The photostability of quercetin in alcoholic solutions was studied. Both UVA and UVB light induced degradation of quercetin, yielding a single product 1 deriving from oxidation and addition of an alcohol molecule to the 2,3 double bond. The same mechanism operated when quercetin was dissolved in alkaline solutions, and again a product 2 due to oxidation and addition of water was characterized. Comparison with quercetin analogs confirmed that, despite the presence of five hydroxy groups in quercetin, those in positions 3, 3′, and 4′ are mainly involved in the antioxidant activity of the compound , as well as in its photolability.

The mechanism of cell death was investigated in Jurkat cells exposed to the combination of psoralen and UVA irradiation (PUVA). Apoptosis was by far prevailing over necrosis and involved mitochondrial dysfunction. The collapse of mitochondrial membrane potential, appears to be caused by the opening of the mitochondrial permeability transition pore since its inhibitor, cyclosporin A, prevented mitochondrial dysfunction and largely attenuated apoptosis. Apoptosis also occurred in cells treated with the photoproducts generated by irradiating psoralen in vitro with an oxygen-dependent process. Thus, the involvement of reactive oxygen species in the onset of PUVAinduced apoptosis appears mostly related to psoralen photooxidation. ß 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

Furocoumarins (psoralens) undergo photolysis when subjected to UVA radiation in solution. Several products are formed, depending on the molecular structure and experimental conditions. Some products are the result of anoxic mechanisms (cyclodimerisation, addition of solvent), others of oxic pathways, leading to oxidised products. The mechanisms thought to underlie photolysis are described and the possible biological relevance of the photoproducts and intermediates is discussed.

The synthesis and photobiological activity of four new 4'-methyl derivatives of 5-MOP (5-methoxypsoralen) and 5-MOA (5-methoxyangelicin), i.e., 4,4'-dimethyl-5-methoxypsoralen, 3,4'-dimethyl-5-methoxypsoralen, 4,4'-dimethyl-5-methoxyangelicin, and 3,4'-dimethyl-5-methoxyangelicin, are described. All these compounds photobind efficiently to DNA. The DNA-photobinding process was investigated using various nucleic acid structures such as double-helix DNA, bacterial DNA, and synthetic polydeoxyribonucleotides. Photoreaction experiments showed that, unlike 8-MOP (8-methoxypsoralen) and 5-MOP, both angular derivatives bind thymine and cytosine with the same efficiency. The principal nucleoside-psoralen monoadducts were isolated and characterized after enzymatic digestion or acid hydrolysis. Biological activity studies revealed a good correlation with the extent of covalent photoaddition. Moreover, the two angular derivatives and the 4,4'-dimethyl-5-methoxypsoralen were unable to induce skin erythema, in striking contrast with the reference drugs, 8-MOP and 5-MOP; only the 3,4'-dimethyl-5-methoxypsoralen caused erythema, although to a substantially lower extent than that induced by the two parent compounds.

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