Some photochemical and photobiological properties of 8,8-desmethylxanthyletine (homopsoralen), a potential photochemotherapeutic agent.
In this paper the photochemical and photobiological properties of 8,8-desmethyl-xanthyletine (homopsoralen) have been studied. This drug forms a molecular complex with DNA undergoing intercalation between two base pairs of the macromolecule. By subsequent irradiation (365 nm) the compound photobinds covalently to the macromolecule showing an initial DNA-photobinding rate higher than that of 8-methoxypsoralen. In the photoreaction with DNA the drug effectively forms inter-strand cross-linkages. Its ability to generate singlet oxygen when irradiated with ultraviolet light is markedly higher than that of 8-MOP. Homopsoralen when irradiated in water solution undergoes effective photolysis. The drug shows a lower antiproliferative activity on diploid yeast (D 7) than 8-MOP and an almost parallel mutagenic activity. Also the gene convertogenic activity, determined on the same yeast strain, is lower than that of 8-MOP. Homopsoralen does not show any skin phototoxicity on guinea-pig skin. Taking into account its DNA-photobinding capacity, its antiproliferative activity, its reduced genotoxicity and lack of skin-phototoxicity homopsoralen may deserve further studies for evaluating its photochemotherapeutic activity.
Vedaldi
D
D
Department of Pharmaceutical Sciences of the University, Padova, Italy.
Dall'Acqua
F
F
Averbeck
D
D
Cundari
E
E
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000187:drug effects; D011564:Furocoumarins / Q000032:analysis / Q000494:pharmacology* / Q000528:radiation effects; D005785:Gene Conversion / Q000187:drug effects; D006168:Guinea Pigs; D008027:Light; D009153:Mutagens; D010100:Oxygen / Q000032:analysis; D010778:Photochemotherapy; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics; D012867:Skin / Q000187:drug effects
D011564:Furocoumarins; D009153:Mutagens; C058611:homopsoralen; D004247:DNA; D010100:Oxygen