PHARMACOKINETIC STUDIES OF NEW SILVER-BASED COMPLEX

Objective: Investigation of pharmacokinetics parameters of the new silver-based compound of general formula C6H19Ag2N4LiO6S2, called Argosilâ€, with high antiviral activity.Methods: Water solution of complex administered intragastrically in the dose rate of 100 mg/kg body weight of mice BALB/c (males) aged 1.5-2.0 mo. Blood and tissues samples analyzed by mass spectrometry.Results: Half-life of the drug was about 4 h at the initial stage. About 5% of the initially introduced silver detected after 24 h. Maximum drug concentration observed in the lung tissues.Conclusion: Results make the basis for further test and clinical implementation. Taken into account low toxicity and antiviral properties of this compound, it looks especially effective for lung infections treatment.Â

Water Purification with Natural Sorbents: Effect of Surface Modification with Nano-structured Particles

Modified nanostructured sorbents are widely used in water treatment processes. In this work, aluminum and iron particles prepared by electro-spark dispersion have been applied as modifiers. Zeolite samples from "Holinskoe" mineral deposit (Russia, Republic of Buryatia), with a size smaller than 0.1 mm, have been modified with aluminum and iron particles, using a sol-gel process. The properties of the modified materials have been determined by means of sorption test, when removing ions Pb{2+}, Fe{3+} and Cd{2+} from the model solutions in static conditions. Using the method of thermal desorption of nitrogen (BET) it has been shown that increasing the iron content in the samples of nanostructured modified sorbents does not affect the increase in specific surface area and pore volume of the samples. Ions concentrations have been analyzed by stripping voltammetry and photocolorimetry. As a result, modified sorbents revealed a high efficiency sorption of heavy metals

In vitro effects of a novel silver-based complex on influenza virus

Objective: To study the mechanism of antiviral activity of a new silver-based compound of general formula C6H19Ag2N4 LiO6S2 on influenza virus. Materials and Methods: Antiviral properties were investigated on test culture of Madin–Darby canine kidney (MDCK) cells with serial tenfold dilutions of the influenza virus. The completeness of viral inactivation was confirmed by determining the virus titer after a double passage of virus-containing suspension in MDCK cell culture. Reverse transcription polymerase chain reaction analysis of viral RNA, enzyme immunoassay, and transmission electron microscopy for morphological analysis of influenza virus particles were applied for analysis of viral RNA and effect of substance influence. Results: The results indicate a significant change in the antigenic structure of viral proteins of influenza virus by the silver-containing complex. The main inactivation mechanism of influenza virus by the action of the silver-containing complex is associated primarily with the effect on virion protein structure rather than cleavage of the viral RNA. It was revealed that the mechanism for the inactivation of influenza virus is not associated with cleavage of viral RNA corresponding genes M, NS, or nucleoprotein but more probable with changes of the antigen determinants of virion. It was found a significant damaging effect on influenza virus under action of tested substance at concentration higher than 0.4 mM. Conclusion: The novel silver-based complex possesses antiviral properties and could be considered as a prospective antiviral drug

New Synthetic Approaches to Multifunctional Phenazinium Salt Derivatives

Two different approaches are offered for the synthesis under mild conditions of disubstituted phenazinium and benzo[a]phenazinium salts. Direct nucleophilic substitutions by primary and secondary amines in quaternary phenazinium salts containing an additional positive charge in the aliphatic part of the molecule were carried out. The substitution proceeds successively in positions 2 and 7, which allows selective introduction of different substituents into the heterocycle. Direct nucleophilic substitution in quaternary 2-N-alkyl-acetamidophenazinium and 5-alkoxy-benzo[a]phenazinium salts with different amines can also serve as a convenient method for the introduction of two different substituents

Investigation of DNA-damage and Chromosomal Aberrations in Blood Cells under the Influence of New Silver-based Antiviral Complex

Purpose: The problem of infectious diseases and drug resistance is becoming increasingly important worldwide. Silver is extensively used as an anti-infective agent, but it has significant toxic side effects. In this regard, it is topical to develop new silver compounds with high biological activity and low toxicity. This work is aimed to study DNA damage and chromosomal aberrations in blood cells under the influence of new silver-based compound of general formula C6H19Ag2N4LiO6S2, with antiviral activity. Methods: The comet assay was applied for the genotoxic affects assessment on mice blood leukocytes. DNA damage was determined bases on the percentage of DNA in a comet tail (tail DNA), under the influence of silver complex in different concentrations. Genotoxic effect of the tested substance on the somatic cells was determined by chromosomal aberration test of bone marrow cells of mice. Results: In the course of the experiments, no essential changes in the level of DNA damage in the cells were found, even at highest concentrations. The administration of the substance in doses up to 2.5 g/kg in mice did not cause any increase in the frequency of chromosomal aberration in bone marrow cells. Conclusion: Taking into account known silver drug genotoxic properties, the use of a given complexed silver compound has possible great advantages for potential applications in the treatment of infectious diseases

New Synthetic Approaches to Multifunctional Phenazinium Salt Derivatives

Abstract: Two different approaches are offered for the synthesis under mild conditions of disubstituted phenazinium and benzo[a]phenazinium salts. Direct nucleophilic substitutions by primary and secondary amines in quaternary phenazinium salts containing an additional positive charge in the aliphatic part of the molecule were carried out. The substitution proceeds successively in positions 2 and 7, which allows selective introduction of different substituents into the heterocycle. Direct nucleophilic substitution in quaternary 2-N-alkyl-acetamidophenazinium and 5-alkoxy-benzo[a]phenazinium salts with different amines can also serve as a convenient method for the introduction of two different substituents

Novel oligonucleotide analogues based on morpholino nucleoside subunits – Antisense technologies: New chemical possibilities

1721-1726 Even several decades after pioneer publications there is continued interest in the construction and synthesis of a variety of novel oligonucleotide analogues. The first oligonucleotide analogues which had a regular, predetermined structure containing nucleoside units joined with carbonate, carbamate, hydroxyacetate and hydroxyacetamide tethers have been developed in the 1970s. Further progress in oligonucleotide synthetic methods during the 1980s stimulated the development of a variety of oligonucleotide analogues containing modified carbohydrate and phosphate backbones. Particular attention has been given to the PNA (peptide nucleic acids), morpholino, and negatively charged PNA oligonucleotide analogues, which showed the most promise in a number of biological applications, such as diagnostics, nucleic acid analyses, and gene expression. The cost of parent compounds and oligonucleotide analogue synthesis is one of the most limiting factors to broad application. Studies that succeed in resolving this cost problem in the most effective way would be beneficial. Herein is presented a short review on oligonucleotide analogues that can be synthesized from inexpensive parent compounds — ribonucleosides — with or without the protection of heterocyclic bases, and with minimal protection of other reactive functions. </smarttagtype

Synthesis of nucleotide–amino acid conjugates designed for photo-CIDNP experiments by a phosphotriester approach

Conjugates of 2’-deoxyguanosine, L-tryptophan and benzophenone designed to study pathways of fast radical reactions by the photo Chemically Induced Dynamic Nuclear Polarization (photo-CIDNP) method were obtained by the phosphotriester block liquid phase synthesis. The phosphotriester approach to the oligonucleotide synthesis was shown to be a versatile and economic strategy for preparing the required amount of high quality samples of nucleotide–amino acid conjugates