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

• Published in: General physiology and biophysics Vol. 16; no. 4; pp. 321 - 327
• Main Authors: Hrubý, K, Anzenbacherová, E, Anzenbacher, P, Nobilis, M
• Format: Journal Article
• Language: English
• Published: Slovakia 01.12.1997
• Subjects: 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
• ISSN: 0231-5882

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.