Structural elucidation of a mutagenic metabolite of 3-amino-1-methyl-5H-pyrido[4,3-b]indole.
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.
D000818:Animals; D001711:Biotransformation; D002243:Carbolines / Q000378:metabolism*; D066298:In Vitro Techniques; D007211:Indoles / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009153:Mutagens / Q000378:metabolism*; D051381:Rats
D002243:Carbolines; D007211:Indoles; D009153:Mutagens; C027210:3-hydroxyamino-1-methyl-5H-pyrido(4,3-b)indole; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole