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

Abstract

4-methyl-8-hydroxylpsoralen (MXan) and 4,9-dimethyl-8-hydroxylpsoralen (DMXan) were synthesized in order to clarify the effect of methyl on the antioxidant effectiveness of xanthotoxol (8-hydroxylpsoralen, 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+), 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH), and galvinoxyl radical, and by protecting DNA against the oxidation induced by Cu2+/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 Cu2+/GSH-induced oxidation DNA, but decreased its ability to scavenge ABTS+ and DPPH, and to protect DNA against AAPH-induced oxidation. Therefore, methyl attenuated the antioxidant effectiveness of xanthotoxol in radical-induced oxidation of DNA.