Syntheses of hydroxyamino, nitroso and nitro derivatives of Trp-P-2 and Glu-P-1, amino acid pyrolysate mutagens, and their direct mutagenicities towards Salmonella typhimurium TA98 and TA98NR

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Abstract
Hydroxyamino, nitroso and nitro derivatives of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and 2-amino-6-methyldipyrido[1,2-a:3′,2′-d]imidazole (Glu-P-1), mutagens-carcinogens produced on pyrolysis of amino acids, were synthesized from Trp-P-2 and Glu-P-1. 3-Hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (N-OH-Trp-P-2) and 2-hydroxyamino-6-methyldipyrido[l,2-a:3′ ,2′-d]imidazole (N-OH-Glu-P-1) were obtained with good yields by controlled catalytic reduction of 3-nitro-l-methyl-5H-pyrido[4,3-b]indole and 2-nitro-6-methyldipyrido[1,2-a:3′,2′-d]imidazole. Subsequent oxidation of N-OH-Trp-P-2 and N-OH-Glu-P-1 with γ-manganese dioxide yielded 3-nitroso-1-methyl-5H-pyrido[4,3-b]indole and 2-nitroso-6-methyldipyrido[1,2-a:3′,2′-d]imidazole. All six synthesized compounds were mutagenic to Salmonella typhimurium TA98 without mammalian activation systems. The mutagenic activities of hydroxyamino and nitroso derivatives were identical for both S. typhimurium TA98 and TA98NR, the nitroreductase deficient strain. However, nitro derivatives were essentially mutagenic only towards S. typhimurium TA98.