Diselenides and Benzisoselenazolones as Antiproliferative Agents and Glutathione-S-Transferase Inhibitors

Krasowska, Dorota; Iraci, Nunzio; Santi, Claudio; Drabowicz, J.; Cieślak, Marcin; Kaźmierczak-Barańska, Julia; Palomba, Martina; Królewska-Golińska, Karolina; Magiera, Jakub; Sancineto, Luca

doi:10.3390/molecules24162914

Cited by 38 publications

(31 citation statements)

References 68 publications

(80 reference statements)

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“…However, the study was interrupted before planned, because the data, contrary to the expectation, have not indicated potential beneficial effects of selenium or vitamin E. Despite the negative outcomes of SELECT (Dunn et al 2010 ; Klein et al 2011 ; Lippman et al 2009 ; Nicastro and Dunn 2013 ), the potential use of selenium in cancer prevention or treatment is still a matter of debate (Chapelle et al 2020 ; Vinceti et al 2018 ). Several experimental studies have indicated the potential anti-cancer properties of inorganic and organic forms of selenium (Álvarez-Pérez et al 2018 ; Gandin et al 2018 ; Gopalakrishna et al 2018 ; Krasowska et al 2019 ; Ruberte et al 2019 ; Sanmartín et al 2012 ; Sharma and Amin 2013 ; Spengler et al 2019 ; Steinbrenner et al 2013 ; Tan et al 2019 ). Some clinical studies have also demonstrated that selenite can have beneficial effects by itself or decrease some toxic effects of radiotherapy in cancer patients (Brodin et al 2015 ; Han et al 2019 ; Handa et al 2020 ; Knox et al 2019 ; Muecke et al 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Toxicology and pharmacology of synthetic organoselenium compounds: an update

2021

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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.

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Section: Introductionmentioning

confidence: 99%

Toxicology and pharmacology of synthetic organoselenium compounds: an update

2021

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“…Organoselenium compounds are gaining interest in the medicinal chemistry community due to their promising biological activities for a wide range of clinical applications [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. Starting from Ebselen, the first compound showing the ability to function as glutathione peroxidase (GPx) mimetic [ 8 ], several Se-bearing molecules were reported as anticancer [ 9 , 10 , 11 , 12 ], anti-inflammatory [ 13 , 14 ], antidepressant [ 15 , 16 ], and antibacterial [ 17 , 18 , 19 ], among others. Worth mentioning, some of us developed the DiSeBAs class of compounds [ 20 ], endowed with a potent anti-HIV activity due to their ability to inhibit the key viral protein NCp7 [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Sweet Selenium: Synthesis and Properties of Selenium-Containing Sugars and Derivatives

et al. 2020

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In the last decades, organoselenium compounds gained interest due to their important biological features. However, the lack of solubility, which characterizes most of them, makes their actual clinical exploitability a hard to reach goal. Selenosugars, with their intrinsic polarity, do not suffer from this issue and as a result, they can be conceived as a useful alternative. The aim of this review is to provide basic knowledge of the synthetic aspects of selenosugars, selenonium salts, selenoglycosides, and selenonucleotides. Their biological properties will be briefly detailed. Of course, it will not be a comprehensive dissertation but an analysis of what the authors think is the cream of the crop of this interesting research topic.

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“…Furthermore, a growing number of selenium-containing small molecules has been recently demonstrated to possess an array of biological properties, including antioxidant, [23][24][25] anticancer, 26 and enzyme modulator activities. [27][28][29][30][31] The development of novel routes towards organoselenium derivatives is, therefore, highly desirable. 16,32 In this scenario, we recently reported new synthetic procedures for the synthesis of selenium-containing functionalized small molecules under mild conditions.…”

confidence: 99%