Vinylic telluride derivatives as promising pharmacological compounds with low toxicity

Abstract

The aim of the present study was to evaluate pharmacological and toxicological properties of (Z)-2-(methylthio)-1-(butyltelluro)-1-phenylethene 1a, (Z)-1-(4-methylphenylsulfonyl)-2-(phenyltelluro)-2-phenylethene 1b, (Z)-2-(butyltelluro)-1-(benzylthio)-1-heptene 1c and (Z)-2-(phenylthio)-1-(butyltelluro)-1-phenylethene 1d. In vitro, vinylic telluride derivatives 1a, 1d and 1c were more effective in reducing lipid peroxidation than compound 1b. The maximal inhibitory effect of vinylic telluride derivatives on lipid peroxidation was in the following order: 1a = 1d > 1c > 1b. Compound 1b was more potent in inhibiting delta-ALA-D activity (delta-aminolevulinate dehydratase) than compounds 1c and 1d. Based on the in vitro properties presented by compounds 1a (an antioxidant) and 1b (a pro-oxidant), toxicological parameters were assessed in vivo and ex vivo in rats. Calculated LD50 of compounds 1a and 1b, administered by oral route, were 20.5 and 1.44 micromol kg(-1), respectively. Compound 1b induced behavioral alterations in the open field test. Renal and spleenic delta-ALA-D activities were inhibited in rats treated orally with compound 1a. Compound 1b stimulated delta-ALA-D activity in liver and spleen of rats. Rats treated with compound 1b had increased hepatic, renal and spleenic lipid peroxidation. Renal and hepatic markers were not altered when compounds 1a and 1b were administered to rats at doses of around LD50, while compound 1a at high doses changed aspartate aminotransferase activity and urea levels. Based on in vitro results, this study demonstrated that compounds 1a and 1d are promising antioxidant compounds. Ex vivo data reinforce compound 1a as a promising drug for more detailed pharmacological studies.

A Possible Neuroprotective Action of a Vinylic Telluride against Mn-Induced Neurotoxicity

“…Nevertheless, these compounds can also be extremely toxic following in vivo exposure (Laden and Porter, 2001;Nogueira et al, 2004). It appears that the nature of the organic moiety can considerably influence the toxicity of organotellurides in rodents (Borges et al, 2008;Savegnago et al, 2006). Nevertheless, diethyl-2-phenyl-2-tellurophenyl vinylphosphonate (DPTVP) is a vinyl telluride compound with very low toxicity (LD 50 to mice > 500 lmol/kg and to rats~4 lmol/kg), as well no neurotoxic effects, as it does not alter oxidant/prooxidant balance, mitochondrial viability nor behavior.…”

Hippocampal acetylcholinesterase activation induced by streptozotocin in mice is protected by an organotellurium compound without evidence of toxicity

“…These results corroborate Rosa et al (2017), who evaluated 3j toxicity when given as a single 43.10 mg/kg dose to mice. Thus, our results suggest that this chemical compound does not have pronounced toxicity and may be investigated to pharmacological purposes in the treatment of symptoms and signals of other pathologies where other telluric compounds are effective (Jacob et al 2000, Zeni et al 2001a, b, Ávila et al 2008, 2011, Borges et al 2008, Okoronkwo et al 2009. Additionally, 3j could be administered in a daily dose higher than 8.62 mg/kg/day or time interval longer than 25 days in one 8.62 mg/kg/day dose, since, as demonstrated in our results, higher doses and more extended periods are not harmful to young adult mice.…”

“…The synthesis of inorganic and organic compounds containing tellurium, such as tellurols, tellurides, telluranes, and tellurates, is the subject of several scientific investigations (Cunha et al 2009, Irfan et al 2020. Immunomodulatory (Cunha et al 2009), antioxidant (Jacob et al 2000, Nogueira et al 2004, Ávila et al 2008, Borges et al 2008, Cunha et al 2009, Rosa et al 2017), antitumoral (Nogueira et al 2004, Rosa et al 2017), antibacterial (Al-Masoudi et al 2015, anti-inflammatory (Zeni et al 2001a, b), antifungal (Al-Masoudi et al 2015), antihelmintic (Cunha et al 2009), antidepressant (Okoronkwo et al 2009), and hepatoprotective (Ávila et al 2011 properties have been reported. Advances in synthesis of these compounds encourage the development of studies of promising agents in therapy of diseases (Nogueira et al 2004, Irfan et al 2020.…”

Synthesis, characterization and antioxidant activity of organoselenium and organotellurium compound derivatives of chrysin

“…The results obtained in the DPPH assay are in agreement with several reports in the literature, in which tellurium-containing compounds have shown to be very effective antioxidant agents, even more than their selenium analogues. [26][27][28][33][34][35] Although Sim and co-workers 36 have demonstrated that chrysin 1 presents low antioxidant activity in the DPPH assay, (6.4% and 8.5% inhibitory effect, at 100 and 1000 mM, respectively), in our hands, chrysin did not present any significant activity in all the assays performed (data not shown).…”