A novel acid-catalyzed domino reaction of 2-(2-methoxyphenyl)-substituted cycloalkanols with aromatic and heteroaromatic ortho-aminonitriles was developed, resulting in the diastereoselective formation of new polycyclic acridines and related heterocycles, including partially hydrogenated quinolino[4,3,2-kl]acridines, cyclopenta[5,6]pyrido[4,3,2-kl]acridine, and fused pyrido[4,3,2-gh]phenanthridines, in 14-81 % yields. The developed domino sequence involves initial dearomative electrophilic ortho-spirocyclization via the Ritter reaction, followed by intramolecular nucleophilic trapping of the spiro-r-intermediate by the amino group and subsequent aromatization via [1,2]-alkyl shift. Several of the synthesized quinolino[4,3,2-kl]acridines showed high antibacterial activity against S. epidermidis ATCC 29887 and M. smegmatis mc2 155.

For the first time, a synthetic route for preparing lupane and oleanane derivatives with a hydrogenated furan ring as a cycle A of triterpene scaffold is described. Most of the synthesized compounds, furanoterpenoids and their synthetic intermediates, were non-toxic against the tested cancer and non-cancerous cell lines, and evinced significant inhibitory activity with IC50 1.0-9.0 mu M in the tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibition test. Lupane derivatives - 1-oxime 7, 1,10-seco-hydroxynitrile 11 and furanoterpenoid 14 - were selected as those expected to be the most promising compounds. The results of molecular modeling evinced the strongest binding of compound 11 to the active site of Tdp1 compared to the reference drug. Simultaneously, only compound 11 at subtoxic concentration (10 mu M) produced a synergetic effect on the topotecan activity against HeLa-V cells.

Escherichia coli are generally resistant to the lantibiotic’s action (nisin and warnerin), but we have shown increased sensitivity of E. coli to lantibiotics in the presence of subinhibitory concentrations of polymyxins. Synergistic lantibiotic-polymyxin combinations were found for polymyxins B and M. The killing of cells at the planktonic and biofilm levels was observed for two collection and four clinical multidrug-resistant E. coli strains after treatment with lantibiotic-polymyxin B combinations. Thus, 24-h treatment of E. coli mature biofilms with warnerin-polymyxin B or nisin-polymyxin B leads to five to tenfold decrease in the number of viable cells, depending on the strain. AFM revealed that the warnerin and polymyxin B combination caused the loss of the structural integrity of biofilm and the destruction of cells within the biofilm. It has been shown that pretreatment of cells with polymyxin B leads to an increase of Ca 2+ and Mg 2+ ions in the culture medium, as detected by atomic absorption spectroscopy. The subsequent exposure to warnerin caused cell death with the loss of K + ions and cell destruction with DNA and protein release. Thus, polymyxins display synergy with lantibiotics against planktonic and biofilm cells of E. coli , and can be used to overcome the resistance of Gram-negative bacteria to lantibiotics.

As part of paleogeographic studies on the Curonian Spit (geological section GS 024), a coastal section was studied from the sea in the area of the village of Lesnoy in the place where relict lagoon oozes come out. The granulometric, chemical, and mineral compositions of slope sands were studied for the first time. Heterogeneous conditions for the formation of sand strata were confirmed. A high probability of a secondary change in the composition of sediments as a result of weathering processes was revealed. The results of the study indicate a gradual advance of sand deposits on the coastal part of the lagoon, which began about 10 ka ago. Differentiation of the sand stratum into lower and upper parts with respect to an interlayer marker of coarse-grained sand identified in the section may reflect different stages of generation of the sand stratum: from an alleged shallow-water swell formed during sea level rise to beach and eolian sands.

