Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

3-Methyl-1-phenyltriazene and a series of ring-substituted derivatives (4-methylphenyl, 4-chlorophenyl, and 2,4,6-trichlorophenyl), structurally related benzenediazonium fluoborates and phenyl azides, as well as the recently isolated [1-methyl-3-(2,4,6-trichlorophenyl)-2-triazeno]methyl-beta-D-glucopyranoside uronic acid, were studied for their mutagenic activity in Salmonella typhimurium strains. Of these compounds, the 3-methyl-1-phenyltriazene derivatives and 2,4,6-trichlorobenzenediazonium fluoborate were found to be direct-acting mutagens; the glucuronide was active in strain TA 1530 only after deconjugation with beta-glucuronidase. The half-lives of the monomethylphenyltriazenes in vitro were determined and compared with their methylating activity towards 4-(4-nitrobenzyl)pyridine and their mutagenicity. The results are discussed in relation to the possible mechanism of action of the N,N-dimethylphenyltriazenes and their monomethyl derivatives as mutagens and organ-specific carcinogens.
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PMID:Mutagenic and alkylating activities of 3-methyl-1-phenyltriazenes and their possible role as carcinogenic metabolites of the parent dimethyl compounds. 706 18

A non-redox dual inhibitor of both cyclooxygenase and 5-lipoxygenase, [2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5- yl]-[2'-14C]-acetic acid (3, ML 3000), was synthesized as [14C]-labelled compound and administered orally to rats. Distribution of radioactivity was examined by use of whole-body autoradiography after administration of doses in the range 13.7-26.6 mg/kg. Highest tissue levels were detected in the lung, liver, kidney, heart and large and small intestine. 48 h after administration, 58.3% of the total radioactivity was found in the feces and 7.9% in the urine. The distribution of radioactivity in the tissue, time course of plasma concentration, urinary and fecal excretion as well as hydrolysis experiments with beta-glucuronidase suggest an enterohepatic circulation and metabolization to glucuronides.
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PMID:Distribution and excretion of [14C]-labelled [2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5- yl]- [2'-14C]-acetic acid in rats. 774 83

An HPLC method was developed and validated for the determination in human plasma and urine of the enantiomers of eliprodil, (+/-)-alpha-(4-chlorophenyl)-4[(4-fluorophenyl) methyl]piperidine-1-ethanol hydrochloride, a new anti-ischaemic agent administered as a racemate. Both enantiomers are present in human plasma in unchanged and glucuroconjugated form, whereas only the glucuroconjugated form is excreted into urine; as a consequence, such metabolites in human plasma and urine should be submitted to enzymatic deconjugation with beta-glucuronidase (Escherichia coli) before being extracted. The general method involves a liquid-liquid extraction of eliprodil and internal standard from alkalinized plasma or urine with n-hexane, evaporation of the organic phase and derivatization with (S)-(+)-naphthylethyl isocyanate to give carbamate diastereoisomeric derivatives of (S)-(+)- and (R)-(-)-eliprodil and internal standard; after evaporation of the derivatizing mixture and dissolution of the residue in a small volume of phosphate buffer-acetonitrile (60:40, v/v), an aliquot is injected into a column-switching HPLC system. The derivatized sample extract is purified on a precolumn filled with C8-bonded silica material, which is flushed with acetonitrile-water, then diastereoisomers of eliprodil and the internal standard are automatically transferred by the mobile phase to the analytical column. The analytical column is a C8 type, specially deactivated for basic compounds, the mobile phase is 0.025 M phosphate buffer (pH 2.6)-methanol-acetonitrile (42:2:56) at a flow-rate of 1.2 ml min-1 and fluorimetric detector operating at lambda ex = 275 nm and lambda em = 336 nm is used. The retention times, under these conditions, are about 16 and 17 min for (S)-(+)- and (R)-(-)-eliprodil diastereoisomers, respectively, and about 19 min for the first-eluted diastereoisomer of the internal standard. During the analysis time, the precolumn, reset in a different path from that of the analytical column, is back-flushed with different solvents, then re-equilibrated with acetonitrile-water before the next injection. Linearity in plasma, for unchanged eliprodil enantiomers, was assessed in the range 0.15-10 ng ml-1 and for total eliprodil enantiomers (unchanged + conjugated) in the range 0.75-500 ng ml-1; the limit of quantitation (LOQ) is 0.15 ng ml-1 for each unchanged enantiomer and 0.75 ng ml-1 for each total enantiomer. Linearity was also assessed in urine for total (conjugated) eliprodil enantiomers in the range 50-25 000 ng ml-1; the LOQ is 50 ng ml-1 for each enantiomer. The intra- and inter-day precision and accuracy of the method were investigated in plasma and urine and found to be satisfactory for pharmacokinetic studies. The method has been extensively used in pharamcokinetic studies in man treated with a 20-mg dose of eliprodil racemate and some results of this application are reported.
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PMID:Stereoselective determination of unchanged and glucuroconjugated eliprodil, a new anti-ischaemic drug, in human plasma and urine by precolumn derivatization and column-switching high-performance liquid chromatography with fluorescence detection. 900 57