- Diselenides and benzisoselenazolones as antiproliferative agents and glutathione-S-transferase inhibitors
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A series of variously functionalized selenium-containing compounds were purposely synthesized and evaluated against a panel of cancer cell lines. Most of the compounds showed an interesting cytotoxicity profile with compound 5 showing a potent activity on MCF7 cells. The ethyl amino derivative 5 acts synergistically with cis-platin and inhibits the GST enzyme with a potency that well correlates with the cytotoxicity observed in MCF7 cells. A computational analysis suggests a possible binding mode on the GST enzyme. As the main outcome of the present study, the ethyl amino derivative 5 emerged as a valid lead compound for further, future developments.
- Krasowska, Dorota,Iraci, Nunzio,Santi, Claudio,Drabowicz, Józef,Cieslak, Marcin,Ka?mierczak-Barańska, Julia,Palomba, Martina,Królewska-Golińska, Karolina,Magiera, Jakub,Sancineto, Luca
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- Catalytic reduction of graphene oxide nanosheets by glutathione peroxidase mimetics reveals a new structural motif in graphene oxide
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A catalytic reduction of graphene oxide (GO) by glutathione peroxidase (GPx) mimics is reported. This study reveals that GO contains peroxide functionalities, in addition to the epoxy, hydroxyl and carboxylic acid groups that have been identified earlier. It also is shown that GO acts as a peroxide substrate in the GPx-like catalytic activity of organoselenium/tellurium compounds. The reaction of tellurol, generated from the corresponding ditelluride, reduces GO through the glutathione (GSH)-mediated cleavage of the peroxide linkage. The mechanism of GO reduction by the tellurol in the presence of GSH involves the formation of a tellurenic acid and tellurenyl sulfide intermediates. Interestingly, the GPx mimics also catalyze the decarboxylation of the carboxylic acid functionality in GO at ambient conditions. Whereas the selenium/tellurium-mediated catalytic reduction/decarboxylation of GO may find applications in bioremediation processes, this study suggests that the modification of GO by biologically relevant compounds such as redox proteins must be taken into account when using GO for biomedical applications because such modifications can alter the fundamental properties of GO.
- Vernekar, Amit A.,Mugesh, Govindasamy
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p. 16699 - 16706
(2014/01/06)
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- Tertiary amine-based glutathione peroxidase mimics: Some insights into the role of steric and electronic effects on antioxidant activity
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In this work, several tertiary amine-based diaryl diselenides were synthesized and evaluated for their glutathione peroxidase (GPx)-like antioxidant activities using hydrogen peroxide, tert-butyl hydroperoxide and cumene hydroperoxide as substrates and thiophenol (PhSH) and glutathione (GSH) as co-substrates. A comparison of the GPx-like activity of 4-methoxy-substituted N,N-dialkylbenzylamine-based diselenides with that of the corresponding 6-methoxy-substituted compounds indicates that the activity highly depends on the position of the methoxy substituent. Although the methoxy group at 4- and 6-position alters the electronic properties of selenium, the substitution at the 6-position provides the required steric protection for some of the key intermediates in the catalytic cycle. A detailed experimental and theoretical investigation reveals that the 6-methoxy substituent prevents the undesired thiol exchange reactions at the selenium centers in the selenenyl sulfide intermediates. The 6-methoxy substituent also prevents the formation of seleninic and selenonic acids. When PhSH is used as the thiol co-substrate, the 4-methoxy-substituted diselenides exhibit GPx-like activity similar to that of the parent compounds as the 4-methoxy substituent does not block the selenium center in the selenenyl sulfide intermediates from thiol exchange reactions. In contrast, the 4-methoxy substituent significantly enhances the GPx-like activity of the diselenides when glutathione (GSH) is used as the co-substrate.
- Bhowmick, Debasish,Mugesh, Govindasamy
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p. 10550 - 10560,11
(2012/12/13)
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- Synthesis and structure - activity correlation studies of secondary- and tertiary-amine-based glutathione peroxidase mimics
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In this study, a series of secondary- and tertiary-amino-substituted diaryl diselenides were synthesized and studied for their glutathione peroxidase (GPx) like antioxidant activities with H2O2, cumene hydroperoxide, or tBuOOH as sub
- Bhabak, Krishna P.,Mugesh, Govindasamy
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experimental part
p. 9846 - 9854
(2010/04/29)
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- First detection of a selenenyl fluoride ArSe-F by NMR spectroscopy: The nature of Ar2Se2/XeF2 and ArSe-SiMe 3/XeF2 reagents
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Arylselenenyl fluorides ArSeF are obtained from diselenides Ar 2Se2 or arylselenotrimethylsilanes ArSe-SiMe3, and XeF2. They are detected by low-temperature 19F and 77Se NMR spectroscopy. Substitution in the ortho position of the aromatic ring to provide electronic or steric protection is a requirement for their formation. ArSe-F compounds decompose according to 3 ArSe-F → [ArSe-SeF2Ar] + ArSe-F- → ArSeF3 + Ar 2Se2. Reaction energies for this disproportionation as well as that of the sulfur and tellurium homologues have been calculated with MP2, CCSD(T,) and B3 LYP methods. They were found to be increasingly exothermic in the sequence S 77Se and 19F chemical shifts have been calculated by GIAO-MP2 and GIAO-B3LYP methods and are in good agreement with experimental values.
- Poleschner, Helmut,Seppelt, Konrad
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p. 6565 - 6574
(2007/10/03)
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- Synthesis, characterisation and reactions of bis[2-(dimethylaminomethyl)-phenyl] diselenide: Its structure and that of [2-(dimethylaminomethyl)phenyl]-selenium bromide
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Bis[(2-dimethylaminomethyl)phenyl] diselenide (RSe)2 was obtained by the organolithium route. It underwent facile reaction with stoichiometric amounts of bromine and iodine to give the corresponding arylselenium halides RSeBr and novel RSeI in
- Kaur, Rupinder,Singh, Harkesh B.,Patel, Rajan P.
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p. 2719 - 2726
(2007/10/03)
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- Development of Synthetic Compounds with Glutathione Peroxidase Activity
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Glutathione peroxidase is the major defense in the lens of the eye against hydrogen peroxide.The damage caused by hydrogen peroxide has been implicated in the formation of cataract.Organoselenium compounds which show catalytic activity in the enzyme assay
- Wilson, Stephen R.,Zucker, Paul A.,Huang, Ruey-Ruey C.,Spector, Abraham
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p. 5936 - 5939
(2007/10/02)
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