Microsomal metabolism of 2-(methylseleno) benzanilide.
2-(Methylseleno)benzanilide, a metabolite of ebselen, was oxidatively demethylated by rat liver microsomes to regenerate the parent compound, ebselen. The rate of this novel reaction exceeds that of ring hydroxylation, and it was inhibitable with metyrapone. The sulfur analogue, 2-(methylthio)benzanilide, was oxidized to the corresponding sulfoxide. The regeneration of ebselen from 2-(methylseleno)benzalide is suggested to result from an intermediate selenoxide and hydrolysis with formation of methanol, since only very small amounts of labeled formaldehyde were detected in incubations using 2-[(14C)methylseleno]benzanilide. In an analogous reaction, 2-(benzylseleno)benzaldehyde yielded ebselen upon oxidation with hydrogen peroxide and, as detected by gas-liquid chromatography, benzyl alcohol.
John
N J
NJ
Institut für Physiologische Chemie I, Universität Düsseldorf, FRG.
Terlinden
R
R
Fischer
H
H
Evers
M
M
Sies
H
H
D000813:Anilides / Q000378:metabolism*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism; D001393:Azoles / Q000378:metabolism; D019905:Benzyl Alcohol; D001592:Benzyl Alcohols / Q000378:metabolism; D002250:Carbon Radioisotopes; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005557:Formaldehyde / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D054833:Isoindoles; D008745:Methylation; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism; D016566:Organoselenium Compounds / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000378:metabolism*
D000813:Anilides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001393:Azoles; D001592:Benzyl Alcohols; D002250:Carbon Radioisotopes; D054833:Isoindoles; D016566:Organoselenium Compounds; C071762:2-(methylseleninyl)benzanilide; D005557:Formaldehyde; C071763:2-(methylthio)benzanilide; C042986:ebselen; C068988:2-methylselenobenzanilide; D003577:Cytochrome P-450 Enzyme System; D006861:Hydrogen Peroxide; D012643:Selenium; D019905:Benzyl Alcohol