Potential cancerostatic benfluron is metabolized by peroxidase: in vitro biotransformation of benfluron by horseradish peroxidase

Gen Physiol Biophys. 1997 Dec;16(4):321-7.

Abstract

Horseradish peroxidase (HRP) was used to investigate whether benfluron (a potential cytostatic drug) can be biotransformed extra-hepatically by systems other than flavin-containing monooxygenase and cytochromes P450. Three types of incubation mixtures differing in buffers (Na-phosphate buffer 50 mmol/l, pH 6.8 and 8.4 and Tris-HCl buffer 25 mmol/l, pH 7.5) were tested. The amount of N-demethylated benfluron (demB) formed was significantly higher (up to 4 times in the Na-phosphate buffer, pH 8.4, and 5 times in the Na-phosphate buffer, pH 6.8, and in the Tris-HCl buffer, pH 7.5) compared to control experiments. The highest yields of demB were obtained with the moderately alkaline Na-phosphate buffer (50 mmol/l, pH 8.4). The concentration of demB increased during thirty minutes of incubation, and then remained constant through the end of two-hour incubation. The results support the hypothesis that benfluron can be metabolized extra-hepatically by N-demethylation reaction catalyzed by peroxidases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism*
  • Antineoplastic Agents / pharmacokinetics
  • Biotransformation
  • Cytochrome P-450 Enzyme System / metabolism
  • Dealkylation
  • Fluorenes / chemistry
  • Fluorenes / metabolism*
  • Fluorenes / pharmacokinetics
  • Horseradish Peroxidase / metabolism
  • Humans
  • In Vitro Techniques
  • Models, Biological
  • Oxygenases / metabolism
  • Peroxidases / metabolism

Substances

  • Antineoplastic Agents
  • Fluorenes
  • VUFB 13468
  • Cytochrome P-450 Enzyme System
  • Horseradish Peroxidase
  • Peroxidases
  • Oxygenases
  • dimethylaniline monooxygenase (N-oxide forming)