Inhibition of peroxynitrite- and peroxidase-mediated protein tyrosine nitration by imidazole-based thiourea and selenourea derivatives

Abstract

In the present study, the synthesis and characterization of a series of N-methylimidazole-based thiourea and selenourea derivatives are described. The new compounds were also studied for their ability to inhibit peroxynitrite (PN)- and peroxidase-mediated nitration of protein tyrosine residues. It has been observed that the selenourea derivatives are more efficient than the thiourea-based compounds in the inhibition of protein nitration. The higher activity of selenoureas as compared to that of the corresponding thioureas can be ascribed to the zwitterionic nature of the selenourea moiety. Single crystal X-ray diffraction studies on some of the thiourea and selenourea derivatives reveal that the C=S bonds in thioureas possess more of double bond character than the C=Se bonds in the corresponding selenoureas. Therefore, the selenium compounds can react with PN or hydrogen peroxide much faster than their sulfur analogues. The reactions of thiourea and selenourea derivatives with PN or hydrogen peroxide produce the corresponding sulfinic or seleninic acid derivatives, which upon elimination of sulfurous/selenous acids produce the corresponding N-methylimdazole derivatives.

An Efficient Synthesis of 1,3-Dialkylimidazole-2-Selenones

“…1 based on that proposed for the reaction of 1,3-dialkylimidazolium salts and Se. [3][4][5][6] The formation of 1-butyl-3-methylimidazole-2-selenone (1b) may involve two-steps (see Fig. 1): (1) deprotonation of 1-butyl-3-methylimidazolidine chloride salt 1a by K 2 CO 3 to give the N-heterocyclic carbene intermediate C and (2) reaction of intermediate C with selenium to produce 1-butyl-3-methylimidazole-2-selenone 1b.…”

The Reactive Sulfur Species Concept: 15 Years On

“…Indeed, such a concept may be useful to cover: (a) newly identified natural selenium metabolites, such as selenoneine, a rather unusual natural selenium compound which has been found in the blood of tuna and seems to be highly reactive, (b) inorganic selenium species with biological relevance, such as naturally generated selenium nanoparticles found in many strains of Staphylococcus and other bacteria and used on occasion to fortify drinks with selenium, (c) selenium agents currently in development with potential pharmaceutical applications, such as organic seleninic acids, organic selenourea derivatives, selenazolinium salts, and (d) recently discovered selenoproteins and the various modifications of selenocysteine found already or to be expected in those proteins (such as selenosulfide, diselenide, seleninic acids, selenoxides, etc.) [126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142]. Whilst those RSeS at first sight may be less relevant to redox biology compared to RSS because of their number, variety and concentration in most cells and organisms, they are clearly on the rise in the field of food supplementation and pharmaceutical research.…”

Synthesis and Characterization of Sterically Congested Mesityltris(imidazolium) Salts and the Corresponding Highly Crystalline Tris-selone Derivatives

“…In fact, mono-and bis-imidazole selones have been extensively used to generate transitionmetal-based complexes [26][27][28][29][30][31][32][33][34][35][36][37][38] and have furtherb een employed in versatile catalytic applications, such as polymerization [39] and the reduction of nitrobenzenes. [40] Moreover,s uch selenoketones have been used as inhibitors of lactoperoxidase-catalyzed oxidation and tyrosine nitration, [41][42][43] as an analogue of the antithyroidd rug methimazole, [44][45][46] in optoelectronics, [47] as chemicals ensors, [48] and also as ac hemical tool for Pd II extraction from water. [49] Since the first report of the one-pot synthesis of as elone startingf rom an imidazolium salt and elemental seleniumb yJ in et al, [50] as ignificant number of reports has been published following as imilar synthetic protocol.…”