CYTOCHROME P450-DEPENDENT N-HYDROXYLATION OF AN AMINOGUANIDINE (AMIDINOHYDRAZONE) AND MICROSOMAL RETROREDUCTION OF THE N-HYDROXYLATED PRODUCT

被引：22

作者：

CLEMENT, B ^{[1
]}

SCHULTZEMOSGAU, MH ^{[1
]}

RICHTER, PH ^{[1
]}

BESCH, A ^{[1
]}

机构：

[1] UNIV GREIFSWALD,DEPT PHARM,D-17489 GREIFSWALD,GERMANY

来源：

XENOBIOTICA | 1994年 / 24卷 / 07期

关键词：

D O I：

10.3109/00498259409043269

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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-hydroxy-amidinohydrazone NOH-G256) and a further metabolite of 1, the phenol 3, were identified by tie and ms analysis. 3. The microsomal reduction of an N-hydroxyaminoguanidine (N-hydroxy-amidinohydrazone) 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.

引用

页码：671 / 688

页数：18

共 43 条

[1]

BORCHERT HH, 1993, PHARMAZIE, V48, P365

[2]

CLEMENT B, 1993, MOL PHARMACOL, V43, P335

[3] CYTOCHROME-P450 DEPENDENT N-HYDROXYLATION OF A GUANIDINE (DEBRISOQUINE), MICROSOMAL CATALYZED REDUCTION AND FURTHER OXIDATION OF THE N-HYDROXY-GUANIDINE METABOLITE TO THE UREA DERIVATIVE - SIMILARITY WITH THE OXIDATION OF ARGININE TO CITRULLINE AND NITRIC-OXIDE [J].