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.
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.
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.
[10][11][12][13] 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.
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.
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.
[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.
Its structure prevents intercalation into DNA, and it only very weakly produces singlet oxygen, majorly reducing unwanted toxicity and mutagenicity in vivo.
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.
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).
[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.
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.
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.