Biosynthesis and Studies of the Alkaline Sensitivity of the NO-Glucuronide of the Carcinogen N-2-Fluorenylacethydroxamic Acid<sup>*</sup>

Hill, Jim T.; Irving, Charles C.

doi:10.1021/bi00864a027

Cited by 22 publications

(4 citation statements)

References 7 publications

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“…Compound lib had an absorption maximum in methanol at 284 m/u (e 21,900; Figure 2, 2). The disappearance of the absorption maximum at 302 m/n which was present in Ha (Figure 2, 1) was also consistent with the removal of the Ar-acetyl group (Hill and Irving, 1967).…”

Section: Methodssupporting

confidence: 78%

“…Several years ago we reported the synthesis and characterization of Ila (Hill and Irving, 1967). This novel type of glucuronide (C-O-N linkage) was shown to be alkali labile.…”

Section: Discussionmentioning

confidence: 99%

“…Compound Ha was prepared biosynthetically by feeding rabbits A'-acetyl-Ar-2-fluorenyIhydroxylamine and isolating the glucuronide from urine (Hill and Irving, 1967); it was obtained as the crystalline sodium salt. The 9-14C compound was also prepared biosynthetically (Hill and Irving, 1967;Irving et al, 1969b).…”

Section: Methodsmentioning

confidence: 99%

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Synthesis of the O-glucuronide of N-2-fluorenylhydroxylamine. Reaction with nucleic acids and with guanosine 5'-monophosphate

Irving¹,

Russell²

1970

Biochemistry

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O-Glucuronides of arylhydroxylamines have not been previously reported in the literature. The facile removal of the AT-acetyl group from sodium (N-acetyl-A-2-fluorenylhydroxylamine /3-D-glucosid)uronate has led to the synthesis of sodium (AT-2-fluorenylhydroxylamine /3-D-glucosid)uronate. This latter glucuronide is unstable in aqueous solutions, decomposing completely within several minutes; the products of the decomposition have not yet been characterized. Sodium (Ar-2-fluoren-9-14C-ylhydroxylamine (J-D-glucosid)uronate has been synthesized and the compound reacts with RNA and DNA in vitro, resulting in the covalent binding of radioactivity to the nucleic acids. This glucuronide reacts with guanosine 5'-monophosphate to give 8-(tV-2-fluorenylamino)guanosine 5 '-monophosphate, but does not react with the 5'-monophosphates of uridine, cytidine, or adenosine. It is proposed that the O-glucuronide of 7V-2-fluorenylhydroxylamine might be formed as an intermediate metabolite of the carcinogen A'-acetyl-A'-2-fluorenylhydroxylamine, thus accounting, at least in part, for the observed binding of this carcinogen to rat liver DNA in vivo.

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Section: Methodssupporting

confidence: 78%

“…Several years ago we reported the synthesis and characterization of Ila (Hill and Irving, 1967). This novel type of glucuronide (C-O-N linkage) was shown to be alkali labile.…”

Section: Discussionmentioning

confidence: 99%

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Synthesis of the O-glucuronide of N-2-fluorenylhydroxylamine. Reaction with nucleic acids and with guanosine 5'-monophosphate

Irving¹,

Russell²

1970

Biochemistry

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“…Certain hydroxamic acids are eliminated in the rabbit as glucuronides, including N-acetyl-N-phenylhydroxamic acid (7) and N-acetyl-N-2-fluorenylhydroxamic acid (8). These differ from bufexamac by having two substituent groups on the nitrogen atom; moreover, their glucuronides are readily hydrolyzed by alkali.…”

Section: Discussionmentioning

confidence: 99%

Elimination of 4-n-Butoxyphenylacethydroxamic Acid (Bufexamac) in Man

Boreham

Cummings²,

Dell

et al. 1972

Journal of Pharmaceutical Sciences

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Bioactivation by Phase‐II‐Enzyme‐Catalyzed Conjugation of Xenobiotics

Grillo

2012

Encyclopedia of Drug Metabolism and Interactions

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Phase‐II‐enzyme‐catalyzed conjugation of xenobiotics with endogenous cofactors leads to hydrophilic derivatives that, in most cases, functions in the elimination and detoxification of xenobiotics from the body. However, this process can also mediate their bioactivation to chemically‐reactive and hence potentially toxic metabolites. The major conjugation reactions known to be involved in xenobiotic bioactivation are glucuronidation, sulfonation, acetylation, GSH conjugation, and acyl‐S‐CoA formation. Chemically‐reactive metabolites of xenobiotics can lead to covalent binding to protein and/or nucleic acids which some cases leads to intrinsic and/or idiosyncratic toxicity and carcinogenicity. This chapter will cover the known mechanisms of xenobiotic bioactivation by phase‐II‐drug‐conjugating enzymes.

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Biosynthesis and Studies of the Alkaline Sensitivity of the NO-Glucuronide of the Carcinogen N-2-Fluorenylacethydroxamic Acid^*

Abstract: Because of its occurrence as a major metabolite of the carcinogen N-2-fluorenylacetamide in susceptible species, the NO-glucuronide of N-2-fluorenylacethydroxamic acid was needed for studies of its

Cited by 22 publications

References 7 publications

Synthesis of the O-glucuronide of N-2-fluorenylhydroxylamine. Reaction with nucleic acids and with guanosine 5'-monophosphate

Synthesis of the O-glucuronide of N-2-fluorenylhydroxylamine. Reaction with nucleic acids and with guanosine 5'-monophosphate

Elimination of 4-n-Butoxyphenylacethydroxamic Acid (Bufexamac) in Man

Bioactivation by Phase‐II‐Enzyme‐Catalyzed Conjugation of Xenobiotics

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Biosynthesis and Studies of the Alkaline Sensitivity of the NO-Glucuronide of the Carcinogen N-2-Fluorenylacethydroxamic Acid*

Abstract: Because of its occurrence as a major metabolite of the carcinogen N-2-fluorenylacetamide in susceptible species, the NO-glucuronide of N-2-fluorenylacethydroxamic acid was needed for studies of its

Cited by 22 publications

References 7 publications

Synthesis of the O-glucuronide of N-2-fluorenylhydroxylamine. Reaction with nucleic acids and with guanosine 5'-monophosphate

Synthesis of the O-glucuronide of N-2-fluorenylhydroxylamine. Reaction with nucleic acids and with guanosine 5'-monophosphate

Elimination of 4-n-Butoxyphenylacethydroxamic Acid (Bufexamac) in Man

Bioactivation by Phase‐II‐Enzyme‐Catalyzed Conjugation of Xenobiotics

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Biosynthesis and Studies of the Alkaline Sensitivity of the NO-Glucuronide of the Carcinogen N-2-Fluorenylacethydroxamic Acid^*