Genotoxicity of chromium (III) and cobalt (II) and interactions between them

Introduction. Chromium and cobalt are essential trace elements that are required only in a small amount, otherwise their excess can cause toxic effects. Aim. The aim of this study was to determine the effects of chromium (III) and cobalt (II) and their combinations on genotoxicity in human fibroblasts cells (BJ). Material and methods. In this work, comet and micronucleus assays were used. The BJ cells were exposed to chromium chloride and cobalt chloride at concentration ranges from 100 to 1400 µM. Mixtures of these elements were prepared so as to examine interactions between them. Results. The present study shows the genotoxic effects of chromium (III) and cobalt (II) and their mixtures on BJ cells. In the comet assay, no comets were observed at the lowest concentrations; in the higher, a significant increase in their percentage was observed. In the other assay (formation of micronuclei), a statistically significant increase in the number of cells with micronuclei was observed in the BJ cells spiked with cobalt chloride and chromium chloride. In the case of simultaneous incubation of chromium chloride at 200 µM and cobalt chloride at 1000 µM in the BJ line, antagonism was observed. However, the interaction of chromium chloride at the 1000 µM and cobalt chloride at 200 µM leads to synergism between the studied elements. Conclusions. Cobalt (II) and chromium (III) show genotoxic properties, they induce breaks in double and single-stranded DNA and they cause formation of AP-sites that do not have purine or pyrimidine bases.

N-Glycosylation with Sulfoxide Donors for the Synthesis of Peptidonucleosides

<p>We report here the synthesis of peptidonucleosides obtained after glycosylation of different pyrimidine bases with glucopyranosyl donors carrying an azide group at the C4 position. A methodological study involving different anomeric leaving groups (acetate, phenylsulfoxide and <i>ortho</i>-hexynylbenzoate) showed that a sulfoxide donor in combination with trimethylsilyl triflate as the promoter led to the best yields.</p>

N-Glycosylation with Sulfoxide Donors for the Synthesis of Peptidonucleosides

<p>We report here the synthesis of peptidonucleosides obtained after glycosylation of different pyrimidine bases with glucopyranosyl donors carrying an azide group at the C4 position. A methodological study involving different anomeric leaving groups (acetate, phenylsulfoxide and <i>ortho</i>-hexynylbenzoate) showed that a sulfoxide donor in combination with trimethylsilyl triflate as the promoter led to the best yields.</p>

N-Glycosylation with sulfoxide donors for the synthesis of peptidonucleosides

The activation of sulfoxide donors in the glycosylation of pyrimidine bases led efficiently to glycosylated adducts that were converted into peptidonucleosides, the analogues of gougerotin.

Anion exchange resins in phosphate form as versatile carriers for the reactions catalyzed by nucleoside phosphorylases

In the present work, we suggested anion exchange resins in the phosphate form as a source of phosphate, one of the substrates of the phosphorolysis of uridine, thymidine, and 1-(β-ᴅ-arabinofuranosyl)uracil (Ara-U) catalyzed by recombinant E. coli uridine (UP) and thymidine (TP) phosphorylases. α-ᴅ-Pentofuranose-1-phosphates (PF-1Pis) obtained by phosphorolysis were used in the enzymatic synthesis of nucleosides. It was found that phosphorolysis of uridine, thymidine, and Ara-U in the presence of Dowex® 1X8 (phosphate; Dowex-nPi) proceeded smoothly in the presence of magnesium cations in water at 20–50 °C for 54–96 h giving rise to quantitative formation of the corresponding pyrimidine bases and PF-1Pis. The resulting PF-1Pis can be used in three routes: (1) preparation of barium salts of PF-1Pis, (2) synthesis of nucleosides by reacting the crude PF-1Pi with an heterocyclic base, and (3) synthesis of nucleosides by reacting the ionically bound PF-1Pi to the resin with an heterocyclic base. These three approaches were tested in the synthesis of nelarabine, kinetin riboside, and cladribine with good to excellent yields (52–93%).

Synthesis and Antiviral Evaluation of 3′-Fluoro-5′-norcarbocyclic Nucleoside Phosphonates Bearing Uracil and Cytosine as Potential Antiviral Agents

Carbocyclic nucleoside analogues are an essential class of antiviral agents and are commonly used in the treatment of viral diseases (hepatitis B, AIDS). Recently, we reported the racemic synthesis and the anti-human immunodeficiency virus activities (HIV) of 3′-fluoro-5′-norcarbocyclic nucleoside phosphonates bearing purines as heterocyclic base. Based on these results, the corresponding racemic norcarbocyclic nucleoside phosphonates bearing pyrimidine bases were synthesized. The prepared compounds were evaluated against HIV, but none of them showed marked antiviral activity compared to their purine counterparts.