Russian Journal of Bioorganic Chemistry

A novel series of 3-pyridinecarbonitrile derivatives incorporating sulfonamide moieties and sulfonyl derivatives was synthesized using 2-chloro-6-methylnicotinonitrile as a strategic starting material. The structures of the synthesized compounds were elucidated on the basis of elemental analysis, IR, 1H NMR, 13C NMR, and mass spectral data. All the prepared compounds were evaluated for their in vitro anticancer activity against breast cancer cell line (MCF-7). Most of the compounds showed good to moderate activity, higher than that of the reference drug doxorubicin. Two compounds showed the same activity as doxorubicin, while three compounds exhibited remarkable activity.

We have demonstrated that the water and ethanol extracts of the Nepeta cataria, Nepeta sibirica, Scutellaria baicalensis, Hyssopus officinalis, and Betonica officinalis plants, water extracts of Dracocephalum moldavica, Glechoma hederacea, Mentha arvensis, Prunella vulgaris, and Melissa officinalis, and ethanol extracts of Mentha piperita, Mentha crispa, Origanum vulgare, Hyssopus officinalis, and Salvia verticillata showed antiviral activity against the influenza virus subtype H5N1. The water extracts of Nepeta cataria and Glechoma hederacea showed the highest antiviral effect against the H5N1 subtype (NI 3.75). The water and ethanol extracts of Scutellaria baicalensis, Mentha piperita, Mentha arvensis, and Mentha crispa, water extract of Dracocephalum moldavica, and ethanol extracts of Glechoma hederacea, Origanum vulgare, Prunella vulgaris, Hyssopus officinalis, Betonica officinalis, and Salvia verticillata have shown to exhibit the antiviral activity against influenza virus subtype H3N2. The ethanol extract of Betonica officinalis showed the highest virus neutralizing activity against the H3N2 subtype (NI 4.25). The chemical analysis of the aerial parts of plants of the Lamiaceae family has shown that Dracocephalum nutans contains the highest amount of flavonols (4.47 ± 0.04%); the highest content of tannins has been found in Mentha arvensis (17.62 ± 0.78%), and the highest content of catechins has been found in Nepeta cataria (0.43 ± 0.007%). Thus, the plant extracts of the Lamiaceae family are promising sources for further studies to develop new antiviral drugs.

The work is devoted to the study of the phytochemical composition of subcritical extracts of the underground part of aconite high (Aconitum septentrionale L.). The samples of roots and rhizomes of Aconitum septentrionale grown in the Altai Republic were studied. The quality characteristics of plant biomass were determined: moisture content, ash content, quantitative content of biologically active substances extracted by methods of sequential extraction and sequential processing of plant materials under subcritical conditions. The group composition of biologically active substances of Aconitum septentrionale has been established. The quantitative content of biologically active substances of alkaloid nature isolated from the roots and rhizomes of Aconitum septentrionale by different methods was determined. It is shown that the content of alkaloids extracted under subcritical conditions for 2 h is higher than those extracted by maceration for 16 h. A formulation has been developed to create a cream gel based on extracts of Aconitum septentrionale extracted in various ways. The physico-chemical parameters were analyzed and the effectiveness of cream-gels developed using extracts obtained by various methods from the roots and rhizomes of high aconite was revealed. The data presented in the article are of interest for the creation of biologics based on extracts of Aconitum septentrionale, promising for use in the pharmaceutical industry.

A new approach to enhanced specificity and product yield of polymerase chain reaction is proposed. It is based on control of DNA polymerase activity during PCR by changing the magnesium ion concentration, which depends on the temperature of the reaction mixture. A slightly soluble magnesium salt, magnesium oxalate, whose solubility depends on temperature, was used as a source of magnesium ions. During PCR, magnesium oxalate was maintained at saturating concentration by the presence of an insoluble excess of this salt, and the concentration of magnesium ions depended on the salt solubility: binding of magnesium ions at lower temperatures and their release at higher temperatures was shown to affect the DNA polymerase activity and to favor the specific PCR amplification of the target DNA fragment.

