Though the classical paper of Schwartz and Foltz did not establish dietary essentiality to selenium in rats, it gave the first demonstration that selenium could mitigate the deficiency of an essential vitamin (Schwarz and Foltz 1957). The importance of selenium to mammals started to be defined in 1957 when Schwartz and Foltz demonstrated that selenite and selenate could prevent liver necrosis caused by feeding a vitamin E-deficient diet to rats. In short, the early history of the element selenium in biology has been marked by the contrast between its toxic and beneficial effects. In addition, the toxicity of selenium became notorious in farm and experimental animals exposed to high levels of the element (Levine 1915, 1925 Painter 1941 Smith 1941). Subsequently, selenium was rarely used in cancer treatment in humans, possibly because its effectiveness in clinical studies was inconsistent (Weil 1915). In sharp contrast, the lethal effect of a single injection of selenite in one human patient with cancer can also be found in the literature, cited in Weil ( 1915). One of the first therapeutic uses of selenium was in the treatment of cancer and reports about the beneficial effects of elemental selenium in the treatment of inoperable carcinoma can be found in clinical studies published at the beginning of the twentieth century (Freeman 1922 Watson-Williams 1919 Weil 1915). Soon after its isolation by Jacobs Berzelius, in 1817, selenium was used in organic synthesis and investigated as a potentially toxic or beneficial agent both in animals (including humans) and plants (Levine 1915, 1925 Martin 1936 Rocha et al. Since its discovery about 200 years ago, selenium has been attracting the interest of chemists and biologists. The development of computational techniques that could predict rational modifications in the structure of organoselenium compounds to increase their specificity is required to construct a library of thiol-modifying agents with selectivity toward specific target proteins.įull size image A brief history of selenium: an element with two faces In summary, the outcomes of the clinical trials of ebselen as a mimetic of lithium or as an inhibitor of SARS-CoV-2 proteases will be important to the field of organoselenium synthesis. The thiol-oxidizing properties of organoselenium compounds are considered the molecular basis of their chronic toxicity however, the acute use of organoselenium compounds as inhibitors of specific thiol-containing enzymes can be of therapeutic significance.
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However, contrary to our early expectations that they could imitate selenoproteins, organoselenium compounds seem to have non-specific modulatory activation of antioxidant pathways and specific inhibitory effects in some thiol-containing proteins. In short, our knowledge about the pharmacological properties of simple organoselenium compounds is still elusive.
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However, they have similar anti-inflammatory and antioxidant activities, possibly, via activation of transcription factors, regulating the expression of antioxidant genes. Although ebselen and diselenides have some overlapping pharmacological properties, their molecular targets are not identical. The rediscovery of ebselen and its investigation in clinical trials have motivated the search for new organoselenium molecules with pharmacological properties. The use of selenium as a tool in organic synthesis and as a pharmacological agent goes back to the middle of the nineteenth and the beginning of the twentieth centuries.
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Here, we addressed the pharmacology and toxicology of synthetic organoselenium compounds and some naturally occurring organoselenium amino acids.