Oleanane aldehyde-β-enone (OA), being the semi-synthetic derivative of the triterpenoid betulin, effectively inhibits the proliferation of HBL-100 and K562 cancer cells (IC50 0.47-0.53 µM), as well as the proliferation of their resistant subclones with high P-gp expression HBL-100/Dox, K562/i-S9 and K562/i-S9_Dox (IC50 0.45-1.24 µM). A molecular docking study, rhodamine efflux test, synergistic test with Dox, and ABC transporter gene expression were used to investigate the ability of OA to act as a P-gp substrate or inhibitor against Dox-resistant cells. We noted a trend toward a decrease in ABCB1, ABCC1 and ABCG2 expression in HBL-100 cells treated with OA. The in silico and in vitro methods suggested that OA is neither a direct inhibitor nor a competitive substrate of P-gp in overexpressing P-gp cancer cells. Thus, OA is able to overcome cellular resistance and can accumulate in Dox-resistant cells to realize toxic effects. The set of experiments suggested that OA toxic action can be attributed to activating intrinsic/extrinsic or only intrinsic apoptosis pathways in Dox-sensitive and Dox-resistant cancer cells, respectively. The cytotoxicity of OA in resistant cells is likely mediated by a mitochondrial cell death pathway, as demonstrated by positive staining with Annexin V-FITC, an increasing number of cells in the subG0/G1 phase, reactive oxygen species generation, mitochondrial dysfunction, cytochrome c migration and caspases-9,-6 activation.

A series of ligands were synthesized by crotonic condensation of nicotinaldehyde at the C(2) position of various tritepenoids and were then involved in the complex formation with Pd II to prepare finally five new compounds. The cytotoxic activity evaluation in the A549 cell line (adenocarcinomic human alveolar basal epithelial cells) and the HeLa cell line (human cervical carcinoma cells) using the MTT assay demonstrated that methyl 3-oxo-2-(pyridin-3-ylmethylidene)-lup-20(29)-en-28-oate exhibits moderate cytotoxicity (IC 50 is 17.34–20.02 µmol L −1 ).

Abstract—The effects of plasma subplantation of nitrogen ions with energies up to 0.5 keV on the properties of elastic polyurethane (with an elastic modulus of 30 MPa) have been investigated. As a result, the structure and mechanical properties of a surface layer with the thickness of several nanometers were altered. Polyurethane has phase separation into hard and soft phases; modified surfaces are also not mechanically homogeneous. Due to their enhanced hydrophobicity and an increase in surface energy, the treated materials showed higher adsorption capacity for albumin and a reduced number of viable E. coli bacteria. A slight increase in the stiffness of the modified layer (by a factor of 1.5–2.0 compared to untreated material) made it possible to prevent surface damage before deformation (at least 50% of strain).

For the first time, the results of a study of ore sands formed during storm waves and winds on the sea beach of Curonian Spit and in the quieter wind environment on the beach of the Curonian Lagoon are presented. The mineral composition and the sources of their supply to the beaches have been determined. Conclusions are given on the practical and theoretical significance of the ore content of the sands.

We have summarized the results of studies of bottom rock material in Quaternary sediments in the polar seas of the Arctic, North Atlantic, and Antarctica, obtained by sieve washing on expeditions of the Shirshov Institute of Oceanology, Russian Academy of Sciences. We have compiled maps of the quantitative distribution of this material over water areas and created pie charts of the petrographic composition for various sites. A wide variety of petrographic types of rocks has been revealed, caused by their transport by glaciers, icebergs, and ice from glaciation centers on continents and islands. We have identified petrographic provinces based on the composition of the rock material and determined its sources. At the same time, great importance has been given to searching for marker rocks, making it possible to correlate the rock material of the seas with their land sources.

Copolymers of N,N-diallyl-Nʹ-acetylhydrazine and N,N-diallyl-Nʹ-benzoylhydrazine with acrylic acid, acrylonitrile, and acrylamide were synthesized by radical copolymerization in the presence of a radical initiator azobisisobutyronitrile. The borohydride method was used to produce new polymer nanocomposites containing silver nanoparticles 31–55 nm in size, stabilized by synthesized copolymers of N,N-diallyl-Nʹ-acylhydrazines. The presence of heteroatomic fragments and functional groups (carboxyl, amide, nitrile, acetyl, benzoyl, hydrazine) in the polymer chain promotes specific interaction with silver particles, regulating the particle size at the nanoscale and ensuring their uniform distribution in the polymer matrix. Structural features of nanocomposites were investigated using UV, IR, NMR spectroscopy and scanning electron microscopy. The produced nanocomposites exhibit cytotoxic activity against MS melanoma cells and RD rhabdomyosarcoma cells and are promising as new-generation drugs intended for the treatment of cancerous tumors.

