A Novel Glutathione Peroxidase Mimic with Antioxidant Activity

Ren, Xiaojun; Yang, Liquan; Liu, Junqiu; Su, Dan; You, Delin; Liu, Chuanpen; Zhang, Kun; Luo, Gaoxing; Mu, Ying; Yan, Ganglin; Shen, Jiacong

doi:10.1006/abbi.2000.2238

Cited by 46 publications

(25 citation statements)

References 39 publications

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“…Many diseases and degenerative processes can be associated with the overproduction of reactive oxygen species, including inflammation, brain ischemia, mutagenesis, cancer, dementia and physiological aging (Ren et al, 2001). Because of this, the interest of the scientific community in natural and synthetic antioxidant compounds that could retard the development of these diseases has grown considerably in recent decades.…”

Section: Discussionmentioning

confidence: 99%

Vinylic telluride derivatives as promising pharmacological compounds with low toxicity

Borges

Savegnago

Pinton

et al. 2008

J of Applied Toxicology

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The aim of the present study was to evaluate pharmacological and toxicological properties of (Z)-2-(methylthio)-1-(butyltelluro)-1-phenylethene 1a, (Z)-1-(4-methylphenylsulfonyl)-2-(phenyltelluro)-2-phenylethene 1b, (Z)-2-(butyltelluro)-1-(benzylthio)-1-heptene 1c and (Z)-2-(phenylthio)-1-(butyltelluro)-1-phenylethene 1d. In vitro, vinylic telluride derivatives 1a, 1d and 1c were more effective in reducing lipid peroxidation than compound 1b. The maximal inhibitory effect of vinylic telluride derivatives on lipid peroxidation was in the following order: 1a = 1d > 1c > 1b. Compound 1b was more potent in inhibiting delta-ALA-D activity (delta-aminolevulinate dehydratase) than compounds 1c and 1d. Based on the in vitro properties presented by compounds 1a (an antioxidant) and 1b (a pro-oxidant), toxicological parameters were assessed in vivo and ex vivo in rats. Calculated LD50 of compounds 1a and 1b, administered by oral route, were 20.5 and 1.44 micromol kg(-1), respectively. Compound 1b induced behavioral alterations in the open field test. Renal and spleenic delta-ALA-D activities were inhibited in rats treated orally with compound 1a. Compound 1b stimulated delta-ALA-D activity in liver and spleen of rats. Rats treated with compound 1b had increased hepatic, renal and spleenic lipid peroxidation. Renal and hepatic markers were not altered when compounds 1a and 1b were administered to rats at doses of around LD50, while compound 1a at high doses changed aspartate aminotransferase activity and urea levels. Based on in vitro results, this study demonstrated that compounds 1a and 1d are promising antioxidant compounds. Ex vivo data reinforce compound 1a as a promising drug for more detailed pharmacological studies.

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Section: Discussionmentioning

confidence: 99%

Vinylic telluride derivatives as promising pharmacological compounds with low toxicity

Borges

Savegnago

Pinton

et al. 2008

J of Applied Toxicology

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“…The solution was treated with 1 M imidazole to quench the excess reducing reagent and adjusted to pH 7.0 with 1 M HCl, then 50 μL of the solution was added to 950 μL DTNB solution (0.1 mM). The concentration of selenol in the mimic was determined by adding, and measuring the absorption of, 3-carboxy-4-nitrobenzenethiolate at 410 nm (ε = 11,400 M -1 cm -1 ) [14].…”

Section: Preparation Of Mn(iii) 2 (L-se-so 3 Na)mentioning

confidence: 99%

“…However, Wilson et al [11] introduced a quaternary ammonium salt close to a diselenide bridge in a synthetic GPX mimic in order to improve the binding of reduced glutathione (GSH) by electrostatic attraction, and this was found to increase the hydroperoxide-reducing activity substantially, thus demonstrating that affinity for GSH is essential for effective GPX imitation. Under this theory, other analogues of GPX have also been produced, including selenium-containing cyclodextrin (SeCD) [12][13][14], bio-imprinted protein [15], catalytic antibodies [16] and semi-synthetic enzymes [17]. Some of these have demonstrated similar activity to GPX.…”

Section: Introductionmentioning

confidence: 96%

Synthesis and kinetic evaluation of a trifunctional enzyme mimic with a dimanganese active centre

Gao

et al. 2011

Journal of Inorganic Biochemistry

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“…They attack essential cell constituents, such as proteins, lipids, and nucleic acids, leading to the formation of toxic compounds (Kahraman et al 2003). Many diseases and degenerative processes can be associated with the overproduction of ROS, including inflammation, brain ischemia, mutagenesis, cancer, dementia, and physiological aging (Ren et al 2001). …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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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.

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A Novel Glutathione Peroxidase Mimic with Antioxidant Activity

Cited by 46 publications

References 39 publications

Vinylic telluride derivatives as promising pharmacological compounds with low toxicity

Vinylic telluride derivatives as promising pharmacological compounds with low toxicity

Synthesis and kinetic evaluation of a trifunctional enzyme mimic with a dimanganese active centre

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

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