Psoralens, angular

Because the resistance of polyxenes to the toxic effects of linear furanocoumarins apparently does not extend to the angular furanocoumarins (22), we have undertaken comparative metabolic fate studies with a representative of each of these furanocoumarin classes. Tritlated psoralen or isopsoralen (Figure 1) was administered as before to last stage polyxenes caterpillars, and the distribution, elimination, and biochemical fate of the compounds determined (28). 

The disposition patterns of psoralen and Isopsoralen in polyxenes under the parameters studied were not dramatically different. As Indicated in Table III, there were no appreciable differences in the rate of excretion of radioactivity by caterpillars treated with the two compounds. In body tissues, however, levels of total radioactivity in Isopsoralen-treated caterpillars were consistently about twice those observed in psoralen-treated insects (Table IV). Further, levels of unmetabolized parent compounds retained in body tissues (where toxic effects would be expressed) were on the order of 3 times as high in caterpillars treated with the angular furanocoumarin, isopsoralen (Table V). 

Figure 1. Structures of a linear furanocoumarin (psoralen) and an angular furanocoumarin (isopsoralen).

Only one class of benzofuran derivative, natural or synthetic, shows this property—the furocoumarins-, these are important for plant biosynthesis, since they take part in the elaboration of chlorophyll.308 13 Among linear furocoumarins, psoralene (27a) is particularly active. Angelicin (28), another fundamental furocoumarin heterocycle with an angular structure, has only about 12% of the photosensitizing activity of 27a.74-75 On the other hand, it has antibiotic activity. Furochromones have no photosensitizing properties. 

Viola, G., Racdolo, L., Vedaldi, D., Disaro, S., Basso, G. and Dall Acqua, R. (2004) Differential response of linear and angular psoralens in PUVA-induced apoptosis in HL-60 cells. Photochem. Photobiol. Sci., 3, 237-9. 

The treatment of the allyl derivative with ozone has been advantageously replaced by the osmium tetroxide-KIO method psoralene has thus been made from a 7-acetoxy-6-alkylcoumarin and xanthotoxin, angelicin (28), and dehydrodemethoxyelliptone (114)3i3([ijbenzopyrano[3,4-6]furo[2,3-fe][l]benzopyran-6-one),thefuro-flavones and furoisoflavones, khellin (26), the angular furoxan-thone (115), and bergaptene (4-methoxypsoralene) have all been synthesized. 

The linear (psoralens) and angular (angelicins) fur-anocoumarins can be readily differentiated with the Emerson reagent. It is used, also, for detection of pyrano-coumarins (selinidin, pteryxin) on TLC chromatograms. 

In the final chapter, Gambari et aL summarize the structure and biological effects of furocoumarins. The authors mainly focus on linear and angular psoralens. Borrowing from their laboratory experiences, they describe the interesting biological effects of such compounds on cell cycle, apoptosis and differentiation as well as their use for the treatment of j6-thalassemia. 

The conclusion of this review is that linear and angular psoralens [l-ll, 58, 59] exhibit very interesting biological effects on eukaryotic cells and should be considered as promising drugs in the therapy of several diseases, including psoriasis, mycosis fungoides, cancer. 

Coumarins are lactones with the basic structure of 1,2-benzopyrone. Biosynthetically, they are mainly originated from shikimic acid padiway, with the intermediate of cinnamic acid. By the addition of a furan ring, the furanocoumarins are resulted, which are represented by psoralen (linear) and angelicin (angular) [10]. 

Prenylation at C-6 and C-8 can lead to linear coumarins, such as psoralen (2), and xanthyletin (3), or angular forms, like angelicin (4) and seselin (5), respectively. In this regard, coumarins are classified as following [8] ... 

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