Genotoxic activity of some water-soluble derivatives of 5-methoxypsoralen and 8-methoxypsoralen.
This paper shows some results obtained by assaying the genotoxic activity on procaryotic and eucaryotic cells of some water-soluble psoralen derivatives. In particular, six newly synthesized derivatives of 5-methoxypsoralen (5-MOP) and of 8-methoxypsoralen (8-MOP) were tested; in previous studies they showed a strong anti-proliferative activity and a slight phototoxic effect; moreover, in view of a clinical use in the therapy of hyperproliferative skin diseases, these drugs should be less toxic than their parent compounds because of their good water solubility which could lead to a more efficient absorption and excretion. All the compounds tested here have shown genotoxic activity on both procaryotic and eucaryotic systems: however, on the procaryotic cells the water-soluble derivatives were less genotoxic than their respective parent compounds 5-MOP and 8-MOP. Quite different results were obtained on V79 Chinese hamster cells, showing that, in general, the 8-methoxy-derivatives are more mutagenic than the methoxy-ones, although the 5-MOP itself was shown to be highly genotoxic in this system. This fact confirms that a conclusive estimate of the genotoxic risk related to the use of new drugs cannot be drawn from the results obtained on a single biological system.
Tamaro
M
M
Gastaldi
S
S
Carlassare
F
F
Babudri
N
N
Pani
B
B
D000078223:5-Methoxypsoralen; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D008730:Methoxsalen / Q000633:toxicity*; D009152:Mutagenicity Tests; D010787:Photosensitivity Disorders; D012867:Skin / Q000187:drug effects; D012995:Solubility; D014867:Water
D014867:Water; D000078223:5-Methoxypsoralen; D008730:Methoxsalen