Semi-synthetic A-cycle modified triterpenic derivatives with A-cycle condensed with a heterocyclic fragment (compound 1) and fragmented A-ring (compound 2) were tested for cytotoxicity against several tumor cell cultures and doxorubicin (Dox)-resistant cell lines. The equal cytotoxicity of the tested compounds to the parental tumor cell lines (HBL-100, K562) and their resistant subclones (HBL-100/Dox, K562/i-S9) was revealed. The overexpression of ABCB1 (MDR1) gene and P-glycoprotein (P-gp) was confirmed for both resistant subclones of tumor cells. Compounds 1 and 2 were shown to inhibit the ABC-transporter gene expression (MDR1, MRP, MVP, and BCRP) and the transport of well-known P-gp substrate Rhodamine 123 from resistant cells. The docking of triterpenoids 1 and 2 into the drug binding site of P-gp revealed a similarity between the conformation of the tested triterpenoids and that of classical inhibitor verapamil, thus assuming these compounds to be more likely the inhibitors than the substrates of P-gp. Any tested triterpenic derivatives, when combined at non-toxic concentrations with doxorubicin, improved cytotoxic effect of the therapeutic drug against resistant subclones of tumor cells.

Background: Nontuberculous mycobacteria (NTM) form two types of biofilms: Bottom biofilm and pellicle. The spatial distribution of cells between these types of biofilms and their dispersion into the liquid medium depends on the ratio of the nutrient components of the growth medium. The inhibition of biofilm formation by NTM can be achieved through the use of lipophilic compounds, such as essential oils (EOs). Method: The biofilm and pellicle formation of Mycobacterium smegmatis and Mycobacterium avium on four nutrient media under static conditions and in the vapors of six EOs was evaluated by conventional method. The antimycobacterial effect of EOs was also studied by the disc diffusion method. Results: The bottom biofilm and pellicle formation of NTM largely depended on the composition and availability of nutrients. Nutrient media in which NTM form powerful bottom biofilm or pellicle or both have been determined. The growth of studied NTM strains on agar was highly sensitive to the EOs of Scots pine, Atlas cedar, bergamot, and a mixture of EO of different plants. The cultivation of bacteria in the EO vapors also resulted in total suppression of the pellicle for all studied NTM strains. Conclusions: Our data clearly indicate that the carbon-nitrogen ratio is involved in the regulation of the spatial distribution of the biofilm. The preventing effect of EOs vapors, especially the synergistic action of mixture of EOs on the biofilm and pellicle formation by NTMs can be observed.

Исследовано влияние плазменной субплантации ионов азота с энергией до 0.5 кэВ на свойства упругого полиуретана (модуль упругости 30 МПа). В результате обработки изменяются структурно-механические свойства поверхностного слоя материала толщиной в несколько нанометров. Полиуретан имеет фазовое разделение на жесткую и мягкую фазы; модифицированные поверхности также не являются механически однородными. Благодаря увеличению гидрофобности и энергии поверхности обработанные материалы показали улучшенную сорбционную активность к альбумину и снижение количества жизнеспособных бактерий кишечной палочки. Незначительное увеличение жесткости модифицированного слоя (в 1.5-2.0 раза по сравнению с необработанным материалом) позволило избежать повреждения поверхности при растяжении до деформаций не менее 50%.

The Quaternary sediments of the Barents Sea contain a large amount of coarse clastic bottom rock material (BRM), with varying degrees of grain roundedness. Its study is important in determining the type and composition of the earth's crust, with paleogeographic constructions and revealing data on the dynamics of the ice cover. Studies of the Barents Sea BRM began in the 20s of the last century. During this period, were formed basically two hypotheses about the relationship between the distribution of BRM with elements of the sea topography and bedrock exposure. One of them considers BRM a marker suitable for identifying petrographic provinces at the bottom of the Barents Sea [Klenova, 1960]. In this chapter, on the basis of new up-to-date data obtained in 67 and 68 cruises of the RV Akademik Mstislav Keldysh in 2016–2017, the grain size, petrochemical and mineral compositions of BRM are estimated, their distribution patterns are given, transportation methods are analyzed and its feasibility is evaluated use in geological mapping. 4,193 samples were processed in Quaternary sediments, among which 86 reference types were identified. It was shown that the diversity of the composition of the Barents Sea BRM depends on glacial and ice-ice spacing. Therefore, the use of BRM for geological mapping of the bottom of the Barents Sea is unsuitable. The petrographic composition of the BRM in different regions of the Barents Sea is subject to significant fluctuations, but in general it is complementary to the set of rocks in the areas of demolition of adjacent land and depends on the extent of exaration and the removal of exaration material by the glacier to sedimentation areas.

