Antioxidant activity and low toxicity of (E)-1-(1-(methylthio)-1-(selenopheny) hept-1-en-2-yl) pyrrolidin-2-one

Abstract

The aim of the present study was to evaluate the potential pharmacological and toxicological properties of (E)-1-(1-(methylthio)-1-(selenopheny) hept-1-en-2-yl) pyrrolidin-2-one (compound 1), an organoselenium compound. In vitro experiments showed that compound 1 presented a reduction in the lipid peroxidation induced by Fe²⁺ in thiobarbituric acid-reactive species (TBARS) production, and in the generation of reactive species caused by Fe²⁺/malonate in DCFH-DA oxidation. The high dose (500 mg/kg) induced an increase on ALT but not on AST activity. Hepatic, but not cerebral, δ-ALA-D activity from mice treated with 500 mg/kg presented a significant inhibition. Brain catalase activity was significantly inhibited by 100 mg/kg whereas hepatic catalase activity showed a significant increase at all doses. Hepatic lipid peroxidation was diminished only at lowest dose (100 mg/kg) whereas for brain tissue, all doses induced a significant reduction in TBARS levels. Brain and liver ascorbic acid contents were increased only at highest dose of compound 1. Urea and creatinine levels were not significantly altered by treatments. This is a promising compound with antioxidant activity and low toxicity, suggesting the potential beneficial activity of compound 1 against oxidative damage in many parameters studied in rats and mice.

The potential toxicological insights about the anti-HIV drug azidothymidine-derived monoselenides in human leukocytes: Toxicological insights of new selenium-azidothymidine analogs

“…[16][17][18] This amino acid is present in selenoproteins and selenoenzymes, such as glutathione peroxidase (GPx) and thioredoxin reductase (TrxR), which are involved in the maintenance of equilibrium between the production and decomposition of reactive oxygen species (ROS) in the body. [19][20][21] In the last four decades, the synthesis and the search for new organoselenium compounds with potential antioxidant properties have been increased (for comprehensive review, see literatures [22][23][24][25][26] ). Ebselen and diphenyl diselenide, two organoselenium compounds that have been extensively studied in the literature, [22][23][24][25][26] present antioxidant effects in different in vitro and in vivo models associated with OS.…”

“…[19][20][21] In the last four decades, the synthesis and the search for new organoselenium compounds with potential antioxidant properties have been increased (for comprehensive review, see literatures [22][23][24][25][26] ). Ebselen and diphenyl diselenide, two organoselenium compounds that have been extensively studied in the literature, [22][23][24][25][26] present antioxidant effects in different in vitro and in vivo models associated with OS. The mechanisms involved in their antioxidant activity are related to their transformation to selenol intermediates (see Online Supplementary content 1) either via their direct reduction by endogenous reduced thiols (normally glutathione, pathway 2 in Online Supplementary content 1) or via a catalyzed reaction involving TrxR (pathway 1 in Online Supplementary content 1).…”