New Chiral Ebselen Analogues with Antioxidant and Cytotoxic Potential

Pacuła, Agata J.; Kaczor, Katarzyna B.; Antosiewicz, Jędrzej; Janecka, Anna; Długosz, Angelika; Janecki, Tomasz; Wojtczak, Andrzej; Ścianowski, Jacek

doi:10.3390/molecules22030492

Cited by 46 publications

(35 citation statements)

References 46 publications

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“…In case of N-propyl benzisoselenazolthione 7b and benzisoselenazolone 6b the presence of sulfur atom instead of oxygen significantly increased the antioxidant potential. Interestingly, the high activity of compound 7e fits to our previously observed trend that derivatives possessing a 3-methylbuthyl carbon chain in their structure, like N-3-methylbuthylbenzisoselenazolone 6e [22] and N-leucine methyl ester derivative 8 [28], exhibit significantly better antioxidant potential than ebselen (Figure 1). It can be concluded, that the presence of N-propyl and 3-methylbuthyl carbon chain in the structure of N-alkyl benzisoselenazolones and benzisoselenazolthiones improves the peroxide scavenging properties.…”

Section: Catalytical and Biological Activity Evaluationsupporting

confidence: 85%

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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Section: Catalytical and Biological Activity Evaluationsupporting

confidence: 85%

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

et al. 2018

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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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“…First, a series of benzisoselenazolones 1, 9-14 was prepared by two procedures, from 2,2-diselenobis(benzoic acid) (method A) 39 and by our method B, [42][43][44] involving the treatment of N-substituted o-iodobenzamide with dilithium diselenide, providing significantly better yields (Scheme 3).…”

Section: Resultsmentioning

confidence: 99%

Water-dependent synthesis of biologically active diaryl diselenides

Pacuła¹,

Obieziurska²,

Ścianowski³

et al. 2018

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A new one-step method for the synthesis of diaryl diselenides has been developed. The reaction of oiodobenzamides with dilithium diselenide can be controlled by the presence of water providing a simple and efficient protocol to obtain benzisoselenazolones or diaryl diselenides. A series of N-aryl ebselen derivatives and the corresponding diselenides was obtained. All synthesized compounds were tested in vitro as antioxidants and cytotoxic agents. N- (2,3,4-trimethoxyphenyl)benzisoselenazol-3(2H)-one was the best in vitro antioxidant and the corresponding diselenide the most potent cytotoxic agent against prostate cancer cell line DU145, being inactive towards healthy prostate cell line PNT1A.

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New Chiral Ebselen Analogues with Antioxidant and Cytotoxic Potential

Cited by 46 publications

References 46 publications

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

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

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

Water-dependent synthesis of biologically active diaryl diselenides

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