Synthesis and photobiological activity of new methylpsoralen derivatives.
The synthesis and the photobiological activity of two new derivatives of psoralen (3,4'-dimethylpsoralen and 3,4',8-trimethylpsoralen) has been described. They are congeners of the monofunctional linear furocoumarin 3,4'-dimethyl-8-methoxypsoralen. Both compounds bind very efficiently to DNA, the extent of this process being modulated by the nature of substituents at position 8. The number of photolesions is linearly related to adenine-thymine content of the nucleic acid which indicates lack of specificity for particular sequences of the nucleic acid. The structural arrangement of DNA (single stranded, double stranded, nucleosomes and chromatin) plays an additional role in affecting the photobinding process. Unlike their 8-methoxy congener the new derivatives cross-link DNA to a substantial extent. Their photobiological properties, including erythema formation, reflect very closely those of 8-methoxypsoralen (8-MOP). The conclusion can be drawn that 3,4'-dimethyl-8-MOP represents a unique derivative in its family.
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Department of Pharmaceutical Sciences, Padua University, Italy.
Uriarte
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E
Zagotto
G
G
Baccichetti
F
F
Antonello
C
C
Marciani-Magno
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S
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004261:DNA Replication / Q000187:drug effects*; D004307:Dose-Response Relationship, Radiation; D011564:Furocoumarins / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D006168:Guinea Pigs; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008730:Methoxsalen / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D008968:Molecular Conformation; D011838:Radiation-Sensitizing Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D012867:Skin / Q000187:drug effects* / Q000528:radiation effects; D014466:Ultraviolet Rays
D011564:Furocoumarins; D007202:Indicators and Reagents; D011838:Radiation-Sensitizing Agents; D004247:DNA; D008730:Methoxsalen