Synthesis, analysis and mutagenic activity of N-nitroso derivatives of glycosylamines and Amadori compounds: nitrosated model substances for the early Maillard reaction products.

A series of nine glycosylamines and an Amadori compound and their N-nitroso derivatives were synthesized. The structures were ascertained by spectroscopy and elemental analysis. The N-nitroso compounds were further characterized by denitrosation with hydrogen bromide-acetic acid, followed by detection of the liberated NO by a chemiluminescence detector. N-Nitroso derivatives of N-p-nitrophenyl/p-methylphenyl/p-carboxyphenyl pentosylamines, N-p-methylphenyl-1-deoxy-D-fructosylamine (Amadori compound) and N-3-ethylindole-D-xylosylamine were shown to be directly-acting mutagens in Salmonella typhimurium TA100. The activity of some of the compounds was similar to that of N-ethyl-N-nitrosourea. Their mutagenic activity was shown to be dependent on the structure of the amine and the sugar moieties and requires the presence of free hydroxyl groups in the sugar. The mutagenicity of N-nitrosoglycosylamines was attributed to their hydrolysis to arene diazonium cations. Their formation was detected via azo-coupling with N-ethyl-1-naphthylamine, using spectrophotometric and mass-spectrometric analyses. Our data implicate arene (alkyl) diazonium cations as the ultimate mutagens of N-nitrosoglycosylamines and N-nitroso Amadori compounds, a little explored class of N-nitroso compounds which may be formed in vivo.