S-oxidation of (+)-cis-3,5-dimethyl-2-(3-pyridyl)-thiazolidin-4-one hydrochloride by rat hepatic flavin-containing monooxygenase 1 expressed in yeast.
1. Rat hepatic flavin-containing monooxygenase 1 (FMO1) expressed in yeast catalyzed the S-oxidation of (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502) in vitro. 2. S-oxidation was inhibited by 1-(1-naphthyl)-2-thiourea and thiobenzamide, known inhibitors of FMO, but was not enhanced by n-octylamine, a known enhancer of FMO. 3. The rate of S-oxide formation from SM-12502 was about four-fold lower than that from (+/-)-trans-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-9979) and enantioselectivity and diastereoselectivity of the S-oxidation reaction were observed. 4. The ability of the recombinant yeast to produce the S-oxide from SM-12502 was maintained for long periods and exemplifies the recombinant yeast as a bioreactor to produce a large amount of the S-oxide.
Nunoya
K
K
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Yokoi
T
T
Itoh
K
K
Itoh
S
S
Kimura
K
K
Kamataki
T
T
D000818:Animals; D006863:Hydrogen-Ion Concentration; D008862:Microsomes, Liver / Q000201:enzymology*; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000235:genetics / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D013844:Thiazoles / Q000378:metabolism*; D053778:Thiazolidines
D010972:Platelet Activating Factor; D011994:Recombinant Proteins; D013844:Thiazoles; D053778:Thiazolidines; C065776:3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)