5-(3-Phenylpropoxy)psoralen and 5-(4-phenylbutoxy)psoralen: mechanistic studies on phototoxicity.
5-(3-Phenylpropoxy)psoralen and 5-(4-phenylbutoxy)psoralen are blockers of the lymphocyte potassium channel Kv1.3 with EC50 values < 10 nM and may be used as new potential immunosuppressive drugs. As reported for many furocoumarins, these compounds show phototoxic properties and react under UV radiation with different targets in the cell, e.g. DNA or proteins and lipids in membranes. The photoreactions with these targets were investigated and compared to the well-known derivatives psoralen, 5-methoxypsoralen, 8-methoxypsoralen and 4,5',8-trimethylpsoralen. Moreover, absorption properties and the capability to photoproduce singlet oxygen (1O2) and reactive oxygen species (ROS) were studied. It was found that 5-(3-phenylpropoxy)psoralen and 5-(4-phenylbutoxy)psoralen are similar or less phototoxic in vitro as 5-methoxypsoralen which is the furocoumarin with the weakest phototoxicity in vivo compared to psoralen, 8-methoxypsoralen and 4,5',8-trimethylpsoralen.
Bode
C W
CW
Institute of Pharmacy, Department of Pharmaceutical Chemistry, Christian-Albrechts-University Kiel, Germany.
Hänsel
W
W
D000818:Animals; D003432:Cross-Linking Reagents; D004247:DNA / Q000737:chemistry; D017484:Dermatitis, Phototoxic / Q000473:pathology*; D004912:Erythrocytes / Q000187:drug effects / Q000528:radiation effects; D005363:Ficusin / Q000633:toxicity*; D005609:Free Radicals; D006461:Hemolysis; D066298:In Vitro Techniques; D051664:Kv1.3 Potassium Channel; D008055:Lipids / Q000737:chemistry; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D026902:Potassium Channel Blockers / Q000633:toxicity*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects; D011506:Proteins / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013481:Superoxides / Q000737:chemistry; D013552:Swine; D014466:Ultraviolet Rays
C499897:5-(3-Phenylpropoxy)psoralen; C499898:5-(4-phenylbutoxy)psoralen; D003432:Cross-Linking Reagents; D005609:Free Radicals; D051664:Kv1.3 Potassium Channel; D008055:Lipids; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D011506:Proteins; D013481:Superoxides; D004247:DNA; D005363:Ficusin; D010100:Oxygen