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 aminogu anidine (amidinohydrazone) is reported for 2-amino-5-chlorobenzophenon e amidinohydrazone 1 (G 256) as substrate. 2. The N-hydroxylated metab olite 2 (2-amino-5-chlorobenzophenone N-hydroxy-amidinohydrazone NOH-G 256) and a further metabolite of 1, the phenol 3, were identified by t ie and ms analysis. 3. The microsomal reduction of an N-hydroxyaminogu anidine (N-hydroxy-amidinohydrazone) was also demonstrated for the tra nsformation of 2 to 1. 4. Both the N-hydroxylation of the aminoguanidi ne and the retroreduction of the N-hydroxyaminoguanidine were characte rized by quantitative hplc analysis. 5. The conversion of the aminogua nidine 1 to N-hydroxyaminoguanidine 2 may be considered as an analogue of the physiological N-hydroxylation of arginine to N-hydroxy-arginin e by NO synthases.