Trioxsalen

Last updated
Trioxsalen
Trioxsalen.png
Names
Preferred IUPAC name
2,5,9-Trimethyl-7H-furo[3,2-g][1]benzopyran-7-one
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.021.327 OOjs UI icon edit-ltr-progressive.svg
KEGG
PubChem CID
UNII
  • InChI=1S/C14H12O3/c1-7-4-12(15)17-14-9(3)13-10(6-11(7)14)5-8(2)16-13/h4-6H,1-3H3 Yes check.svgY
    Key: FMHHVULEAZTJMA-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C14H12O3/c1-7-4-12(15)17-14-9(3)13-10(6-11(7)14)5-8(2)16-13/h4-6H,1-3H3
    Key: FMHHVULEAZTJMA-UHFFFAOYAF
  • Cc1cc2c(o1)c(C)c1c(c2)c(C)cc(=O)o1
Properties
C14H12O3
Molar mass 228.24328
Pharmacology
D05AD01 ( WHO ) D05BA01 ( WHO )
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

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 [1] and hand eczema. [2] 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. [3] 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. [4]

Trioxsalen (abbreviated as TMP) activated by UV-A exposure is commonly used in genetics research as an experimental mutagen. UV/TMP generates small deletions (~1-3 Kbp), but all base transitions and transversions can also be obtained. [5]

Related Research Articles

Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, research, and forensics. Commonly made in the laboratory by solid-phase chemical synthesis, these small bits of nucleic acids can be manufactured as single-stranded molecules with any user-specified sequence, and so are vital for artificial gene synthesis, polymerase chain reaction (PCR), DNA sequencing, molecular cloning and as molecular probes. In nature, oligonucleotides are usually found as small RNA molecules that function in the regulation of gene expression, or are degradation intermediates derived from the breakdown of larger nucleic acid molecules.

Gene knockdown is an experimental technique by which the expression of one or more of an organism's genes is reduced. The reduction can occur either through genetic modification or by treatment with a reagent such as a short DNA or RNA oligonucleotide that has a sequence complementary to either gene or an mRNA transcript.

Locked nucleic acid Biological molecule

A locked nucleic acid (LNA), also known as bridged nucleic acid (BNA), and often referred to as inaccessible RNA, is a modified RNA nucleotide in which the ribose moiety is modified with an extra bridge connecting the 2' oxygen and 4' carbon. The bridge "locks" the ribose in the 3'-endo (North) conformation, which is often found in the A-form duplexes. This structure can be attributed to the increased stability against enzymatic degradation; moreover the structure of LNA has improved specificity and affinity as a monomer or a constituent of an oligonucleotide. LNA nucleotides can be mixed with DNA or RNA residues in the oligonucleotide, in effect hybridizing with DNA or RNA according to Watson-Crick base-pairing rules.

Morpholino Chemical compound

A Morpholino, also known as a Morpholino oligomer and as a phosphorodiamidate Morpholino oligomer (PMO), is a type of oligomer molecule used in molecular biology to modify gene expression. Its molecular structure contains DNA bases attached to a backbone of methylenemorpholine rings linked through phosphorodiamidate groups. Morpholinos block access of other molecules to small specific sequences of the base-pairing surfaces of ribonucleic acid (RNA). Morpholinos are used as research tools for reverse genetics by knocking down gene function.

Antisense RNA

Antisense RNA (asRNA), also referred to as antisense transcript, natural antisense transcript (NAT) or antisense oligonucleotide, is a single stranded RNA that is complementary to a protein coding messenger RNA (mRNA) with which it hybridizes, and thereby blocks its translation into protein. asRNAs have been found in both prokaryotes and eukaryotes, and can be classified into short and long non-coding RNAs (ncRNAs). The primary function of asRNA is regulating gene expression. asRNAs may also be produced synthetically and have found wide spread use as research tools for gene knockdown. They may also have therapeutic applications.

Sulfamethoxazole

Sulfamethoxazole is an antibiotic. It is used for bacterial infections such as urinary tract infections, bronchitis, and prostatitis and is effective against both gram negative and positive bacteria such as Listeria monocytogenes and E. coli.

PUVA is an ultraviolet light therapy treatment for skin diseases: eczema, psoriasis, graft-versus-host disease, vitiligo, 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.

