3-(2,6-Dimethylphenyl)-2-Selenoxo-1,3-Thiazolidin-4-One Suppresses Hydrogen Peroxide–Induced Cytotoxicity on PC12 Cells Via Activation of MAPK

Abstract

We newly synthesized organic selenium compounds (5-membered ring compounds) including 2-selenoxo-1,3-thiazolidin-4-ones (compounds A) and 3-alkoxy-4,5-dihydro-5-selenoxo- 1H-1,2,4-triazole-1-carboxylates (compounds B). To address whether these compounds show antioxidative effects, we also examined their superoxide radical (O2−)-scavenging effects. Moreover, we examined the effects of compound Aa on the activation of mitogen-activated protein kinase/extracellular signal-regulated protein kinases (MAPK/ERK1/2) and suppression of hydrogen peroxide-induced cytotoxicity in rat pheochromocytoma cells (PC12 cells). We evaluated the O2−-scavenging activities of the compounds by a chemiluminescence method, and activation of ERK1/2 in PC12 cells was evaluated by Western blot analysis. At 166 μmol/L, the O2−-scavenging activities were markedly different among compounds A and B. 3-(2,6-Dimethylphenyl)-2-selenoxo-1,3-thiazolidin-4-one (compound Aa) exhibited the strongest superoxide anion-scavenging activity among compounds A and B. The concentration necessary for 50% inhibition of the activity (IC50) of compound Aa was 25.9 μmol/L. Compound Aa activated ERK1/2 of the PC12 cell, as did ebselen, and suppressed hydrogen peroxide-induced cytotoxicity more potently than ebselen. In addition, the toxicity of compound Aa was less than that of ebselen. From these results, it is assumed that compound Aa is a candidate drug to prevent oxidative stress-induced cell death.