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

Abstract

The ability of organoselenium molecules to mimic the activity of the antioxidant selenoenzyme glutathione peroxidase (GPx) allows for their use as antioxidant or prooxidant modulators in several diseases associated with the disruption of the cell redox homeostasis. Current drug design in the field is partially based on specific modifications of the known Se-therapeutics aimed at achieving more selective bioactivity towards particular drug targets, accompanied by low toxicity as the therapeutic window for organoselenium compounds tends to be very narrow. Herein, we present a new group of Se-based antioxidants, structurally derived from the well-known group of GPx mimics—benzisoselenazol-3(2H)-ones. A series of N-substituted unsymmetrical phenylselenides with an o-amido function has been obtained by a newly developed procedure: a copper-catalyzed nucleophilic substitution by a Se-reagent formed in situ from diphenyl diselenide and sodium borohydride. All derivatives were tested as antioxidants and anticancer agents towards breast (MCF-7) and leukemia (HL-60) cancer cell lines. The highest H2O2-scavenging potential was observed for N-(3-methylbutyl)-2-(phenylselanyl)benzamide. The best antiproliferative activity was found for (−)-N-(1S,2R,4R)-menthyl-2-(phenylselanyl)benzamide (HL-60) and ((−)-N-(1S,2R,3S,6R)-(2-caranyl))benzamide (MCF-7). The structure–activity correlations, including the differences in reactivity of the obtained phenyl selenides and corresponding benzisoselenazol-3(2H)-ones, were performed.

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

“…More recently, an another study relate to Ebselen derivatives was carried out by Scianowski and co‐workers [145] . In this work, the authors have prepared Ebselen derivatives to evaluate the GPx‐like activity as well as to improve the antioxidant profile.…”

“…More recently, an another study relate to Ebselen derivatives was carried out by Scianowski and co-workers. [145] In this work, the authors have prepared Ebselen derivatives to evaluate the GPx-like activity as well as to improve the antioxidant profile. The derivatization was based on the exchange of SeÀ N for SeÀ C ar bond, and obtaining a large substrate scope by the introduction of distinct structural moieties attached to the nitrogen atom.…”

Analytical Problems in Separation of Selenomethionine and Its Oxidative Product in HILIC HPLC

“…To our best knowledge, there are no reports regarding the exact mechanism of the reaction between the oxidized form of SeMet and DTT or βME, as well as its kinetic. The conversion of DTT to disulphide, its oxidized form, was observed [ 43 ], while Chéry et al postulated that dithiothreitol can degrade the original amino acids into DTT-Se molecules, probably a cyclic, with the consequent loss of the speciation information [ 44 ]. The formed SeMetO (as two diastereomers) can readily undergo facile racemization in aqueous media, mostly via the formation of achiral hydrates [ 23 ].…”

Selenium-Catalyzed Reduction of Hydroperoxides in Chemistry and Biology

“…The presence of selenium in enzymes involved in the endogenous enzymatic defense against harmful oxidants soon prompted for the design and synthesis of bioinspired molecules with antioxidant potential, i.e., capable of efficiently reduce peroxides [68][69][70]. Particularly, in the last fifty years, numerous compounds mimicking GPx activity have been prepared and tested in vitro and in vivo [71]. From a chemical point of view, they can be grouped into three classes, i.e., diaryldiselenides, selenenylamides and alkylselenides [72].…”