Nitrogen mustard Family of chemical compounds

Nitrogen mustards are cytotoxic organic compounds with the chloroethylamine (Cl(CH2)2NR2) 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.

Psoralen Chemical compound

Psoralen 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 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.

DNA polymerase II

DNA polymerase II is a prokaryotic DNA-Dependent DNA polymerase encoded by the PolB gene.

Altretamine

Altretamine, also called hexamethylmelamine, is an antineoplastic agent. It was approved by the U.S. FDA in 1990.

In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complement in specifying a sequence of amino acids. Depending on the context, sense may have slightly different meanings. For example, negative-sense strand of DNA is equivalent to the template strand, whereas the positive-sense strand is the non-template strand whose nucleotide sequence is equivalent to the sequence of the mRNA transcript.

Crosslinking of DNA

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.

Computational gene

A computational gene is a molecular automaton consisting of a structural part and a functional part; and its design is such that it might work in a cellular environment.

Mipomersen Drug used to treat genetic hypercholesterolemia

Mipomersen is a drug used to treat homozygous familial hypercholesterolemia and is administered by subcutaneous injection. There is a serious risk of liver damage from this drug and it can only be prescribed in the context of a risk management plan.

Angelicin 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 coumarine.

DNA polymerase nu

Polymerase nu is a protein in humans that is encoded by the POLN gene. It is a family A DNA polymerase, considered to be the least effective of the polymerase enzymes. However, DNA polymerase nu plays an active role in homology repair during cellular responses to crosslinks, fulfilling its role in a complex with helicase.

Transcriptome in vivo analysis tag

A transcriptome in vivo analysis tag is a multifunctional, photoactivatable mRNA-capture molecule designed for isolating mRNA from a single cell in complex tissues.

A hybridization assay comprises any form of quantifiable hybridization i.e. the quantitative annealing of two complementary strands of nucleic acids, known as nucleic acid hybridization.

Toshifumi (Toshi) Yokota is a medical scientist and professor of medical genetics at the University of Alberta, where he also holds the Friends of Garrett Cumming Research & Muscular Dystrophy Canada Endowed Research Chair and the Henri M. Toupin Chair in Neurological Science. He is best known for his studies of antisense oligonucleotide-based therapeutics for muscular dystrophy that led to the development of an FDA-approved drug viltolarsen. His research interests include precision medicine for muscular dystrophy and genetic diseases. He has co-edited two books both published in the Methods in Molecular Biology series from Humana Press, Springer-Nature, and has published more than 100 refereed papers and patents. He is a member of the editorial boards for the International Journal of Molecular Sciences, Genes, Frontiers in Genome Editing, and Nucleic Acid Therapeutics a member of the Medical and Scientific Advisory Committee of Muscular Dystrophy Canada, and a co-founder of the Canadian Neuromuscular Network (CAN-NMD).

References

  1. "Trioxsalen - Compound Summary". PubChem.
  2. Van Coevorden, AM; Kamphof, WG; Van Sonderen, E; Bruynzeel, DP; Coenraads, PJ (2004). "Comparison of oral psoralen-UV-A with a portable tanning unit at home vs hospital-administered bath psoralen-UV-A in patients with chronic hand eczema: an open-label randomized controlled trial of efficacy". Archives of Dermatology. 140 (12): 1463–6. doi: 10.1001/archderm.140.12.1463 . PMID   15611423.
  3. Thazhathveetil, AK; Liu, ST; Indig, FE; Seidman, MM (2007). "Psoralen conjugates for visualization of genomic interstrand cross-links localized by laser photoactivation". Bioconjugate Chemistry. 18 (2): 431–7. doi:10.1021/bc060309t. PMID   17373769.
  4. Higuchi, M; Yamayoshi, A; Kobori, A; Yamaoka, T; Murakami, A (2005). "Synthesis and properties of photo-reactive antisense oligonucleotides containing 2'-O-psoralen-conjugated adenosine". Nucleic Acids Symposium Series. 49 (49): 331–2. doi: 10.1093/nass/49.1.331 . PMID   17150768.
  5. Kutscher, Lena M.; Shaham, Shai (2014). "Forward and reverse mutagenesis in C. elegans". WormBook: The Online Review of C. Elegans Biology: 1–26. doi:10.1895/wormbook.1.167.1. PMC   4078664 . PMID   24449699 . Retrieved 18 June 2021.