Toxicology and pharmacology of synthetic organoselenium compounds: an update

Abstract

Here, we addressed the pharmacology and toxicology of synthetic organoselenium compounds and some naturally occurring organoselenium amino acids. 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. The rediscovery of ebselen and its investigation in clinical trials have motivated the search for new organoselenium molecules with pharmacological properties. Although ebselen and diselenides have some overlapping pharmacological properties, their molecular targets are not identical. However, they have similar anti-inflammatory and antioxidant activities, possibly, via activation of transcription factors, regulating the expression of antioxidant genes. In short, our knowledge about the pharmacological properties of simple organoselenium compounds is still elusive. 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. 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. 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 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.

Ebselen and Analogues: Pharmacological Properties and Synthetic Strategies for Their Preparation

“…Among the whole class of selenorganic compounds [ 112 , 113 ], the most promising derivative in the anticancer research field is ethaselen (compound 27 , Figure 3 ), which is under clinical evaluation in TR, overexpressing non-small cell lung cancers [ 114 ]. Ebselen and ebsulfur are also proven to interfere with TR [ 115 ] and in 2018 their scaffolds were used as a template for the synthesis of novel TR inhibitors.…”

In Silico Prediction of Steroids and Triterpenoids as Potential Regulators of Lipid Metabolism

“…There are also many excellent reviews in the literature, which are devoted to the biological role and functions of organoselenium compounds [301][302][303][304]. Apparently, selena steroids are the main group of the essential metalloids that have been synthesized over the past 50 years, and approximately 300 have been synthesized [304][305][306][307][308][309].…”

Pharmacological properties of selenium and its preparations: from antioxidant to neuroprotector

“…The attention was paid again to ebselen, and then diselenides appeared, which are united by similar antioxidant and anti-inflammatory properties. It is assumed that these properties are realized due to the activation of transcription factors that regulate the expression of antioxidant genes (Nogueira et al 2021).…”