The enhancer activity of four DNA fragments previously identified within a 1-Mb region of human chromosome 19 has been investigated. All the fragments have similar tissue-specific profiles: The greatest enhancer activity is observed in HEK293, and the least, in HeLa cells. The enhancers have clear specificity towards the cytomegalovirus promoter in comparison to the SV40 promoter. Functional dissection of one of the fragments (enhancer 14) has shown that only its inner 127-bp part possesses enhancer activity. It is reasonable to suggest that negative regulators, i.e., silencers or insulators, are present in flanking regions of enhancer 14 and limit its effect on the promoter. The activity of enhancer 14 depends on its orientation relative to the promoter, which is uncommon for enhancer elements. The inner 127-bp fragment contains 11 transcription factor binding sites, and 8 of them are factors involved in immune system regulation. Enhancer 14 is located 500 bp upstream of the transcription start site of the TYROBP (DAP12) gene, which codes for a T-killer cell activator protein. It most likely serves as a tissue-specific enhancer for this gene.

Lasting contact of medical personnel in tuberculosis departments with the pathogen of Mycobacterium tuberculosis causes changes in their immune system, which is aimed at adapting the body to a constant antigenic load. Changes in the blood of medical staff indicate the participation of certain cells in the formation of protective immunity. Therefore, the observed changes are likely to be specific and reflect the formation of the protection of a healthy person’s organism from the development of tuberculosis. The question of the relevancy of the use of medical personnel blood parameters as a control over the health status of chronic tuberculosis patients is discussed. The most pronounced changes were observed in populations of monocytes and CD4+ T cells, which are directly involved in the protection of the human body against tuberculosis. The number of CD4+ T cells capable of producing interferon-gamma (IFN-γ) in response to stimulation by M. tuberculosis antigens was analyzed in the blood of medical personnel. The number of these cells in the blood of the medical staff varied depending on the duration of their work in clinic. Low level of CD4+ (IFN-γ)+ activated T cells in the blood of employees after 5–7 years of work can be a prognostic factor for low resistance to tuberculosis.

In this work it is shown that the bienzyme lipase/lipoxygenase system can function in reversed micelles of bis(2-ethyl)hexyl sulfosuccinate (AOT) in octane. As a lipase substrate, a fish fat preparation (fat of sea mammals) with a high content of polyunsaturated fatty acids was used. It was demonstrated that the bienzyme reaction proceeded in a stationary mode and had a rate-limiting step catalyzed by lipase. Under optimal conditions, the efficacy of functioning of the bienzyme system was by an order of magnitude higher than that in water. The lipase/lipoxygenase bienzyme system can be used as a new method of spectrophotometrical determination of lipase activity.

Changes in the level of oxidative damage to proteins in CD1 outbred mice γ irradiated with a dose of 3 Gy have been studied. The changes were estimated from the amount of carbonyl groups (CG) in the proteins. It was found that two hours after exposure to γ radiation, the amount of CG in the cytoplasmic and nuclear fractions of the liver, heart, brain, and spleen sharply increased. Two months after irradiation, the level of CG in the cytoplasmic and nuclear subcellular fractions of the liver and brain decreased to the level of CG in the control animals, which were not exposed to radiation. In the subcellular fractions of the heart and spleen, the increase in the degree of damage was more significant and a high level of damage was observed even two months after irradiation. An enhancement of the antigenic properties of proteins from the liver, heart, and spleen in the postirradiation period was found. Spleen proteins were most immunogenic. A comparison of the antigenic properties of proteins isolated from the tissues 60 days after irradiation revealed a correlation between the level of oxidative damage and the immunogenicity of the total protein fraction.

The chemical structure of lipid A, from the marine γ-proteobacterium Pseudoalteromonas haloplanktis АТСС 14393Т, a main product of lipopolysaccharide hydrolysis (1% AcOH), was determined using chemical methods and NMR spectroscopy. The lipid A was shown to be β-1,6-glucosaminobiose 1,4′-diphosphate acylated with two (R)-3-hydroxyalkanoic acid residues at C3 and C3′ and amidated with one (R)-3-hydroxydodecanoyl and one (R)-3-dodecanoyloxydodecanoyl residue at N2 and N2′, respectively.