[Show abstract][Hide abstract] ABSTRACT: Hepatic encephalopathy is a common complication of severe acute hepatic failure and has been associated with high short-term mortality rates. Therefore, the aim of this study was to investigate the effect of diphenyl diselenide (DPDS) and its analogues in protecting against thioacetamide (TAA)-induced acute neurological and hepatic failure in mice. The animals received a TAA dose of 200 mg kg−1 intraperitoneally, and then, 1 hour later, they received 15.6 mg kg−1 of diselenides intraperitoneally. Twenty three hours after diselenide administration, the animals were sacrificed, and blood, brain and liver samples were collected for analysis. The results showed that mice exposed to TAA presented oxidative stress characteristics, such as an increase in lipid peroxidation (LPO), enhanced glutathione peroxidase activity and a decrease in the GSH/GSSH ratio in the brain and liver. In addition, the TAA group showed a decrease in cellular viability in both tissues. TAA treatments also generate reactive oxygen species and cause inhibition of glutathione-S-transferase in liver, which were associated with TAA exacerbated half-life in this tissue. In the histopathological analyses, we observed that TAA induced a large inflammation process that was confirmed according to the elevation of liver myeloperoxidase activity. Moreover, the treatment with diselenides reduced the oxidative stress significantly. Additionally, after the establishment of acute hepatic failure (AHF), DPDS was able to inhibit the inflammatory processes with a more significant decrease in major hepatic damage effects than was presented after treatment with its analogues. Thus, our results showed that DPDS is a promising therapeutic option for the treatment of AHF and hepatic encephalopathy as mice returned to normal conditions after the damage.
[Show abstract][Hide abstract] ABSTRACT: A new magnetically recoverable nanocatalyst was prepared by coating magnetite with niobium oxide (Fe3O4@Nb2O5) by using a simple wet impregnation method. The Fe3O4@Nb2O5 nanocatalyst was fully characterized, and its catalytic activity was evaluated by using the one-pot, three-component Biginelli reaction, with the aim to synthesize 1,4-dihydropyrimidinones, a class of compounds with diverse pharmacological properties. The developed protocol was applied to a wide range of aliphatic and aromatic substrates, and structurally diverse products were obtained in excellent yields. Compared with copper and nickel nanocatalysts, the Fe3O4@Nb2O5 nanocatalyst demonstrated superior catalytic activity at a remarkably low catalyst loading (0.1 mol %). This niobium nanocatalyst could be easily separated from the reaction mixture with an external magnet and was reused several times without any loss of its catalytic activity. Moreover, although the Biginelli reaction is a century-old reaction, its mechanism is still a controversial subject, and our investigation provided an insight into the reaction mechanism.
[Show abstract][Hide abstract] ABSTRACT: Anxiety-related disorders are frequently observed in the population. Because the available pharmacotherapies for anxiety can cause side effects, new anxiolytic compounds have been screened using behavioral tasks. For example, diphenyl diselenide (PhSe)2, a simple organoselenium compound with neuroprotective effects, has demonstrated anxiolytic effects in rodents. However, this compound has not yet been tested in a novelty-based paradigm in non-mammalian animal models. In this study, we assessed the potential anxiolytic effects of (PhSe)2 on the behavior of adult zebrafish under novelty-induced stress. The animals were pretreated with 0.1, 0.25, 0.5, and 1μM (PhSe)2 in the aquarium water for 30min. The fish were then exposed to a novel tank, and their behavior was quantified during a 6-min trial. (PhSe)2 treatment altered fish behavior in a concentration-dependent manner. At 0.01 and 0.25μM, (PhSe)2 did not elicit effects on fish behavior. At 0.5μM, moderate behavioral side effects (e.g., lethargy and short episodic immobility) were noted. At the highest concentration tested (1μM), dramatic side effects were observed, such as burst behavior and longer periods of immobility. The results were confirmed by spatiotemporal analysis of each group. Occupancy plot data showed dispersed homebase formation in the 0.25μM (PhSe)2-treated group compared with the control group (treated with 0.04% DMSO). Furthermore, animals treated with 0.25μM (PhSe)2showed a reduction in latency to enter the top and spent more time in the upper area of the tank. These data suggest that (PhSe)2 may induce an anxiolytic-like effect in situations of anxiety evoked by novelty.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 06/2014; 54. DOI:10.1016/j.pnpbp.2014.06.002 · 4.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report an efficient, fast, and environmentally friendly method for the synthesis of a wide range of thiol esters using stable diorganoyl disulfides and acyl chlorides, using CuO nanoparticles and [pmim]Br as the reductive system. This method gave good to excellent isolated yields of the desired products after only three minutes of microwave irradiation. Furthermore, by using the same green approach, we were also able to synthesize thiocarbonates bearing interesting functionalities.
