The role of cytochrome P-450 in the biological nuclear N-oxidation of aminoaza-heterocyclic drugs and related compounds

Abstract

Aminoazaheterocycles are a group of organic molecules having an amino group attached to a carbon adjacent to a ring nitrogen in an aromatic system. The nucleic acid bases adenine, guanine, cytosine and the vitamin thiamine are examples of ortho-aminoazaheterocycles which exist naturally as essential compounds required for the proper physiological and biochemical function of biological systems. A large number of important medicinal agents covering a wide spectrum of pharmacological activities also belongs to this chemical group: e.g. the anti-anaemic, folic acid; the antimalarial, pyrimethamine; the broad spectrum antibacterials, trimethoprim and cefotaxime; the anticancer agent, metoprine; the diuretics, triamterene and amiloride (Fig. 10.1). Many aminoazaheterocycles are also in vivo metabolites of medicinal agents (Fig. 10.2). A number of known examples of aminoazaheterocycles, which are among the most mutagenic and carcinogenic compounds, are formed during the cooking process of foods and have been detected in charred meat, broiled fish and in pyrolysates of proteins and amino acids (Fig. 10.3), (Sugimura and Nagao, 1979; Sugimura and Sato, 1983).