Water-dependent synthesis of biologically active diaryl diselenides

Pacuła, Agata J.; Obieziurska, Magdalena; Ścianowski, Jacek; Kaczor, Katarzyna B.; Antosiewicz, Jędrzej

doi:10.24820/ark.5550190.p010.311

Cited by 11 publications

(12 citation statements)

References 35 publications

(40 reference statements)

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“…The first step of this study involved the synthesis of N-alkyl benzeneselenenic acids with o-amido function. The compounds were obtained by two different methods based on the oxidation of N-alkylbenzisoselenazol-3(2H)-ones 8 -method A, or corresponding diselenides 9 -method B. Derivatives 8 and 9 were synthetized according to our previously published procedures [22][23][24][25]. The overall yields of both methods A and B were comparable.…”

Section: Resultsmentioning

confidence: 99%

Seleninic Acid Potassium Salts as Water-Soluble Biocatalysts with Enhanced Bioavailability

et al. 2020

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Organoselenium compounds are well-known glutathione peroxidase (GPx) mimetics that possess antioxidants/prooxidant properties and are able to modulate the concentration of reactive oxygen species (ROS), preventing oxidative stress in normal cells or inducing ROS formation in cancer cells leading to apoptosis. The purpose of this study was the synthesis of potent GPx mimics with antioxidant and anticancer activity along with improved bioavailability, as a result of good solubility in protic solvents. As a result of our research, glutathione peroxidase (GPx) mimetics in the form of water-soluble benzeneseleninic acid salts were obtained. The procedure was based on the synthesis of 2-(N-alkylcarboxyamido)benzeneselenenic acids, through the oxidation of benzisoselenazol-3(2H)-ones or analogous arenediselenides with an amido group, which were further converted to corresponding potassium salts by the treatment with potassium tert-butanolate. All derivatives were tested as potential antioxidants and anticancer agents. The areneseleninic acid salts were significantly better peroxide scavengers than analogous acids and the well-known organoselenium antioxidant ebselen. The highest activity was observed for the 2-(N-ethylcarboxyamido)benzeneselenenic acid potassium salt. The strongest cytotoxic effect against breast cancer (MCF-7) and human promyelocytic leukemia (HL-60) cell lines was found for 2-(N-cyclohexylcarboxyamido)benzeneselenenic acid potassium salt and the 2-(N-ethylcarboxyamido)benzeneselenenic acid, respectively. The structure–activity correlations, including the differences in reactivity of benzeneseleninic acids and corresponding salts were evaluated.

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Section: Resultsmentioning

confidence: 99%

Seleninic Acid Potassium Salts as Water-Soluble Biocatalysts with Enhanced Bioavailability

et al. 2020

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“…Compound 1-6 were synthesized according to literature procedure(1–3), as shown in Scheme S1. The chemical reagents and solvents are purchased from commercial sources, and used without further purification, unless stated otherwise.…”

Section: Methodsmentioning

confidence: 99%

High-throughput tandem-microwell assay for ammonia repositions FDA-Approved drugs to Helicobacter pylori infection

Liu

Zhang

et al. 2021

Preprint

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To date, little attempt has been made to develop new treatments for Helicobacter pylori (H. pylori), although the community is aware of the shortage of treatments for H. pylori. In this study, we developed a 192-tandem-microwell-based high-throughput-assay for ammonia that is a known virulence factor of H. pylori and a product of urease. We could identify few drugs, i.e. panobinostat, dacinostat, ebselen, captan and disulfiram, to potently inhibit the activity of ureases from bacterial or plant species. These inhibitors suppress the activity of urease via substrate-competitive or covalent-allosteric mechanism, but all except captan prevent the antibiotic-resistant H. pylori strain from infecting human gastric cells, with a more pronounced effect than acetohydroxamic acid, a well-known urease inhibitor and clinically used drug for the treatment of bacterial infection. This study offers several bases for the development of new treatments for urease-containing pathogens and to study the mechanism responsible for the regulation of urease activity.

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“…The first step included the synthesis of carbonyl substrates for the transformation of oxygenbased functional groups to their thio-analogues. Using our previously designed procedures we have obtained a series of N-alky-o-iodobenzamides 4a-f that were further transformed, by the reaction with dilithium diselenide, into corresponding N-alkylbenzisoselenazolones 6a-f [24,25] (Scheme 4). The first step included the synthesis of carbonyl substrates for the transformation of oxygen-based functional groups to their thio-analogues.…”

Section: Chemistrymentioning

confidence: 99%

“…The first step included the synthesis of carbonyl substrates for the transformation of oxygen-based functional groups to their thio-analogues. Using our previously designed procedures we have obtained a series of N-alky-o-iodobenzamides 4a-f that were further transformed, by the reaction with dilithium diselenide, into corresponding N-alkylbenzisoselenazolones 6a-f [24,25] The treatment of amides 4a-f with Lawessons's reagent (LR) carried out in standard conditions [26] (Method C) resulted in only moderate yields of the thioamides 5a-f. Performing the reaction with microwave irradiation in solvent-free conditions (Method D) enabled us to significantly reduce the reaction time (3 min) and obtain the final product in good yield (44-81%) ( Table 1).…”

Section: Chemistrymentioning

confidence: 99%

The Influence of O/S Exchange on the Biocatalytical Activity of Benzisoselenazol-3(2H)-ones

et al. 2018

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The crucial feature of organoselenium compounds, when considering them as promising drug candidates in cancer therapy, is their unique ability to alter the cellular redox regulations. Organic Se-molecules continue to demonstrate a positive therapeutic effect both in cancer prevention—as antioxidants, and treatment—as prooxidants. The growing interest in this field of research highlights the need to search for particular pharmacophore motifs, which could enhance the efficiency and selectivity, and decrease the toxicity of potential anticancer agents. Herein, a series of redox-active organoselenium derivatives—N-functionalized benzisoselenazol-3(2H)-thiones, has been designed and synthetized. A new synthetic pathway, with the application of Lawesson’s reagent, has been developed and efficiently applied. The key steps involving microwave irradiation facilitated performing the reaction in solvent-free conditions, shortening the reaction time and significantly improving the overall yield of the process. Six N-alkyl derivatives have been obtained and tested as antioxidant catalysts and anti-proliferative agents. The N-propyl benzisoselenazol-3(2H)-thione was the best peroxide scavenger and the N-cyclohexyl derivative exhibited the best cytotoxic activity towards prostate cancer cell line DU145.

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Water-dependent synthesis of biologically active diaryl diselenides

Cited by 11 publications

References 35 publications

Seleninic Acid Potassium Salts as Water-Soluble Biocatalysts with Enhanced Bioavailability

Seleninic Acid Potassium Salts as Water-Soluble Biocatalysts with Enhanced Bioavailability

High-throughput tandem-microwell assay for ammonia repositions FDA-Approved drugs to Helicobacter pylori infection

The Influence of O/S Exchange on the Biocatalytical Activity of Benzisoselenazol-3(2H)-ones

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