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

Xenobiotica. 1994 Jul;24(7):671-88. doi: 10.3109/00498259409043269.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzophenones / metabolism
  • Benzophenones / pharmacokinetics*
  • Biotransformation
  • Cytochrome P-450 Enzyme System / metabolism*
  • Hydrazones / metabolism
  • Hydrazones / pharmacokinetics*
  • Hydroxylation
  • Mass Spectrometry
  • Microsomes, Liver / enzymology*
  • Oxidation-Reduction
  • Rabbits
  • Rats
  • Spectrophotometry, Ultraviolet

Substances

  • 2-amino-5-chlorobenzophenone N-hydroxyamidinohydrazone
  • Benzophenones
  • Hydrazones
  • 2-amino-5-chlorobenzophenoneamidinohydrazone
  • Cytochrome P-450 Enzyme System