Photochemical and photobiological properties of 4,5'-dimethylpsoralen, a bifunctional contaminant of synthetic 4,5'-dimethylangelicin.
4,5'-Dimethylpsoralen, a bifunctional furocoumarin, can be formed as an impurity in the synthesis of its angular isomer, that is 4,5'-dimethylangelicin; the latter has recently been proposed as a potential monofunctional agent for photochemotherapy. To have precise information on the possible modifications of the photochemical and photobiological properties of synthetic 4,5'-dimethylangelicin caused by the presence of its linear isomer, we have studied the interactions of the latter with DNA in both the ground and the excited state and its photobiological activity. 4,5'-Dimethylpsoralen photobinds much more effectively to DNA than its angular isomer and is capable to form effectively inter-strand cross-linkages in DNA while dimethylangelicin is unable to form these bifunctional adducts in DNA. Dimethylpsoralen shows a strong skin-phototoxicity while angelicin lacks this activity. Moreover the antiproliferative activity of the psoralen derivative in terms of DNA synthesis inhibition in Ehrlich cells and of inhibition of infectivity of T2 phages, is about four times higher than that of the angular isomer. These data stress the necessity of the absence of the isomeric linear furocoumarin in the synthetic 4,5'-dimethylangelicin because its presence can markedly modify the photobiological and phototherapeutic properties of the angelicin derivative.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000378:metabolism / Q000528:radiation effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D003956:Dialysis; D011564:Furocoumarins / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D010777:Photochemistry; D010787:Photosensitivity Disorders / Q000139:chemically induced; D012334:RNA, Neoplasm / Q000096:biosynthesis; D013604:T-Phages / Q000187:drug effects
D004273:DNA, Neoplasm; D011564:Furocoumarins; D012334:RNA, Neoplasm; C031828:4,5-dimethylpsoralen; C021665:4,5'-dimethylangelicin; D004247:DNA