Efficient Synthesis of Modular Amino Acid Derivatives Containing Selenium with Pronounced GPx‐Like Activity

Alberto, Eduardo E.; Soares, Letiére C.; Sudati, Jéssie Haigert; Borges, Antonio C. A.; Rocha, João Batista Teixeira da; Braga, Antônio L.

doi:10.1002/ejoc.200900485

Cited by 61 publications

(14 citation statements)

References 52 publications

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“…19 It was observed that the influence of the chain length between the diselenide moiety and amino acid residue played a crucial role in modulating the GPx like activity of the tested diselenides. Compounds 18c and 18b derived from L-phenylalanine with a longer chain length, showed better results than PhSe) 2 , while compound 18a, with a shorter chain length, was the least effective catalyst screened.…”

Section: Organoselenium Compoundsmentioning

confidence: 99%

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Catalytic application of selenium and tellurium compounds as glutathione peroxidase enzyme mimetics

Alberto¹,

Nascimento²,

Braga³

2010

J. Braz. Chem. Soc.

139

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A glutationa peroxidase (GPx) é uma importante enzima que faz parte do sistema de defesa do organismo frente a substâncias nocivas formadas durante o metabolismo do oxigênio, como peróxidos e seus derivados. Diversas estratégias para desenvolver novos miméticos, assim como para aumentar a atividade mimética da GPx em compostos como disselenetos, selenetos e teluretos, vêm sendo propostas nos últimos anos. Nesta revisão é apresentado um balanço, dos últimos dez anos, referente ao desenvolvimento e à avaliação de catalisadores organoselênio ou organotelúrio capazes de mimetizar a atividade da GPx. Diferentes mecanismos de ação destes compostos também são apresentados, de acordo com os novos avanços desta relevante área de pesquisa.This review covers the past decade of intensive research on the design, synthesis and screening of organoselenides and tellurides as catalyst able to mimic the activity of the selenoenzyme glutathione peroxidase (GPx). This important enzyme forms part of the detoxification system in humans which deals with harmful peroxides and their byproducts formed during oxygen metabolism. Several strategies to enhance the GPx-like activity of compounds such as diselenides, selenides and tellurides have been proposed in recent years. Different mechanisms of action of these compounds are also presented in this review highlighting new advances in this exciting research field.

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Section: Organoselenium Compoundsmentioning

confidence: 99%

“…In 2009, Braga et al 19 described the synthesis of compounds 18a-c, a new class of chiral diselenides derived from amino acids. 19 It was observed that the influence of the chain length between the diselenide moiety and amino acid residue played a crucial role in modulating the GPx like activity of the tested diselenides.…”

Section: Organoselenium Compoundsmentioning

confidence: 99%

Catalytic application of selenium and tellurium compounds as glutathione peroxidase enzyme mimetics

Alberto¹,

Nascimento²,

Braga³

2010

J. Braz. Chem. Soc.

139

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“…The first synthetic organoselenium compound was ebselen (2‐phenyl‐1,2‐benzisoselenazol‐3‐(2 H )one), which mimics the GPx catalytic activity both in vivo and in vitro . Successively, a number of selenium‐containing small molecules have been developed, either by modifying the basic structure of ebselen or by incorporating some structural features of the native enzyme . Substitution of selenium by tellurium in a series of diarylchalcogenides results in a pronounced increase in antioxidant activity as suggested by several authors …”

Section: Introductionmentioning

confidence: 99%

“…[4][5][6] Successively,anumber of selenium-containing smallm olecules have been developed, eitherb ym odifying the basic structure of ebselen or by incorporating somes tructuralf eatures of the nativee nzyme. [7][8][9][10][11][12][13][14][15][16][17][18][19][20] Substitution of seleniumb yt ellurium in a series of diarylchalcogenides results in ap ronouncedi ncrease in antioxidant activity as suggested by several authors. [21][22][23] Stimulated by the numerous interesting biological activities of the ebselena nd its derivatives, many researchers have associated the presence of chalcogen in the aromatic ring, containing conjugativee lectron-donating substituents (OH, NH 2 , NMe 2 ,N HPh), to the reduction of t 50 values (time required to reducet he thiol concentration by 50 %).…”

