Hydroxyl radical mediated demethylenation of (methylenedioxy)phenyl compounds.
The oxidative demethylenation reactions of (methylendioxy)phenyl compounds (MDPs), (methylenedioxy)benzene (MDB), (methylenedioxy)amphetamine (MDA), and (methylenedioxy)methamphetamine (MDMA), were evaluated by using two hydroxyl radical generating systems, the autoxidation of ascorbate in the presence of iron-EDTA and the iron-catalyzed Haber-Weiss reaction conducted by xanthine/xanthine oxidase with iron-EDTA. Reaction products generated when MDB, MDA, and MDMA were incubated with the ascorbate or xanthine oxidase system were catechol, dihydroxyamphetamine (DHA), and dihydroxymethamphetamine (DHMA), respectively. The reaction required the presence of either ascorbic acid or xanthine oxidase. Levels of each catechol increased in proportion to ferric ion concentration and were suppressed by desferrioxamine B methanesulfonate (desferal). Catalase (CAT) inhibited the oxidation by the ascorbate system whereas superoxide dismutase (SOD) had little effect. The addition of hydrogen peroxide to the reaction mixture stimulated the oxidation, but the reaction was not initiated by hydrogen peroxide alone, suggesting that hydrogen peroxide acts as a precursor of hydroxyl radical. SOD and CAT suppressed the demethylenation reactions in the xanthine oxidase system. Hydroxyl radical scavenging agents such as ethanol, benzoate, DMSO, and thiourea effectively inhibited the oxidation by both systems. Urea, which has little effect on hydroxyl radical, was without any effect. These results indicated that hydroxyl radical can effect the cleavage of methylenedioxy group on MDPs.
Kumagai
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Department of Pharmacology, UCLA School of Medicine 90024-1735.
Lin
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Schmitz
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Cho
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D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000737:chemistry*; D001205:Ascorbic Acid / Q000737:chemistry; D004149:Dioxoles / Q000737:chemistry*; D004492:Edetic Acid / Q000737:chemistry; D004563:Electrochemistry; D006861:Hydrogen Peroxide / Q000737:chemistry; D006878:Hydroxides / Q000737:chemistry*; D017665:Hydroxyl Radical; D007501:Iron / Q000737:chemistry; D008745:Methylation; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D010084:Oxidation-Reduction; D013481:Superoxides / Q000378:metabolism
D004149:Dioxoles; D006878:Hydroxides; D013481:Superoxides; D017665:Hydroxyl Radical; D015104:3,4-Methylenedioxyamphetamine; D004492:Edetic Acid; D006861:Hydrogen Peroxide; D007501:Iron; C040539:1,3-benzodioxole; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D001205:Ascorbic Acid