Reduction and glutathione conjugation reactions of N-acetyl-p-benzoquinone imine and two dimethylated analogues
N-Acetyl-3,5-dimethyl-p-benzoquinone imine, N-acetyl-2,6-dimethyl-p-benzoquinone imine, and N-acetyl-p-benzoquinone imine were synthesized via the oxidation of 3,5-dimethylacetaminophen, 2,6-dimethylacetaminophen, and acetaminophen, respectively. All three quinone imines were rapidly reduced to thei...
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| Veröffentlicht in: | Molecular pharmacology 1984-01, Vol.25 (1), p.151-157 |
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| container_title | Molecular pharmacology |
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| creator | ROSEN, G. M RAUCKMAN, E. J ELLINGTON, S. P DAHLIN, D. C CHRISTIE, J. L NELSON, S. D |
| description | N-Acetyl-3,5-dimethyl-p-benzoquinone imine, N-acetyl-2,6-dimethyl-p-benzoquinone imine, and N-acetyl-p-benzoquinone imine
were synthesized via the oxidation of 3,5-dimethylacetaminophen, 2,6-dimethylacetaminophen, and acetaminophen, respectively.
All three quinone imines were rapidly reduced to their corresponding semiquinone imines by NADPH-cytochrome P-450 reductase.
All three benzoquinone imines underwent comproportionation with their respective phenols to yield the corresponding semiquinone
imines, which in the presence of oxygen gave superoxide. Identification of this latter free radical was based on spin-trapping
techniques. Reduced GSH was found to be an excellent nucleophile toward N-acetyl-2,6-dimethyl-p-benzoquinone imine, whereas
this thiol behaved as a one-electron reductant toward N-acetyl-3,5-dimethyl-p-benzoquinone imine. Finally, GSH was determined
to act as both a nucleophile and a reductant toward N-acetyl-p-benzoquinone imine. |
| format | Article |
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were synthesized via the oxidation of 3,5-dimethylacetaminophen, 2,6-dimethylacetaminophen, and acetaminophen, respectively.
All three quinone imines were rapidly reduced to their corresponding semiquinone imines by NADPH-cytochrome P-450 reductase.
All three benzoquinone imines underwent comproportionation with their respective phenols to yield the corresponding semiquinone
imines, which in the presence of oxygen gave superoxide. Identification of this latter free radical was based on spin-trapping
techniques. Reduced GSH was found to be an excellent nucleophile toward N-acetyl-2,6-dimethyl-p-benzoquinone imine, whereas
this thiol behaved as a one-electron reductant toward N-acetyl-3,5-dimethyl-p-benzoquinone imine. Finally, GSH was determined
to act as both a nucleophile and a reductant toward N-acetyl-p-benzoquinone imine.</description><identifier>ISSN: 0026-895X</identifier><identifier>EISSN: 1521-0111</identifier><identifier>PMID: 6323948</identifier><identifier>CODEN: MOPMA3</identifier><language>eng</language><publisher>Bethesda, MD: American Society for Pharmacology and Experimental Therapeutics</publisher><subject>Animals ; Benzoquinones ; Biological and medical sciences ; Electron Spin Resonance Spectroscopy ; General and cellular metabolism. Vitamins ; Glutathione - metabolism ; Imines - chemical synthesis ; Imines - metabolism ; Medical sciences ; Microsomes, Liver - enzymology ; NADPH-Ferrihemoprotein Reductase - metabolism ; Oxidation-Reduction ; Pharmacology. Drug treatments ; Rats ; Structure-Activity Relationship</subject><ispartof>Molecular pharmacology, 1984-01, Vol.25 (1), p.151-157</ispartof><rights>1984 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,4010</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=9730929$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/6323948$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ROSEN, G. M</creatorcontrib><creatorcontrib>RAUCKMAN, E. J</creatorcontrib><creatorcontrib>ELLINGTON, S. P</creatorcontrib><creatorcontrib>DAHLIN, D. C</creatorcontrib><creatorcontrib>CHRISTIE, J. L</creatorcontrib><creatorcontrib>NELSON, S. D</creatorcontrib><title>Reduction and glutathione conjugation reactions of N-acetyl-p-benzoquinone imine and two dimethylated analogues</title><title>Molecular pharmacology</title><addtitle>Mol Pharmacol</addtitle><description>N-Acetyl-3,5-dimethyl-p-benzoquinone imine, N-acetyl-2,6-dimethyl-p-benzoquinone imine, and N-acetyl-p-benzoquinone imine
were synthesized via the oxidation of 3,5-dimethylacetaminophen, 2,6-dimethylacetaminophen, and acetaminophen, respectively.
All three quinone imines were rapidly reduced to their corresponding semiquinone imines by NADPH-cytochrome P-450 reductase.
