Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Editor

Personal info

View

About

Terms

Javascript disabled

Please enable Javascript support in your browser to use this application.

Instructions on how to enable JavaScript on different browsers can be found here: http://www.google.com/support/bin/answer.py?answer=23852.

[edit this page]

Chemical Compound Review:

BP-11260 N'- hydroxybenzenecarboximidamide

Synonyms: ZINC12375727, AKOS004905617, HMS1401K03, IDI1_007034, AC1NS5VO, ...

Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of N-Hydroxybenzamidine

Genotoxic activities of benzamidine and its N-hydroxylated metabolite benzamidoxime in Salmonella typhimurium and mammalian cells [1].

High impact information on N-Hydroxybenzamidine

In this study, a N-reductive enzyme system of pig liver mitochondria using benzamidoxime as a model substrate was identified [2].
Besides the known reduction of N-hydroxylated benzamidine (benzamidoxime) (2) to benzamidine (1), glucuronidation and, to a much smaller extent, sulfation of 2 to benzamidoxime O-glucuronide (3) and benzamidoxime O-sulfate (4) by cultured pig hepatocytes were found [3].
To reconstitute the complete activity of the benzamidoxime reductase, the system required cytochrome b(5), NADH-cytochrome b(5)-reductase, and the benzamidoxime reductase, a cytochrome P450 enzyme, which has been purified to homogeneity from pig liver [4].
Reduction of amphetamine hydroxylamine and other aliphatic hydroxylamines by benzamidoxime reductase and human liver microsomes [4].
One responsible enzyme system, the microsomal benzamidoxime reductase, consisting of cytochrome b5, its reductase, and a cytochrome P450 isoenzyme, was isolated from pig liver microsomes (J Biol Chem 272:19615-19620) [5].

Associations of N-Hydroxybenzamidine with other chemical compounds

Indirect evidence for the formation of a glucuronide of benzamidoxime has been obtained from in vitro experiments, but it could not be established that this process was a decisive factor in the genotoxicity of benzamidoxime [1].

Gene context of N-Hydroxybenzamidine

UGT1A9 is the most efficient enzyme conjugating benzamidoxime, whereas the conversion activities of UGT1A1 and UGT1A3 were 60-fold lower [6].
For the N-reduction of benzamidoxime an oxygen-insensitive liver microsomal enzyme system that required cytochrome b5, NADH-cytochrome b5 reductase and a cytochrome P450 isoenzyme of the subfamily 2D has been described [7].
Furthermore, the involvement of human UDP-glucuronosyltransferases (UGTs) was examined by incubating benzamidoxime in the presence of eight human hepatic recombinant UGT enzymes [6].

Analytical, diagnostic and therapeutic context of N-Hydroxybenzamidine

In the Salmonella typhimurium mutagenicity test (TA 98 and TA 100) benzamidoxime alone exhibited a low mutagenicity in the TA 98 strain in the presence of rabbit liver S-9 fractions [1].

References

Genotoxic activities of benzamidine and its N-hydroxylated metabolite benzamidoxime in Salmonella typhimurium and mammalian cells. Clement, B., Schmezer, P., Weber, H., Schlehofer, J.R., Schmitt, S., Pool, B.L. J. Cancer Res. Clin. Oncol. (1988) [Pubmed]
Identification of the Missing Component in the Mitochondrial Benzamidoxime Prodrug-converting System as a Novel Molybdenum Enzyme. Havemeyer, A., Bittner, F., Wollers, S., Mendel, R., Kunze, T., Clement, B. J. Biol. Chem. (2006) [Pubmed]
Phase 2 metabolites of N-hydroxylated amidines (amidoximes): synthesis, in vitro formation by pig hepatocytes, and mutagenicity testing. Clement, B., Christiansen, K., Girreser, U. Chem. Res. Toxicol. (2001) [Pubmed]
Reduction of amphetamine hydroxylamine and other aliphatic hydroxylamines by benzamidoxime reductase and human liver microsomes. Clement, B., Behrens, D., Möller, W., Cashman, J.R. Chem. Res. Toxicol. (2000) [Pubmed]
Hepatic, extrahepatic, microsomal, and mitochondrial activation of the N-hydroxylated prodrugs benzamidoxime, guanoxabenz, and Ro 48-3656 ([[1-[(2s)-2-[[4-[(hydroxyamino)iminomethyl]benzoyl]amino]-1-oxopropyl]-4-piperidinyl]oxy]-acetic acid). Clement, B., Mau, S., Deters, S., Havemeyer, A. Drug Metab. Dispos. (2005) [Pubmed]
Metabolism of benzamidoxime (N-hydroxyamidine) in human hepatocytes and role of UDP-glucuronosyltransferases. Fröhlich, A.K., Girreser, U., Clement, B. Xenobiotica (2005) [Pubmed]
Reduction of sulfamethoxazole and dapsone hydroxylamines by a microsomal enzyme system purified from pig liver and pig and human liver microsomes. Clement, B., Behrens, D., Amschler, J., Matschke, K., Wolf, S., Havemeyer, A. Life Sci. (2005) [Pubmed]

Contributions to this collaborative article are from individual authors of WikiGenes or mined by the WikiGenes Data Mining Engine from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenes Open Access Licence Privacy Policy Terms of Use apsburg

The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.