurite outgrowth and preventing or treating of diseases associated with HDAC in particular, tumor or cell proliferative diseases. In particular, the compounds of the invention can be used as an agent for anti-cancer, anti-diabetic, and anti-neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, Spinocerebellar Ataxias (SCA), and human spinal muscular atrophy (SMA).
