Phototoxicity psoralen

Diels-Alder reactions of benzo[fc]furan-43-diones and benzo[b]furan-4,7-diones have been reported <99H(50)1137>. The activation of a C-0 bond in a Mn(C0>3 complexed benzo[i>]furan was examined <99AG2343>. The enzyme-catalyzed dealkylation of (+)-marmesin to the phototoxic psoralene (and acetone) has been investigated <99AG413>. A hi yielding synthesis of bidentate bisoxazoline DBFOX/Ph [(R,R)-4,6-dibenzofutandiyl-2 2 -bis(4-phenyloxazoline)] was developed. DBFOX/Ph was subsequently tested in enantio-selective conjugate radical additions onto 3-(3-phenyl-2-propenoyl)-2-oxazolidinone <99TA2417>. 

A well-investigated group of potent phototoxic compounds are the/wra-nocoumarins (psoralens) (Fig. 11.16), compounds that are also used as fish poisons. Furocoumarins absorb ultraviolet at around 330 nm and are converted to triplet stages these, in turn, produce singlet oxygen that damages amino acids (Fig. 11.17). 

Injudicious use of the fruit of A. majus in combination with skin exposure to the sun can cause severe phototoxic dermatitis, owing to the presence of psoralens (6). 

L.D. Scheel, V.B. Perone, R.L. Larkin, R.E. Kupel (1963). The isolation and characterization of two phototoxic furanocoumarins (psoralens) from diseased celery. Biochemistry, 2,1127-1131. 

Photosensitizing and phototoxic chemicals found in more than two dozen plant sources, including celery, parsnips and parsley. Major compounds psoralen, methoxsalen, tri-oxsalen, bergapten and imperatorin. Stimulate melanocyte response to UV. 

Toxicological Implications for Man. Because psoralens are potent photoactive compounds, they have been used medically for treatment of skin de pigment at ion or vitiligo (16,17), and psoriasis (18). However, there has recently been concern associated with the medical use of these compounds (19). This concern is due to the observed phototoxicity during therapeutic use (17), the suspected photocarcinogenicity of xanthotoxin (20,21), and the latent onset of tumors in treated laboratory animals (22). Acute gout secondary to psoriasis also was exacerbated by psoralen and UV-A (PUVA) photochemotherapy (23). 

The mechanism of psoralen phototoxicity has been studied extensively, and 5-methoxy psoralen, which is only 0.33% of Bergamot oil, is believed to be the principal phototoxic component of the oil [190]. 5-Methoxy psoralen absorbs ultraviolet light above 310 millimicrons and is elevated to an excited state (free radical). The psoralen radicals link to pyrimidine bases... 

Averbeck, D., Recent advances in psoralen phototoxicity mechanism, Photochem. Photobiol,... 

The photochemical activity (phototoxicity) of several psoralen derivatives has potential appU-cation in several areas. Biotin derviative (340), for example, is a neoplasm inhibitor it inhibited the growth of lymphocytes by 99% in the presence of near UV light <87MIP8705805). Compounds (341) and (342) both displayed photochemical antibacterial activity <87Mi 208-04). Benzopsoralen (343) is a DNA photoreagent <86JHCI405). 

Zaynoun, S.T., B.E. Johnson, and W. Frain-BeU. 1977b. A study of oil of bergamot and its importance as a phototoxic agent. II. Factors which affect the phototoxic reaction induced by bergamot oil and psoralen derivatives. Contact Dermal. 3(5) 225-239. 

The most important drugs with sensitizing effects are listed in Table 4. Tetracyclines, in particular demethylchlortetracycline, are commonly responsible for photodermatitis. However, this action does not have any immunological basis, but depends on a phototoxic effect (Harder et al. 1961 Maibach et al. 1967), similar to that produced by psoralens, certain dyes, cadmium sulphide, etc. 

Table 1. Phototoxic plants containing furocoumarins (psoralens). Adapted from Pathek 1986 Pathak et al. (1962)...

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