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Biomedical subjects

C D Hufford

Publications and source records attributed to C D Hufford.

At least 55 records · Page 3Linked to original sources
PubMed1983

Demethylation of imipramine by enteric bacteria.

The ability of a number of aerobic and anaerobic bacteria to N-demethylate imipramine (I) to desipramine (II) has been investigated. Of the bacteria investigated, almost half were known inhabitants of the human GI tract. More than half of the enteric bacteria studied were capable of N-demethylating imipramine (I) to desipramine (II) to some extent in at least one medium. It was found that the medium in which the organism was grown had a significant effect on the N-demethylase activity observed.

Bacteria, Aerobic↗
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

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↗
PubMed1980

Antibacterial and antifungal activity of liriodenine and related oxoaporphine alkaloids.

Liriodenine was evaluated for its antibacterial and antifungal activity against several microorganisms. Other related oxoaporphine alkaloids also were evaluated. Attempts to prepare oxoaporphine alkaloids from N-acetylnoraporphines were unsuccessful, but an unexpected phenanthrene alkaloid was obtained. A novel N-demethylation reaction was noted when oxogaucine methiodide and liriodenine methiodide were treated with alumina.

Alkaloids↗
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↗
PubMed1975

Two antimicrobial alkaloids from heartwood of Liriodendron tulipifera L.

Alcoholic extracts of the heartwood of Liriodendron tulipifera have demonstrated antimicrobial activity against Staphylococcus aureus, Mycobacterium smegmatis, Candida albicans, and Aspergillus niger. The antimicrobial activity was associated only with the alkaloidal fraction. Separation of the active alkaloidal fraction by chromatography led to the isolation and identification of dehydroglaucine and liriodenine as the active components. Several other alkaloidal derivatives were prepared and tested. In addition to the active alkaloids, michelabine was also identified in the tertiary nonphenolic base fraction along with the lignan, lirioresinol-B-dimethyl ether, and two N-acetylnoraporphine alkaloids from the nonbasic fraction.

Alkaloids↗
PubMedDate not supplied

The use of microorganisms for the study of drug metabolism.

The potential for the use of microorganisms as tools in the study of drug metabolism appears to be unlimited. The selected examples cited here are only the beginning of what could develop into a widely accepted alternative in vitro model system for studying drug metabolism in humans. As with any other in vitro model system, it is not expected that microbial systems could ever replace animals in biomedical research. The acquisition of data regarding absorption, distribution, and excretion will still require whole animal systems. However, it is clear from the examples cited that microbial systems offer a reliable, reproducible alternative to small animal models for preliminary drug metabolism studies. Due to significant species variation, small animal models may, in many cases, be less reliable than microorganisms as predictive models of human metabolism. It has been estimated that approximately 70 million animals are used each year in the U.S. for biomedical research. The development of any techniques which curtail the sacrifice of such large numbers of animals is welcomed both by animal welfare groups who wish to ensure the humane treatment of laboratory animals and by researchers who additionally appreciate the more practical and economical benefits of such alternatives.

Animals↗