Synthesis and photobiological properties of acetylpsoralen derivatives.
In an investigation to find monofunctional reactants for DNA which can act as new agents in the photochemotherapy of psoriasis, we have synthesized and studied some methylpsoralen derivatives which contain an acetyl group at one of the two reactive sites of the furocoumarin skeleton (at the 3 or 5' positions). The compounds do not react easily with DNA; their photobiological properties (e.g. the lack of an ability to inhibit DNA synthesis in Ehrlich ascites tumour cells, to induce T2 phage sensitization and to induce erythema in guinea-pig skin) are exactly in line with this behaviour. Some interesting features are shown by 4,8-dimethyl-5'-acetylpsoralen: it is capable of producing a very large amount of singlet oxygen--an order of magnitude higher than the other compounds and 8-methoxypsoralen (used as reference). In spite of this property, 4,8-dimethyl-5'-acetylpsoralen is non-phototoxic to the skin, and its other photobiological properties appear to be in line with its lack of interaction with DNA rather than its enhanced singlet oxygen production.
Carlassare
F
F
Department of Pharmaceutical Sciences, Padova University, Italy.
Baccichetti
F
F
Guiotto
A
A
Rodighiero
P
P
Gia
O
O
Capozzi
A
A
Pastorini
G
G
Bordin
F
F
D000107:Acetylation; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D004247:DNA / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004261:DNA Replication / Q000187:drug effects; D004307:Dose-Response Relationship, Radiation; D011564:Furocoumarins / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008730:Methoxsalen / Q000494:pharmacology; D051379:Mice; D010777:Photochemistry; D012867:Skin / Q000187:drug effects / Q000528:radiation effects; D013329:Structure-Activity Relationship; D014466:Ultraviolet Rays
D011564:Furocoumarins; D007202:Indicators and Reagents; D004247:DNA; D008730:Methoxsalen