Bis-(2-amino-5-selenazoyl) Ketone as a Superoxide Anion-Scavenger

Sekiguchi, Akihiro; Nishina, Atsuyoshi; Kimura, Hirokazu; Fukumoto, Ryo-hei; Kogami, Masakazu; Ishihara, Hideharu; Koketsu, Mamoru

doi:10.1248/bpb.29.1404

Cited by 21 publications

(12 citation statements)

References 18 publications

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“…Previously, we systematically synthesized various organic selenium compounds, including selenocarbamates, selenoureas, thioureas, tertiary selenoamide compounds, 2-amino-1,3-selenazoles, and bis-(2-amino-5-selenazoyl) ketones, and demonstrated their SOSA by using the same chemiluminescence method. The IC 50 values of these compounds ranged from approximately 0.1 to 100 µM (Takahashi et al, 2004;Sekiguchi et al, 2005;Takahashi et al, 2005a;Takahashi et al, 2005b;Sekiguchi et al, 2006). The SOSA of compound b might be relatively low compared with that of other compounds such as selenocarbamates, selenoureas, thioureas, tertiary selenoamide, and ebselen.…”

Section: Discussionmentioning

confidence: 97%

A superoxide anion-scavenger, 1,3-selenazolidin-4-one suppresses serum deprivation-induced apoptosis in PC12 cells by activating MAP kinase

Nishina

Kimura

Kozawa

et al. 2011

Toxicology and Applied Pharmacology

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Synthetic organic selenium compounds, such as ebselen, may show glutathione peroxidaselike antioxidant activity and have a neurotrophic effect. We synthesized 1,3-selenazolidin-4-ones, new types of synthetic organic selenium compounds (five-member ring compounds), to study their possible applications as antioxidants or neurotrophic-like molecules. Their superoxide radical scavenging effects were assessed using the quantitative, highly sensitive method of real-time kinetic chemiluminescence. At 166 M, the O2− scavenging activity of 1,3-selenazolidin-4-ones ranged from 0 to 66.2%. 2-[3-(4-Methoxyphenyl)-4-oxo-1,3-selenazolidin-2-ylidene]malononitrile (compound b) showed the strongest superoxide anion-scavenging activity among the 6 kinds of 2-methylene-1,3-selenazolidin-4-ones examined. Compound b had a 50% inhibitory concentration (IC50) at 92.4 M and acted as an effective and potentially useful O2− scavenger in vitro. The effect of compound b on rat pheochromocytome cell line PC12 cells was compared with that of ebselen or nerve growth factor (NGF) by use of the MTT [3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] assay. When ebselen was added at 100 M or more, toxicity toward PC12 cells was evident. On the contrary, compound b suppressed serum deprivation-induced apoptosis in PC12 cells more effectively at a concentration of 100 M. The activity of compound b to phosphorylate mitogen-activated protein kinase/extracellular signal-regulated protein kinase (ERK) 1/2 (MAP kinase) in PC12 cells was higher than that of ebselen, and the former at 100 M induced the phosphorylation of MAP kinase to a degree similar to that induced by NGF. From these results, we conclude that this superoxide anion-scavenger, compound b, suppressed serum deprivationinduced apoptosis by promoting the phosphorylation of MAP kinase. (MAP kinase) in PC12 cells was higher than that of ebselen, and the former at 100 μM induced the phosphorylation of MAP kinase to a degree similar to that induced by NGF.From these results, we conclude that this superoxide anion-scavenger, compound b, suppressed serum deprivation-induced apoptosis by promoting the phosphorylation of MAP kinase.

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Section: Discussionmentioning

confidence: 97%

A superoxide anion-scavenger, 1,3-selenazolidin-4-one suppresses serum deprivation-induced apoptosis in PC12 cells by activating MAP kinase

Nishina

Kimura

Kozawa

et al. 2011

Toxicology and Applied Pharmacology

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“…[15][16][17]30,31 From the results shown in Table 1 A low concentration of O 2 -in the human body generally plays a beneficial role in biological defenses and intercellular signal transduction. 5 On the other hand, excessive O 2 -production is involved in the pathogenesis of a number of disorders, including inflammation, rheumatoid arthritis and asthma.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2011

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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 mol/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 mol/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. 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.

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“…Selenium-containing organic compounds can be used in cancer therapy [12][13][14][15][16][17][18][19][20][21], in particular as cancer cell proliferation inhibitors [22][23][24][25][26][27][28][29][30][31][32], and they exhibit antihypertensive [33], antibacterial [13,[34][35][36][37][38][39], antifungal [40,41], antiparasitic [42], and antimicrobial activity [43]. During the past decade various selenium derivatives have been tested for biological activity as free radical [44][45][46] and superoxide anion scavengers [47], antioxidants [48][49][50][51][52][53], anti-inflammatory agents, and microglial activation inhibitors [54]. The possibility of using organoselenium compounds in the treatment of AIDS has been studied [55].…”

Section: Introductionmentioning

confidence: 99%