Metabolic Transformation and Mechanism of Action of Mononitroso Caffeidine- A New Interpretation

G.   S.   Panda; R.   K.   Bhattacharya; S.   K.   Choudhuri

doi:10.2174/187153006776056602

Abstract

Although caffeine is not carcinogenic, its hydrolysed product, caffeidine causes human cancer, possibly through endogenous nitrosation to form mononitroso caffeidine (MNC). MNC undergoes enzymatic demethylation and reacts with cellular nucleophiles, notably DNA, via the formation of a putative imidazole diazonium ion. Its interaction with proteins has not been reported. The present work is based on the hypothesis that some active metabolites of MNC covalently interact with cellular DNA and/or proteins to initiate carcinogenesis. We report here the synthesis of a possible reactive metabolite of MNC, viz., N, 1-methyl-4(N-methyl-N-nitrosamino)-imidazole-5-carboxylic acid (MNIC). Its structure has been determined by uv, ir, nmr and mass spectral analyses and its interaction with egg albumin and human serum protein has been examined by uv and CD spectroscopy. We concluded that metabolic activation of MNC occurs through the formation of MNIC. Avoiding consumption of salted tea or coffee that prevents the intake of caffeidine will possibly eliminate the risk of MNC carcinogenicity.

Keywords: N, 1-methyl-4(N-methyl-N-nitrosamino)-imidazole-5-carboxylic acid (MNIC), asymmetric nitrosamine, demethylation, caffeine