Section: Introductionmentioning

confidence: 99%

Chemical Insights into the Antioxidant Mechanisms of Alkylseleno and Alkyltelluro Phenols: Periodic Relatives Behaving Differently

Marino

Galano

Mazzone

et al. 2018

Chemistry A European J

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The possible antioxidant reaction mechanisms of recently synthesized and tested alkylseleno (telluro) phenols have been explored using density functional theory by considering two solvents physiologically relevant, water and pentylethanoate (PE). In addition, the possible pathway for the antioxidant regeneration with ascorbic acid has been investigated. Results show that selenium and tellurium systems follow different chemical behaviors. In particular, the alkylseleno phenol (ebselenol) antioxidant activity is justified through a sequential proton loss-electron-transfer mechanism in water media, whereas in PE the hydrogen-atom transfer process is favored. In the case of the tellurium derivative, the oxygen-transfer mechanism represents the preferential one. Furthermore, electronic properties have been analyzed to rationalize the different reactivity of the selenium- and tellurium-containing systems. To confirm the results, smaller but similar systems were also investigated. The calculated data support the different mechanism (Se vs. Te) proposals.

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“…The compound studied on the present work, (S )-dimethyl 2-(3-(phenyltellanyl) propanamido) succinate (TeAsp), is a new telluroamino acid derivative of aspartic acid that was found to be the most potent mimetic of GPx among 20 newly synthesized derivatives (Braga et al 2009; Alberto et al 2009) presenting antioxidant properties in vitro . However, when administered to rodents this compound showed potent genotoxic and mutagenic actions (Meinerz et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Sub-acute administration of (S)-dimethyl 2-(3-(phenyltellanyl) propanamido) succinate induces toxicity and oxidative stress in mice: unexpected effects of N-acetylcysteine

et al. 2013

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The organic tellurium compound (S)-dimethyl 2-(3-(phenyltellanyl) propanamide) succinate (TeAsp) exhibits thiol-peroxidase activity that could potentially offer protection against oxidative stress. However, data from the literature show that tellurium is a toxic agent to rodents. In order to mitigate such toxicity, N-acetylcysteine (NAC) was administered in parallel with TeAsp during 10 days. Mice were separated into four groups receiving daily injections of (A) vehicle (PBS 2.5 ml/kg, i.p. and DMSO 1 ml/kg, s.c.), (B) NAC (100 mg/kg, i.p. and DMSO s.c.), (C) PBS i.p. and TeAsp (92.5 μmol/kg, s.c), or (D) NAC plus TeAsp. TeAsp treatment started on the fourth day. Vehicle or NAC-treated animals showed an increase in body weight whereas TeAsp caused a significant reduction. Contrary to expected, NAC co-administration potentiated the toxic effect of TeAsp, causing a decrease in body weight. Vehicle, NAC or TeAsp did not affect the exploratory and motor activity in the open-field test at the end of the treatment, while the combination of NAC and TeAsp produced a significant decrease in these parameters. No DNA damage or alterations in cell viability were observed in leukocytes of treated animals. Treatments produced no or minor effects on the activities of antioxidant enzymes catalase, glutathione peroxidase and glutathione reductase, whereas the activity of the thioredoxin reductase was decreased in the brain and increased the liver of the animals in the groups receiving TeAsp or TeAsp plus NAC. In conclusion, the toxicity of TeAsp was potentiated by NAC and oxidative stress appears to play a central role in this process.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-2-182) contains supplementary material, which is available to authorized users.

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Efficient Synthesis of Modular Amino Acid Derivatives Containing Selenium with Pronounced GPx‐Like Activity

Cited by 61 publications

References 52 publications

Catalytic application of selenium and tellurium compounds as glutathione peroxidase enzyme mimetics

Catalytic application of selenium and tellurium compounds as glutathione peroxidase enzyme mimetics

Chemical Insights into the Antioxidant Mechanisms of Alkylseleno and Alkyltelluro Phenols: Periodic Relatives Behaving Differently

Sub-acute administration of (S)-dimethyl 2-(3-(phenyltellanyl) propanamido) succinate induces toxicity and oxidative stress in mice: unexpected effects of N-acetylcysteine

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