Synthesis of methyl-substituted xanthotoxol to clarify prooxidant effect of methyl on radical-induced oxidation of DNA

4-Methyl-8-hydroxylpsoralen (MXan) and 4,9-dimethy1-8-hydroxylpsoralen (DMXan) were synthesized in order to clarify the effect of methyl on the antioxidant effectiveness of xanthotoxol (8-hydroxyl-psoralen, Xan), which were assessed by bleaching beta-carotene in linoleic acid-Triton emulsion, by interacting with 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS(+))center dot, 2,2'-dipheny1-1-picrylhydrazyl radical (DPPH), and galvinoxyl radical, and by protecting DNA against the oxidation induced by Cu(2+)/glutathione (GSH) and 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH). Methyl attaching to xanthotoxol did not affect its ability to protect linoleic acid against autoxidation and to inhibit Cu(2+)/GSH-induced oxidation DNA, but decreased its ability to scavenge ABTS(+)center dot and DPPH, and to protect DNA against AAPH-induced oxidation. Therefore, methyl attenuated the antioxidant effectiveness of xanthotoxol in radical-induced oxidation of DNA.