4,4',5'-trimethyl-8-azapsoralen, a new-photoreactive and non-skin-phototoxic bifunctional bioisoster of psoralen.
Photochemical and photobiological properties of a new isoster of psoralen, 4,4',5'-trimethyl-8-azapsoralen (4,4',5'-TMAP), have been studied. This compound shows a high DNA-photobinding rate, higher than that of 8-methoxypsoralen (8-MOP), forming both monoadducts and inter-strand cross-links. The yield of cross-links, however, is markedly lower than that of 8-MOP. Antiproliferative activity of 4,4',5'-TMAP, in terms of DNA synthesis inhibition in Ehrlich ascites tumor cells, is higher than that of 8-MOP. Mutagenic activity on E. coli WP2 R46+ cells appeared similar to or even lower than that of 8-MOP. This new compound applied on depilated guinea pig skin and irradiated with UVA did not show any skin-phototoxicity. On the basis of these properties 4,4',5'-TMAP appears to be a potential photochemotherapeutic agent.
Vedaldi
D
D
Department of Pharmaceutical Sciences, University of Padova, Italy.
Dall'Acqua
F
F
Caffieri
S
S
Baccichetti
F
F
Carlassare
F
F
Bordin
F
F
Chilin
A
A
Guiotto
A
A
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000503:physiopathology; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D004261:DNA Replication / Q000187:drug effects* / Q000528:radiation effects; D004926:Escherichia coli / Q000187:drug effects / Q000528:radiation effects; D011564:Furocoumarins / Q000138:chemical synthesis / Q000494:pharmacology*; D006168:Guinea Pigs; D051379:Mice; D009152:Mutagenicity Tests; D010100:Oxygen / Q000032:analysis; D010777:Photochemistry; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D026082:Singlet Oxygen; D012867:Skin / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects*; D014466:Ultraviolet Rays
D011564:Furocoumarins; D011838:Radiation-Sensitizing Agents; C067366:4,4',5'-trimethylazapsoralen; D026082:Singlet Oxygen; D004247:DNA; D010100:Oxygen