Synthesis, purification and mutagenicity of 2-hydroxyamino-3-methylimidazolo[4,5-f]quinoline.
Synthesis of 2-hydroxyamino-3-methylimidazolo[4,5-f]quinoline (N-hydroxy-IQ), a reactive metabolite of 2-amino-3-methylimidazolo[4,5-f]quinoline (IQ), was achieved by a modification of an earlier method. N-Hydroxy-IQ was purified by a two-step procedure involving C18 Sep-Pack and semi-preparative h.p.l.c. Additional h.p.l.c. methods were developed to monitor the synthesis of N-hydroxy-IQ, and to measure IQ and other IQ derivatives on the same h.p.l.c. profile. The structure of N-hydroxy-IQ was confirmed by mass spectral analysis following derivatization to azoxy-IQ, phenyl-azoxy-IQ and acetoxy-acetamido-IQ, and by chemical reactivity studies. Mutagenicity studies with the nitro-reductase-deficient strain of Salmonella TA98 showed that N-hydroxy-IQ is directly mutagenic, having a specific activity of 2 X 10(4) revertants/nmol. The data confirm that N-hydroxy-IQ is a mutagenic metabolite of IQ and further implicate the hydroxylamine in the carcinogenicity of IQ.
D007093:Imidazoles / Q000138:chemical synthesis* / Q000633:toxicity; D009153:Mutagens / Q000138:chemical synthesis* / Q000302:isolation & purification; D011804:Quinolines / Q000378:metabolism*
D007093:Imidazoles; D009153:Mutagens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C032012:2-hydroxyamino-3-methylimidazolo(4,5-f)quinoline