Some new methyl-8-methoxypsoralens: synthesis, photobinding to DNA, photobiological properties and molecular modelling.
The tricyclic structure of known natural photochemotherapeutic drugs such as 8-methoxypsoralen and 5-methoxypsoralen is often taken as a model in the search of new photosensitizer agents with less phototoxic and mutagenic effects. This paper describes the synthesis, characterization, photobinding to DNA, photobiological properties and computational chemistry of some 8-methoxypsoralen derivatives bearing two or three methyl groups at the key positions of the two photoactive double bonds. Results showed that photoreactivity and photobiological behaviour depend on the pattern of methyl substitutions. Antiproliferative activity in cell lines shows good correlation with DNA interaction data.
Gia
O
O
Department of Pharmaceutical Sciences, University of Padua, Italy.
Anselmo
A
A
Pozzan
A
A
Antonello
C
C
Magno
S M
SM
Uriarte
E
E
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004890:Erythema / Q000139:chemically induced; D006168:Guinea Pigs; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D008730:Methoxsalen / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D008958:Models, Molecular; D015394:Molecular Structure; D009010:Monte Carlo Method; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D012867:Skin / Q000187:drug effects; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D014407:Tumor Cells, Cultured
D017319:Photosensitizing Agents; D004247:DNA; D008730:Methoxsalen