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-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.
Lander
N
N
College of Pharmacy, Ohio State University, Columbus 43210.
Soloway
A H
AH
Minton
J P
JP
Rawal
B D
BD
Gairola
C C
CC
D000818:Animals; D002110:Caffeine / Q000031:analogs & derivatives* / Q000032:analysis / Q000633:toxicity*; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D009152:Mutagenicity Tests; D009153:Mutagens; D051381:Rats; D014970:Xanthines / Q000032:analysis / Q000138:chemical synthesis / Q000633:toxicity*
D009153:Mutagens; D014970:Xanthines; D002110:Caffeine