Synthesis of Novel Selenocyanates and Evaluation of Their Effect in Cultured Mouse Neurons Submitted to Oxidative Stress

Abstract

<p>Herein we report the synthesis of novel selenocyanates and assessment of their effect on the oxidative challenge elicited by hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) in cultured mouse neurons. First, <i>α</i>-methylene-<i>β</i>-hydroxy esters were prepared as precursors of allylic bromides. A reaction involving the generated bromides and sodium selenocyanate was conducted to produce the desired selenocyanates (<b>3a-f</b>). We next prepared cultures of neurons from 7-day-old-mice (<i>n </i>= 36). H<sub>2</sub>O<sub>2</sub> (10<sup>⁻5</sup> M) was added into the culture flasks as an oxidative stress inducer, alone or combined with one of each designed compounds. PhSe)<sub>2</sub> was used as positive control. It was carried out assessment of lipid (thiobarbituric acid reactive species, 4-hydroxy-2’-nonenal, 8-isoprostane), DNA (8-hydroxy-2’-deoxyguanosine) and protein (carbonyl) modification parameters. Finally, catalase and superoxide dismutase activities were also evaluated. Among the compounds, <b>3b</b>, <b>3d</b> and <b>3f</b> exhibited the most pronounced pattern of antioxidant activity, similar to (PhSe)<sub>2</sub>. These novel aromatic selenocyanates could be promising to be tried in most sophisticated <i>in vitro </i>studies or even at preclinical level.</p>

Benzimidazole- and Imidazole-Fused Selenazolium and Selenazinium Selenocyanates: Ionic Organoselenium Compounds with Efficient Peroxide Scavenging Activities

“…In 2020, Frizon et al reported a series of allylic selenocyanates, such as compounds 14−16, and evaluated for their antioxidant activities in cultured mouse neurons under oxidative stress induced by H 2 O 2 . 20 Interestingly, compounds 14−16 exhibited significant antioxidant activities comparable to that of diphenyl diselenide (Ph 2 Se 2 ). While a significant number of neutral antioxidant organoselenium compounds are reported in the literature as synthetic mimics of GPx, examples of ionic organoselenium compounds as antioxidants are relatively limited.…”

“…23 In 2014, Stoyanovsky et al reported the synthesis of cationic ebselen derivative 19 as a mitochondria-targeting GPx mimic with potential as a radiation mitigator. 24 In 2020, Arsenyan and coworkers have reported another ionic mitochondria-targeting fused isoselenazolium chloride (20), which exhibited potent anticancer activities toward breast cancer cells via elevation of the intracellular ROS level. 25 Herein, we report the first examples of benzimidazole-and imidazole-based ionic organoselenium compounds such as benzimidazole-and imidazolebased selenazolium selenocyanates (21a, 21b, 22a, and 22b), selenazinium selenocyanates (21c, 21d, 22c, and 22d) and the corresponding open-chain selenocyanates (21e, 21f, 22e, and 22f) as GPx mimics (Figure 2).…”

Flavonoid Derivatives as New Potent Inhibitors of Cysteine Proteases: An Important Step toward the Design of New Compounds for the Treatment of Leishmaniasis

“…These methodologies generally require high-cost equipment, result in low yield, and use toxic solvents, which reduces the sustainability of the process. In line with our interest in discovering and developing a new sustainable, efficient methodologies for biologically active compounds and patient-compliant alternative for leishmaniasis treatment [10][11][12][13][14][15][16][17], our research group aimed to yield natural-based bioactive compounds with multitarget properties. To achieve this purpose, we designed a scalable, easy-to-replicate, and inexpensive synthetic route to obtain flavonol and chalcone analogs.…”

Antimicrobial and Antibiofilm Activities of 4,5-Dihydro-1H-pyrazole-1-carboximidamide Hydrochloride against Salmonella spp.

“…As part of our research interest in synthesis and biological evaluation of heterocyclic compounds [19][20][21][22][23][24][25][26][27][28], herein we report the antimicrobial and antibiofilm activities, of two 4,5-dihydro-1H-pyrazole-1-carboximidamide hydrochlorides ((trifluoromethyl) phenyl-substituted and bromophenyl-substituted), against four pathogenic Salmonella spp. serotypes.…”