Potential Metabolic Mutagens of Caffeine and Various Methylxanthines

Xanthine N-carbinols, potential metabolites of caffeine and other methylxanthines, have been synthesized, characterized, and derivatized. Such intermediates, the initial metabolites arising from the cytochrome P-450 oxidation of the nitrogen-bound methyl groups, may be viewed as biological N-carbino...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 1988-11, Vol.77 (11), p.955-958
Main Authors: Lander, Naphtali, Soloway, Albert H., Minton, John P., Rawal, Bhupat D., Gairola, Chandra C.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Caffeine - analogs & derivatives
Caffeine - analysis
Caffeine - toxicity
Chemical mutagenesis
Drug toxicity and drugs side effects treatment
In Vitro Techniques
Liver - metabolism
Magnetic Resonance Spectroscopy
Medical sciences
Miscellaneous (drug allergy, mutagens, teratogens...)
Mutagenicity Tests
Mutagens
Pharmacology. Drug treatments
Rats
Toxicology
Xanthines - analysis
Xanthines - chemical synthesis
Xanthines - toxicity
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Summary:Xanthine N-carbinols, potential metabolites of caffeine and other methylxanthines, have been synthesized, characterized, and derivatized. Such intermediates, the initial metabolites arising from the cytochrome P-450 oxidation of the nitrogen-bound methyl groups, may be viewed as biological N-carbinols capable of alkylating proteins and nucleic acids. Evaluation of these compounds against Salmonella typhimurium, strain TA100, has demonstrated that, in contrast to caffeine, 7-hydroxymethyltheophylline and the 3,7-bis(hydroxymethyl)-1-methylxanthine mixture did exhibit cytotoxicity. There was no evidence of mutagenesis and it is possible that the Ames assay system is not applicable to N-carbinols.
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.2600771112