All three benzoquinone imines underwent comproportionation with their respective phenols to yield the corresponding semiquinone
imines, which in the presence of oxygen gave superoxide. Identification of this latter free radical was based on spin-trapping
techniques. Reduced GSH was found to be an excellent nucleophile toward N-acetyl-2,6-dimethyl-p-benzoquinone imine, whereas
this thiol behaved as a one-electron reductant toward N-acetyl-3,5-dimethyl-p-benzoquinone imine. Finally, GSH was determined
to act as both a nucleophile and a reductant toward N-acetyl-p-benzoquinone imine.</description><subject>Animals</subject><subject>Benzoquinones</subject><subject>Biological and medical sciences</subject><subject>Electron Spin Resonance Spectroscopy</subject><subject>General and cellular metabolism. Vitamins</subject><subject>Glutathione - metabolism</subject><subject>Imines - chemical synthesis</subject><subject>Imines - metabolism</subject><subject>Medical sciences</subject><subject>Microsomes, Liver - enzymology</subject><subject>NADPH-Ferrihemoprotein Reductase - metabolism</subject><subject>Oxidation-Reduction</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Structure-Activity Relationship</subject><issn>0026-895X</issn><issn>1521-0111</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1984</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kE1LxDAQhoso67r6E4Qe1FshaZpucpTFL1gURMFbmSbTNkvb1CZlqb_eulu8zDDzPvMyMyfBkvKYRoRSehosCYnTSEj-dR5cOLcjhCZckEWwSFnMZCKWgX1HPShvbBtCq8OyHjz4aioxVLbdDSUctB7hALnQFuFrBAr9WEddlGP7Y78H0_4NmMZM8c_G722oTYO-GmvwqKcm1LYc0F0GZwXUDq_mvAo-Hx8-Ns_R9u3pZXO_jSoqiI-SlLOEp6JgOtUkVlxIyiXqdZHGupBSMoFKaCUIyZEITZlUuchTgDjXCRNsFdwdfbt-2g-dzxrjFNY1tGgHlwlKyJonbAKvZ3DIG9RZ15sG-jGbPzTpN7MOTkFd9NAq4_4xuWZExnLCbo9YZcpqb3rMugr6BpSd7h6zmGc0o5yyX-mqfwQ</recordid><startdate>19840101</startdate><enddate>19840101</enddate><creator>ROSEN, G. M</creator><creator>RAUCKMAN, E. J</creator><creator>ELLINGTON, S. P</creator><creator>DAHLIN, D. C</creator><creator>CHRISTIE, J. L</creator><creator>NELSON, S. D</creator><general>American Society for Pharmacology and Experimental Therapeutics</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>19840101</creationdate><title>Reduction and glutathione conjugation reactions of N-acetyl-p-benzoquinone imine and two dimethylated analogues</title><author>ROSEN, G. M ; RAUCKMAN, E. J ; ELLINGTON, S. P ; DAHLIN, D. C ; CHRISTIE, J. L ; NELSON, S. D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h180t-46534568f3d6d02c589159ed7f62df99938ec8dc800be08d139cb8b6aa2bd4383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1984</creationdate><topic>Animals</topic><topic>Benzoquinones</topic><topic>Biological and medical sciences</topic><topic>Electron Spin Resonance Spectroscopy</topic><topic>General and cellular metabolism. Vitamins</topic><topic>Glutathione - metabolism</topic><topic>Imines - chemical synthesis</topic><topic>Imines - metabolism</topic><topic>Medical sciences</topic><topic>Microsomes, Liver - enzymology</topic><topic>NADPH-Ferrihemoprotein Reductase - metabolism</topic><topic>Oxidation-Reduction</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ROSEN, G. M</creatorcontrib><creatorcontrib>RAUCKMAN, E. J</creatorcontrib><creatorcontrib>ELLINGTON, S. P</creatorcontrib><creatorcontrib>DAHLIN, D. C</creatorcontrib><creatorcontrib>CHRISTIE, J. L</creatorcontrib><creatorcontrib>NELSON, S. D</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ROSEN, G. M</au><au>RAUCKMAN, E. J</au><au>ELLINGTON, S. P</au><au>DAHLIN, D. C</au><au>CHRISTIE, J. L</au><au>NELSON, S. D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reduction and glutathione conjugation reactions of N-acetyl-p-benzoquinone imine and two dimethylated analogues</atitle><jtitle>Molecular pharmacology</jtitle><addtitle>Mol Pharmacol</addtitle><date>1984-01-01</date><risdate>1984</risdate><volume>25</volume><issue>1</issue><spage>151</spage><epage>157</epage><pages>151-157</pages><issn>0026-895X</issn><eissn>1521-0111</eissn><coden>MOPMA3</coden><abstract>N-Acetyl-3,5-dimethyl-p-benzoquinone imine, N-acetyl-2,6-dimethyl-p-benzoquinone imine, and N-acetyl-p-benzoquinone imine
were synthesized via the oxidation of 3,5-dimethylacetaminophen, 2,6-dimethylacetaminophen, and acetaminophen, respectively.
All three quinone imines were rapidly reduced to their corresponding semiquinone imines by NADPH-cytochrome P-450 reductase.
All three benzoquinone imines underwent comproportionation with their respective phenols to yield the corresponding semiquinone
imines, which in the presence of oxygen gave superoxide. Identification of this latter free radical was based on spin-trapping
techniques. Reduced GSH was found to be an excellent nucleophile toward N-acetyl-2,6-dimethyl-p-benzoquinone imine, whereas
this thiol behaved as a one-electron reductant toward N-acetyl-3,5-dimethyl-p-benzoquinone imine. Finally, GSH was determined
to act as both a nucleophile and a reductant toward N-acetyl-p-benzoquinone imine.</abstract><cop>Bethesda, MD</cop><pub>American Society for Pharmacology and Experimental Therapeutics</pub><pmid>6323948</pmid><tpages>7</tpages></addata></record> |
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| ispartof | Molecular pharmacology, 1984-01, Vol.25 (1), p.151-157 |
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| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Benzoquinones Biological and medical sciences Electron Spin Resonance Spectroscopy General and cellular metabolism. Vitamins Glutathione - metabolism Imines - chemical synthesis Imines - metabolism Medical sciences Microsomes, Liver - enzymology NADPH-Ferrihemoprotein Reductase - metabolism Oxidation-Reduction Pharmacology. Drug treatments Rats Structure-Activity Relationship |
| title | Reduction and glutathione conjugation reactions of N-acetyl-p-benzoquinone imine and two dimethylated analogues |
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