Cytochrome P450-dependent N-hydroxylation of an aminoguanidine (amidinohydrazone) and microsomal retroreduction of the N-hydroxylated product

1. The first example of a P450-dependent N-hydroxylation of an aminoguanidine (amidinohydrazone) is reported for 2-amino-5-chlorobenzophenone amidinohydrazone 1 (G256) as substrate.2. The N-hydroxylated metabolite 2 (2-amino-5-chlorobenzophenone N-hydroxy-amidinohydrazone NOH-G256) and a further metabolite of 1, the phenol 3, were identified by tlc and ms analysis.3. The microsomal reduction of an N-hydroxyaminoguanidine (N-hydroxy-amidino-hydrazone) was also demonstrated for the transformation of 2 to 1.4. Both the N-hydroxylation of the aminoguanidine and the retroreduction of the N-hydroxyaminoguanidine were characterized by quantitative hplc analysis.5. The conversion of the aminoguanidine 1 to N-hydroxyaminoguanidine 2 may be considered as an analogue of the physiological N-hydroxylation of arginine to N-hydroxy-arginine by NO synthases.