Microsomal metabolism of 2-(methylseleno)benzanilide

Abstract

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.

Antioxidant Activity of the Anti‐Inflammatory Compound Ebselen: A Reversible Cyclization Pathway via Selenenic and Seleninic Acid Intermediates

“…The selenoxide 19 was prepared by following the literature method. [36] Synthesis of 9: Aqueous 30 % H 2 O 2 (41 mL, 0.36 mmol) was added to a stirred solution of ebselen (0.1 g, 0.36 mmol) in CH 2 Cl 2 (10 mL). The reaction mixture was stirred for 24 h at ambient temperature.…”

“…A similar reaction involving the elimination of methanol has been proposed for the formation of ebselen from the methyl selenoxide 19 (Scheme 8). [36] To confirm the formation of ebselen from compound 19 at higher temperatures, we have synthesized the selenoxide 19 from 2-methyl selenobenzanilide, which is one of the metabolites of ebselen in vivo. The crystal structure of 19 shows the existence of noncovalent interactions between the selenium and carbonyl oxygen atoms (Se···O: 2.69 ), although the interaction is found to be weaker than that of 9.…”

DEACTIVATION OF SINGLET MOLECULAR OXYGEN BY ORGANO‐SELENIUM COMPOUNDS EXHIBITING GLUTATHIONE PEROXIDASE ACTIVITY and BY SULFUR‐CONTAINING HOMOLOGS*

“…Perdeuterated methanol and benzene were purchased from CEA (Comissariat a I'Energie Atomique, Saclay, France) and meso-tetra (4-N-sulphonatophenyl) porphin (TPPTS) from Porphyrin Products, Logan, UT. The selenium and sulfur organic compounds were synthe- sized as described: la by Fischer and Dereu (1987), l b by McClelland and Gait (1926), lc, Id and If by Lambert (1987), l e by Dakova et al (1991), 2a by Lambert et al (1987), 2b by Uchida and Kozuka (1981), 2c by John et al (1990) and 2d by Gialdi et al (1960). Their structures are shown in Fig.…”

Synthesis and Characterization of a New Five and Six Membered Selenoheterocyclic Compounds Homologues of Ebselen

“…(16). This compound was obtained as green oil; yield 52%, IR (NaCl) ν max absence of (C=O), 1 (20). To a solution of hydrazide 19 (1 mmol) in dichloroethane (20 mL), bromine (3 mmol) was added with stirring for a period of 2 h at 0…”

“…On the other hand, Ebselen contains a selenic moiety stabilized by intramolecular cyclisation in a cyclic N-aroyl selenamide and does not release selenium, as demonstrated by a 75 Se-labeling study, which result in its relatively nontoxic properties [16,17]. The discovery of its anti-inflammatory and glutathione-peroxidase (GPx)-like activity has initiated numerous biochemical and pharmacological investigations as well as clinical trials as an antioxidant [18][19][20][21]. Similarly a study of the mechanism of the (GPx)-like activity of Ebselen has shown the formation in a catalytic cycle of various intermediates constituting different oxidation levels of the selenium atom [22,23].…”