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

Abstract

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.

Selenium‐NMR Spectroscopy in Organic Synthesis: From Structural Characterization Toward New Investigations

“…Only one selenium compound was stable enough to carry out the analysis by NMR (Scheme 15). This instability of hypervalent selenium compounds was also observed by Helgueira and co‐workers [37] . The selenium heterocycles and complexes were characterized by single crystal X ‐ray diffraction.…”

“…This instability of hypervalent selenium compounds was also observed by Helgueira and coworkers. [37] The selenium heterocycles and complexes were characterized by single crystal X-ray diffraction.…”

“…In the second section, distinct forms to incorporate selenium moiety in organic substrates are described. The third section of this review brings the selenium‐catalyzed functionalization of small organic molecules, emphasizing the oxidized forms of selenium [36,37] . Finally, the fourth section discuss special cases to explore organoselenium compounds, including in emulsions, as ionic liquids, in metathesis reaction, and as chemical sensor.…”

Phenylselanyl Group Incorporation for “Glutathione Peroxidase-Like” Activity Modulation

“…Determination of the antioxidant and antiproliferative potential of all obtained molecules revealed a particular structure-activity relationship. Besides the observed influence of the N-substituent on their biological potential, it was also recently highlighted by Santi and co-workers [17], that the form of the Se-moiety is crucial for the specific catalytic activity of the designed GPx-mimics. To further differentiate the structures and to broaden the scope of the tested molecules, we introduced a phenylselanyl group as a new benzisoselenazolone core modification (7b-23b, Scheme 2).…”

Divers Transformations Leading to New Potent GPx Mimetics

“…The acids 16af were obtained using two alternative methods: by oxidation of N-alkylbenzisoselenazol-3(2H)-ones 4a-f (method C) or the corresponding diselenides 15a-f (method D) with 30% H2O2. Nalkylbenzeneseleninic acids 16a-f in the next step were converted into the corresponding benzeneseleninic salts 17a-f by reaction with potassium tert-butoxide in anhydrous ethanol (Scheme 4) [12]. Scheme 4.…”