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 (G 256) as substrate. 2. The N-hydroxylated metabolite 2 (2-amino-5-chlorobenzophenone N-hydroxyamidinohydrazone 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-hydroxyarginine by NO synthases.
Clement
B
B
Pharmaceutical Institute, Christian-Albrechts-University Kiel, Germany.
Schultze-Mosgau
M H
MH
Richter
P H
PH
Besch
A
A
D000818:Animals; D001577:Benzophenones / Q000378:metabolism / Q000493:pharmacokinetics*; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006835:Hydrazones / Q000378:metabolism / Q000493:pharmacokinetics*; D006900:Hydroxylation; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000201:enzymology*; D010084:Oxidation-Reduction; D011817:Rabbits; D051381:Rats; D013056:Spectrophotometry, Ultraviolet
C090299:2-amino-5-chlorobenzophenone N-hydroxyamidinohydrazone; D001577:Benzophenones; D006835:Hydrazones; C079368:2-amino-5-chlorobenzophenoneamidinohydrazone; D003577:Cytochrome P-450 Enzyme System