CHARACTERIZATION AND PARTIAL PURIFICATION OF THE RAT AND HUMAN ENZYME SYSTEMS ACTIVE IN THE REDUCTION OF N-HYDROXYMELAGATRAN AND BENZAMIDOXIME

@article{Andersson2005CHARACTERIZATIONAP,
  title={CHARACTERIZATION AND PARTIAL PURIFICATION OF THE RAT AND HUMAN ENZYME SYSTEMS ACTIVE IN THE REDUCTION OF N-HYDROXYMELAGATRAN AND BENZAMIDOXIME},
  author={Susanne Andersson and Yvonne Hofmann and {\AA}sa Nordling and Xue-Qing Li and Sabina Nivelius and Tommy B. Andersson and Magnus Ingelman-Sundberg and Inger Johansson},
  journal={Drug Metabolism and Disposition},
  year={2005},
  volume={33},
  pages={570 - 578}
}
The enzymic basis for intracellular reduction of N-hydroxylated amidines to their corresponding amidines, and hydroxylamines to their corresponding amines, is unknown. The hydroxylated amidines can be used as prodrug moieties, and an understanding of the enzyme system active in the reduction can contribute to more efficient drug development. In this study, we examined the properties of this enzyme system using benzamidoxime and N-hydroxymelagatran as substrates. In rats and humans, the hepatic… Expand
Identification of the Missing Component in the Mitochondrial Benzamidoxime Prodrug-converting System as a Novel Molybdenum Enzyme*
TLDR
The 35-kDa protein represents a novel group of molybdenum proteins in eukaryotes as it forms the catalytic part of a three-component enzyme complex consisting of separate proteins in the outer mitochondrial membrane. Expand
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)
TLDR
Results demonstrate that in addition to the microsomal reduction, mitochondria are involved to a great extent in the activation of amidoxime prodrugs. Expand
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TLDR
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1. This study investigates the enzymatic reduction of N-hydroxylated amidines by porcine adipose tissue and the possible involvement of stearoyl-CoA desaturase (SCD). 2. The reduction of the modelExpand
Diacetyldiamidoximeester of Pentamidine, a Prodrug for Treatment of Protozoal Diseases: Synthesis, in vitro and in vivo Biotransformation
TLDR
The objectives of this investigation were the synthesis of all potential metabolites of the double prodrug, the conformational analysis of its structure, and to study the in’vitro and in vivo biotransformation by ester cleavage and N‐reduction to pentamidine via four intermediate metabolites. Expand
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TLDR
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TLDR
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Results indicate that cytochrome b5 and b5 reductase play a direct role in metabolic activation of DB289 to furamidine. Expand
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