European Journal of Organic Chemistry 08/2013; 2013(23). DOI:10.1002/ejoc.201300295 · 3.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The synthesis of new chiral seleno-, telluro-, and thio-N-Boc-γ-amino acids is described herein. These new compounds were prepared through a simple and short synthetic route, from the inexpensive and commercially-available amino acid l-glutamic acid. The products, with a highly modular character, were obtained in good to excellent yields, via hydrolysis of chalcogen pyroglutamic derivatives with overall retention of the l-glutamic acid stereochemistry. Also, an l-diselenide-N-Boc-γ-amino acid was prepared in good yield. This new synthetic route represents an efficient method for preparing new l-chalcogen- and l-diselenide-γ-amino acids with biological potential.
[Show abstract][Hide abstract] ABSTRACT: This study was designed to examine the antioxidant activity in vitro of novel mono- and diselenide compounds. We compared whether the formation of p-methyl-selenol from compounds 1-phenyl-3-(p-tolylselanyl)propan-2-amine (C1) and 1,2-dip-tolyldiselenide (C4) and o-methoxy-selenol from compounds 1-(2-methoxyphenylselanyl)-3-phenylpropan-2-amine (C2) and 1,2-bis(2-methoxyphenyl)diselenide (C3) may be involved in their antioxidant effects. The compounds were tested against Fe(II) and sodium nitroprusside (SNP)-induced lipid peroxidation in rat brain and liver homogenates. Likewise, the antioxidant capacity of the compounds was assessed by their ability to decolorize the DPPH radical as well as the Fe(II) chelating assay through the reduction of molybdenum(VI) (Mo6+) to molybdenum(V) (Mo5+). This colorimetric assay was also used to quantify thiol peroxidase (GPx) and oxidase activity and thioredoxin reductase (TrxR) activity. The results showed that the novel selenide compounds inhibit the thiobarbituric acid reactive species (TBARS) induced by different pro-oxidants, but the monoselenides effects were significant only at concentrations higher than the concentrations of the diselenides. Similarly, the total antioxidant activity was higher in the diselenides. Moreover, GPx and TrxR activity was only observed for the diselenides, which indicates that these compounds are more stable selenol molecules than monoselenides.
Toxicology in Vitro 03/2013; 27(5). DOI:10.1016/j.tiv.2013.03.001 · 3.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The synthesis of new chiral non-natural seleno-, thio-, and telluro-peptides is described herein. These new compounds were prepared through simple and brief synthetic route, from inexpensive and commercially available amino acids. The products, possessing a highly modular character, were obtained in good to excellent yields (50–96%), via ring opening of aziridines with chalcogenolate anions, generated using indium(I) iodide as a reducing agent.
[Show abstract][Hide abstract] ABSTRACT: A series of chiral β-seleno amino derivatives were synthesized via a ring opening reaction of different aziridines with diorganyl diselenides mediated by recyclable CuO nanopowder and an ionic liquid affording the corresponding products in good to excellent yields. The [bmim]BF4 ionic liquid acts as both promoter and reaction medium. Compared to the usual organic solvents the ionic liquid exhibited better performance with the advantage of its recyclability.
[Show abstract][Hide abstract] ABSTRACT: The ephedrine-based diselenide appears as a new promiscuous catalyst, able to generate optically active alcohols by addition of organozinc to aldehydes (up to 97% ee), and shows powerful GPx like activity, reducing H(2)O(2) to water in only 16.33 min (eleven times faster than PhSeSePh).
