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Biomedical subjects

A M Clark

Publications and source records attributed to A M Clark.

At least 145 records · Page 8Linked to original sources
PubMed1982

High-performance liquid chromatographic analysis of the metabolism of primaquine and the identification of a new mammalian metabolite.

Using rats that had been dosed with 20 mg/kg of primaquine diphosphate (11.4 mg/kg free base), it was found that the drug underwent a metabolic oxidative deamination to give 8-(3-carboxy-1-methylpropylamino)-6-methoxyquinoline. The presence of this new mammalian metabolite was verified using high-performance liquid chromatographic, gas chromatographic, and mass spectral methods. A quantitative high-performance liquid chromatographic method for the determination of primaquine and the carboxylic acid metabolite in plasma using only 50 microliters of whole blood from the rat was developed and the method could be used to detect levels as low as 0.05 microgram/ml of the metabolite. Following intravenous administration of the drug, it was found that the plasma levels of primaquine fell very rapidly and after 30 min, the levels of the metabolite were much higher than those of primaquine.

Animals↗
PubMed1982

Study of the metabolic conversion of imipramine and desipramine to N-nitrosodesipramine by bacteria using a nitrogen-selective GC analysis.

A GC method using dual nitrogen selective and flame ionization detectors was developed for the determination of N-nitrosodesipramine using N-butyryldesipramine as the internal standard. The precision of the method was found to be +/- 5.0% and the accuracy was +/- 4.9%. The method could be used to detect 10 ng/ml of N-nitrosodesipramine in bacterial cultures. When desipramine and sodium nitrite were incubated with aerobic or anaerobic bacteria, the nitrosamine level was found to be 10-300 times higher than the controls. When imipramine and potassium nitrate were incubated with a mixed anaerobic culture, the level of N-nitrosodesipramine was found to be 4.5 times higher than the control.

Aerobiosis↗
PubMed1981

Mechanism of hydroxylation of biphenyl by Cunninghamella echinulata.

The hydroxylation of [U-2H]biphenyl and [2,2',3,3',5,5',6,6'-2H]biphenyl by Cunninghamella echinulata A.T.C.C. 9244 has been studied. G.l.c.-mass-spectrometry analyses indicate the lack of an isotope effect during the hydroxylation of the perdeuterated substrate. Both g.l.c.-mass spectrometry and 1H n.m.r. were used to definitively demonstrate the presence of a 1,2-hydride-shift during the microbiological hydroxylation of [2,2',3,3',5,5',6,6'-2H]biphenyl.

Biphenyl Compounds↗
PubMed1981

Metabolism of imipramine by microorganisms.

The microbial metabolism of imipramine was studied using selected fungal organisms. The major microbial metabolites were isolated, and their structures were established by spectroscopic analyses (particularly 13C-NMR) and by comparison with authentic samples. The microbial metabolites identified included 2-hydroxyimipramine, 10-hydroxyimipramine, iminodibenzyl, imipramine-N-oxide, and desipramine; these metabolites also have been found in mammalian metabolism studies.

Biotransformation↗
PubMed1981

Metabolism of phencyclidine by microorganisms.

A number of microorganisms were screened for their ability to metabolize phencyclidine. Two microorganisms, Beauveria sulfurescens and Cunninghamella echinulata, produced hydroxylated metabolites, which were identified as 1-(1-phenylcyclohexyl)-4-hydroxypiperidine and 4-phenyl-4-piperidinocyclohexanol by high-pressure liquid chromatographic analysis.

Basidiomycota↗
PubMed1981

Antimicrobial activity of phenolic constituents of Magnolia grandiflora L.

Three phenolic constituents of Magnolia grandiflora L. were shown to possess significant antimicrobial activity using an agar well diffusion assay. Magnolol, honokiol, and 3.5'-diallyl-2'-hydroxy-4-methoxybiphenyl exhibited significant activity against Gram-positive and acid-fast bacteria and fungi. The minimum inhibitory concentrations were determined for each compound using a twofold serial dilution assay.

Anti-Bacterial Agents↗
PubMed1981

Primaquine: metabolism by microorganisms and 13C nuclear magnetic resonance assignments.

Primaquine (I), a 6-methoxy-8-aminoquinoline derivatives used for the treatment of malaria, has been subjected to metabolic studies using microorganisms. A total of 77 microorganisms (fungi and Streptomyces spp.) were evaluated for their ability to metabolize primaquine. Of these, 23 were found to convert primaquine to one or more metabolites (thin-layer chromatography analysis). Preparative scale fermentation of primaquine with four different microorganisms resulted in the isolation of two metabolites, identified as 8-(4-acetamido-1-methylbutylamino)-6-methoxyquinoline (II) and 8-(3-carboxyl-1-methylpropylamino)-6-methoxyquinoline (III). The structures of the metabolites were proposed based primarily on a comparison of the 13C nuclear magnetic resonance spectra of II and the methyl ester of III (IV) with that of primaquine. The structures of both metabolites II and III were confirmed by direct comparison with authentic samples.

Aspergillus flavus↗
PubMed1979

Microbial transformations and 13C-NMR analysis of colchicine.

Several microorganisms were screened for their ability to biotransform colchicine, and two were selected for preparative scale fermentations. Streptomyces spectabilis and Streptomyces griseus both produced O2-demethylcolchicine and O3-demethylcolchicine but in different amounts. The 13C-NMR assignments of colchicine, O10-demethylcolchicine, and trimethylcolchicinic acid are reported and were used to help identify the structures of the metabolites.

Bacteria↗
PubMed1979

N-demethylation of lergotrile by Streptomyces platensis.

Thirty-eight microorganisms were screened for their ability to produce metabolites of the semisynthetic alkaloid, lergotrile. A total of five microorganisms were found to biotransform lergotrile, and N-desmethyl lergotrile was detected as the principal metabolite with most organisms. Streptomyces platensis (NRRL 2364) appeared to form the metabolite in highest yield, and a preparative-scale conversion was accomplished with a recovered yield of 50%. Structure proof was accomplished with comparative thin-layer chromatography, mixed melting point, mass spectrometry, and remethylation to lergotrile.

Biotransformation↗
PubMed1978

Twins and Q-banded chromosome polymorphisms.

Q-banded chromosomal analyses were performed on 24 pairs of twins to determine the stability and heritability of chromosome polymorphisms, and to establish the use of these markers in the determination of twin zygosity. Sixteen twin pairs were determined monozygotic by chromosome polymorphism analysis and confirmed monozygotic by blood group genotyping. No two genetically distinct individuals had the same polymorphic pattern, suggesting the individuality of each morphological karyotype. The frequencies for the various types of chromosome polymorphisms, including stalk length variations, were determined. Analysis of frequency distribution for variant combinations showed random association.

Chromosome Banding↗