Potential cancerostatic benfluron is metabolized by peroxidase: in vitro biotransformation of benfluron by horseradish peroxidase.
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.
Hrubý
K
K
Institute of Experimental Biopharmaceutics, PRO.MED.CS. Praha & Academy of Sciences, Hradec Králové, Czech Republic.
Anzenbacherová
E
E
Anzenbacher
P
P
Nobilis
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003640:Dealkylation; D005449:Fluorenes / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D006735:Horseradish Peroxidase / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D010105:Oxygenases / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism
D000970:Antineoplastic Agents; D005449:Fluorenes; C034234:VUFB 13468; D003577:Cytochrome P-450 Enzyme System; D006735:Horseradish Peroxidase; D010544:Peroxidases; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)