[Show abstract][Hide abstract] ABSTRACT: The antioxidant properties of organoselenium compounds have been extensively investigated because oxidative stress is a hallmark of a variety of chronic human diseases. Here, we reported the influence of substituent groups in the antioxidant activity of β-selenoamines. We have investigated whether they exhibited glutathione peroxidase-like (GPx-like) activity and whether they could be substrate of thioredoxin reductase (TrxR). In the DPPH assay, the β-selenium amines did not exhibit antioxidant activity. However, the β-selenium amines with p-methoxy and tosyl groups prevented the lipid peroxidation. The β-selenium amine compound with p-methoxy substituent group exhibited thiol-peroxidase-like activity (GPx-like activity) and was reduced by the hepatic TrxR. These results contribute to understand the influence of structural alteration of non-conventional selenium compounds as synthetic mimetic of antioxidant enzymes of mammalian organisms.
[Show abstract][Hide abstract] ABSTRACT: A recyclable copper nanopowder catalyst in ionic liquid is effective for promotion of the cross-coupling reaction of various thiols with aryl iodides under ligand-free conditions. Compared to the usual organic solvents, [bmmim]BF4 exhibited higher performance with the advantage of being able to be reused for up to four successive runs.
[Show abstract][Hide abstract] ABSTRACT: An efficient method is presented for the synthesis of chiral β-seleno amines via ring-opening reaction of aziridines (I) using zinc selenoate (II) as nucleophile.
[Show abstract][Hide abstract] ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
[Show abstract][Hide abstract] ABSTRACT: The synthesis of selenium- and tellurium-containing nucleosides, derived from uridine is described herein. These compounds were prepared in a concise and short synthetic route in good yields, by nucleophilic substitution of a tosylate group by organoselenium nucleophiles.
[Show abstract][Hide abstract] ABSTRACT: DNA damage and cell viability of human leukocytes cells were examined as simple tests for screening the potential toxicity of organoselenium compounds. Leukocytes were incubated with different organoselenium compounds at 4, 10, 40 and 100 microM or vehicle (DMSO) for 3h at 37 degrees C before of in vitro assays. Cell viability was determined by Trypan blue exclusion. DNA damage was assessed using the alkaline comet assay with silver staining. The exposure of leukocytes to (S)-tert-butyl 1-diselenide-3-methylbutan-2-ylcarbamate, (S)-tert-butyl 1-diselenide-3-phenylpropan-2-ylcarbamate, (S)-2-amino-1-diselenide-3-methylpropanyl, (S)-2-amino-1-diselenide-3-phenylpropanyl, 3',3-ditrifluoromethyl diphenyl diselenide, 4',4-dimethoxy diphenyl diselenide, 4',4-dichloro diphenyl diselenide and 2',2,4',4,6',6-hexamethyl diphenyl diselenide, in the range of 10-100muM, induced a significant increase in Damage Index (DI). The genotoxic effect of all compounds was associated with high frequencies of cells with damage level 4 and all compounds caused a decrease in cell viability. Our results suggest that the selenium compounds tested were genotoxic and cytotoxic to human leukocytes cells in vitro and that the organoselenium amino acid derivatives ((S)-tert-butyl 1-diselenide-3-methylbutan-2-ylcarbamate, (S)-tert-butyl 1-diselenide-3-phenylpropan-2-ylcarbamate, (S)-2-amino-1-diselenide-3-methylpropanyl and (S)-2-amino-1-diselenide-3-phenylpropanyl) were more genotoxic than aromatic derivatives (3',3-ditrifluoromethyl diphenyl diselenide, 4',4-dimethoxy diphenyl diselenide, 4',4-dichloro diphenyl diselenide and 2',2,4',4,6',6-hexamethyl diphenyl diselenide). These effects may be linked to the pro-oxidant activity exhibited by selenium compounds when used in relatively high concentrations.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 06/2009; 676(1-2):21-6. DOI:10.1016/j.mrgentox.2009.03.006 · 4.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A set of chiral β-seleno amines were prepared by the ring-opening reaction of unprotected aziridines. Under acid conditions diaryl or dialkyl diselenides were reduced by zinc and treated with unprotected aziridines to produce the desired products in good yields. Chiral β-telluro amine was also obtained using this method.