Antioxidant properties of diorganoyl diselenides and ditellurides: modulation by organic aryl or naphthyl moiety

Abstract

Diorganoyl dichalcogenide compouds can have antioxidant activity in different in vitro and in vivo models. Here, we have compared the potential antioxidant activity of 1-dinaphthyl diselenide (1-NapSe)(2), 2-dinaphthyl diselenide (2-NapSe)(2), 1-dinaphthyl distelluride (1-NapTe)(2), 2-dinaphthyl ditelluride (2-NapTe)(2) with their well-studied analogs diphenyl diselenide ((PhSe)(2)) and diphenyl telluride ((PhTe)(2)). (PhSe)(2), (PhTe)(2), and naphthalene analogs-inhibited Fe(II)-induced lipid peroxidation, catalytically decomposed hydrogen peroxide and oxidized thiols, such as dithiothreitol (DTT), Cysteine (CYS), dimercaptopropionic acid (DMPS), and thiophenol (PhSH). (PhSe)(2) was the less potent of the tested compounds against Fe(II)-induced lipid peroxidation in brain homogenates and the change in the organic moiety from an aryl to naphthyl group increased considerably the antioxidant potency of diselenide compounds. However, the change from aryl to naphthyl had little effect on the thio-peroxidase-like activity of diorganoyl dichalcogenides. These results suggest that minor changes in the organic moiety of aromatic diselenide compounds can modify profoundly their capacity to inhibit iron-induced lipid peroxidation. The pharmacological properties of organochalcogens are thought to be linked to their capacity of modulating oxidative stress. Consequently, it becomes important to explore the toxicological properties of dinaphthyl diselenides and ditellurides.

Role of the Chalcogen (S, Se, Te) in the Oxidation Mechanism of the Glutathione Peroxidase Active Site

“…This is in agreement with the promising results obtained on the antioxidant efficiency of organotellurides, which have paved the route for their use as drugs . In fact, their toxicity seems to be comparable to that of organoselenides, which have been studied for a few decades and represent the paradigmatic GPx mimics. High peroxidase efficiency has also been reported for a cyclodextrin‐derived tellurium compound …”

General AMBER Force Field Parameters for Diphenyl Diselenides and Diphenyl Ditellurides

“…In addition, Te compounds have been investigated as chemopreventive agents and diphenylditelluride appears to have a very high capacity of inducing apoptotic cell death. 27,33 Importantly, the toxicity of organotellurides is found to be comparable to organoselenides and this paves the route to their possible use as drugs, in particular as antioxidant GPx mimics, although careful control is warmly recommended. 27,33 From a mechanistic point of view, small organoselenium compounds show some limitations and often their catalytic activity is relatively poor.…”

“…27,33 Importantly, the toxicity of organotellurides is found to be comparable to organoselenides and this paves the route to their possible use as drugs, in particular as antioxidant GPx mimics, although careful control is warmly recommended. 27,33 From a mechanistic point of view, small organoselenium compounds show some limitations and often their catalytic activity is relatively poor. 24 On the basis of the available experimental and computational studies this can be ascribed to (i) a competing undesired thiol exchange reaction which hampers the regeneration of the selenol, 34 due to the fact that nucleophilic attack at Se (reaction III, Scheme 1) is both thermodynamically and kinetically favored; 35,36 (ii) the nature of the thiol cosubstrate, which may have a dramatic effect on the catalytic activity of ebselen and its analogues; [37][38][39][40] (iii) the nonspecificity for the substrate which leads to undesirable reactions with Cys residues in different protein sites.…”

Organodiselenides: Organic Catalysis and Drug Design Learning from Glutathione Peroxidase

“…On the other hand, it has been demonstrated that diphenyl diselenide 1 may interfere with the synthesis of heme-containing proteins via ALA-D inhibition [60]. Braga, Rocha, Nogueira and co-workers have been studying exten- sively the applications of diphenyl diselenide and its derivatives in biochemistry, pharmacology and toxicology, with a particular focus on the synthetic aspects [12,15,35,37,38,50,[53][54][55]. In presence of hydroperoxides and thiols, nucleophilic attack of sulfur at a selenium center occurs first, promoting Se-Se bond cleavage [143].…”

“…Since few decades, much effort has been dedicated to the synthesis and reactivity properties of organochalcogenides as mimics of GPx for their potential anti-oxidant activity and possible use as drugs [12,13]. Organoselenides are undoubtedly the most studied, although also organotellurides have shown promising results in vitro as well as in vivo [12,[14][15][16]. From a biochemical point of view, the most remarkable differences between sulfur and selenium are the larger polarizability of Se and the lower pKa of SeH [11].…”