Khellin, a naturally occurring furochromone, used for the photochemotherapy of skin diseases: mechanism of action.
Khellin, a naturally occurring furochromone, used in the past as a coronary vasodilator, has recently been used in the photochemotherapeutic treatment of vitiligo and psoriasis. With the aim of elucidating its mechanism of action, the interactions both in ground and excited states between the drug and DNA were studied in vitro. Khellin forms in the dark a molecular complex with DNA. By subsequent irradiation (365 nm) the drug photoconjugates covalently with the macromolecule, although the rate of photobinding is rather low. The in vivo photobinding of khellin to the DNA of Ehrlich ascites tumor cells is also low. In photoaddition with the macromolecule the drug forms inter-strand cross-links, although again in small amounts. The furan side monoadduct between khellin and thymine, formed in the photoreaction between the drug and DNA, was isolated and characterized, and shows a cis-syn configuration.
Vedaldi
D
D
Department of Pharmaceutical Sciences, University of Padua, Italy.
Caffieri
S
S
Dall'Acqua
F
F
Andreassi
L
L
Bovalini
L
L
Martelli
P
P
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D003432:Cross-Linking Reagents; D004247:DNA / Q000378:metabolism / Q000528:radiation effects; D003956:Dialysis; D007666:Khellin / Q000032:analysis* / Q000378:metabolism / Q000627:therapeutic use; D008730:Methoxsalen / Q000032:analysis / Q000528:radiation effects; D010777:Photochemistry; D012871:Skin Diseases / Q000188:drug therapy; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet
D003432:Cross-Linking Reagents; D007666:Khellin; D004247:DNA; D008730:Methoxsalen