4'-Methylangelicin derivatives: a new group of highly photosensitizing monofunctional furocoumarins.
The photobiological properties of three new angelicin derivatives carrying a methyl-group in 4' position at the furanic ring have been studied. In double-irradiation experiments on E. coli cells, they appeared to behave as monofunctional reactives towards DNA, similarly to the other angelicin derivatives previously studied. In short-term experiments such as the studies on macromolecular synthesis in Ehrlich ascites cells, in which the assay is performed that after irradiation, before DNA repair an intervene significantly, 4'-methylangelicin derivatives produced an inhibition of DNA and RNA synthesis 10 times higher than angelicin, the parent compound, and about 3.5 times higher than 4,5'-dimethylangelicin and psoralen, all assumed as reference compounds. In long-term experiments such as the studies on tumor transmission to healthy mice by injection of sensitized Ehrlich ascites cells, or on the survival of E. coli cells, in which DNA repair is active, 4'-methylangelicin derivatives appeared to be several times more active than angelicin and 4,5'-dimethylangelicin, and sometimes also more active than psoralen, a well-known, effective and cross-linking furocoumarin. While, as already observed, angelicin and 4,5'-dimethylangelicin failed to induce erythema on guinea-pig skin, 4'-methylangelicin derivatives proved to be phototoxic; however in comparison with the cross-linking psoralen, much higher amounts of substance and radiation doses were required. The erythema produced by 4'-methylangelicin derivatives presents some typical features of cross-linking furocoumarins, such as a long latency period and insensitivity to the anti-inflammatory drugs.
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000503:physiopathology; D055598:Chemical Phenomena; D002621:Chemistry; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004926:Escherichia coli / Q000187:drug effects; D011564:Furocoumarins / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D010787:Photosensitivity Disorders / Q000139:chemically induced; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014466:Ultraviolet Rays
D004273:DNA, Neoplasm; D011564:Furocoumarins; D012334:RNA, Neoplasm; C031824:4-methylangelicin