Structural elucidation of a mutagenic metabolite of 3-amino-1-methyl-5H-pyrido[4,3-b]indole
Yamazoe, Y.; Ishii, K.; Kamataki, T.; Kato, R.
Drug Metabolism and Disposition the Biological Fate of Chemicals 9(3): 292-296
1981
ISSN/ISBN: 0090-9556 PMID: 6113943 Document Number: 172875
Metabolic activation of a tryptophan pyrolysate, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) by liver microsomes was studied. Trp-P-2 was converted to at least four metabolites (M-1 to M-4), which were separable by HPLC or TLC. Among them, the major metabolite (M-3) was extremely mutagenic to Salmonella typhimurium TA 98 in the absence of activating enzymes and the activity accounted for almost all mutagenic effects of Trp-P-2. Metabolite M-3 was identified as 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole by mass spectrometry and by conversion to the 4-chloro derivative of Trp-P-2 by treatment with hydrochloric acid. The latter compound was identified by NMR and mass spectrometry.