Chiral sulfoxidation of albendazole by the flavin adenine dinucleotide-containing and cytochrome P450-dependent monooxygenases from rat liver microsomes.
The enantioselectivity of the in vitro sulfoxidation of the prochiral drug albendazole was investigated in rat liver microsomes. When biological material obtained from control rats and phenobarbital-, 3-methylcholanthrene-, or dexamethazone-pretreated rats was subjected to specific immunological and chemical inhibitors, it was shown that two main enzymatic systems--cytochrome P450s and flavin-containing monooxygenase (FMO)--were responsible for the sulfoxidation. Purified FMO from rat liver was used to study the enantioselectivity of this enzyme in the sulfoxidation of albendazole. The enantiospecificity of FMO is the reverse of that of the P450s. Nevertheless, each P450 isoenzyme involved in this reaction presents its own individual stereoselectivity.
Moroni
P
P
Unité de Toxicologie Métabolique et d'Ecotoxicologie, Ecole Vétérinaire de Lyon, Marcy l'Etoile, France.
Buronfosse
T
T
Longin-Sauvageon
C
C
Delatour
P
P
Benoit
E
E
D000367:Age Factors; D015766:Albendazole / Q000378:metabolism*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000302:isolation & purification / Q000378:metabolism; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000302:isolation & purification / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013237:Stereoisomerism; D013454:Sulfoxides / Q000378:metabolism*
D013454:Sulfoxides; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D009251:NADPH-Ferrihemoprotein Reductase; D015766:Albendazole; D010634:Phenobarbital