Plasma treatment of polymers has many perspective applications in biomedical area. Carbon or carbon-like coatings of elastic polymers are of interest. However, deformation of the polymeric substrates easily damages the modified surface. Such flaws cancel all the benefits of the treatment and should be avoided. In this paper, a surface of elastic polyurethane (PU) (elastic modulus is 25 MPa) is treated by plasma-enhanced chemical vapor deposition (PECVD) of acetylene/argon. As a result, inhomogeneous carbon-containing nanolayers are formed: discontinuous and solid coatings with heterogeneous stiffness and thickness (from 2 to 11 nm). Structural peculiarities and relatively low elastic modulus (several GPa) of the coatings prevent their fracture under uniaxial deformation of at least up to 50% (however, the thickest coating is covering by a mesh of local nanocracks). The coatings have improved biomedical properties: better albumin adsorption and resistance to bacteria ofEscherichia coli.

The article Is devoted to the study of biological properties of antibiotic-resistant bacteria Propionibacterium acnes and their sensitivity to antibacterial cationic peptides varnerin and hominin. P.acnes Ac-1450 strain resistant to rifampicin and tetracycline were obtained by selection. With the help of the Kirby-Bauer disk diffusion test, it is shown that the acquisition of resistance to these antibiotics is accompanied by a decrease in the sensitivity of bacteria to a number of other antibacterial drugs. As a result of the determination of the minimum inhibitory concentrations of cationic peptides, it has been established that the sensitivity of antibiotic-resistant P.acnes strains to varnerin and hominin is maintained at the sensitivity level of the parent strain. Antibiotic-resistant bacteria show a more pronounced ability for adhesion and biofilm formation in comparison with the bacteria of the parent strain, however, the formation of biofilms can be effectively suppressed by staphylococcins. Analysis of the curves of the formation intensity of P.acnes biofilms, depending on the content of peptides in the medium, made it possible to establish concentrations that inhibit the growth of biofilms by 50%. Despite the fact that the values obtained were 5-12 times higher than the MIC values for planktonic culture of P.acnes, staphylococcins are promising drugs for combating infections caused by propionic bacteria.

Background: Mycobacterium smegmatis and other nontuberculous mycobacteria (NTM) are widely distributed in the environment, but a significant increase of NTM infections has taken place in the last few decades. The objective of this study was to determine the role of toxin–antitoxin (TA) vapBC and mazEF systems that act as effectors of persistence in the stress response of NTM. Methods: The growth ability and the biofilm formation of NTM were evaluated by conventional methods. Bacterial cell viability was determined using MTT staining, agar plating, or the method of limiting dilutions. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of antibiotics were estimated using broth and agar dilution methods. Results: Despite a comparable growth dynamics and biofilm formation on solid/liquid interface with the wild type, a M. smegmatis vapBC, mazEF, and vapBC × mazEF deletion mutant produced more abundant pellicle and were more susceptible to heat shock. Significant differences were also found in the resistance wild type of NTM to isoniazid and ciprofloxacin reflected by higher MBC/MIC ratios. The proposed method of cultivation of agar blocks without visible growth after MIC determination into a liquid medium allows us to detect transition of all wild type of NTM strains to a dormant state in the presence of subMICs of isoniazid and ciprofloxacin while all deletion mutants failed to form dormant cells. Conclusion: Our data suggest that both vapBC and mazEF TA systems putatively involved in the heat and antibiotic stress response of NTM via their key role in transition to the dormant state.

Plasma modification is an efficient method for improving surface characteristics of polymers. In a case of soft polymers, the external deformation of a soft substrate can easily damage the treated surface. This generates a need for new treatment techniques and a detailed investigation of the mechanical properties of the modified surface. In this work, inhomogeneous carbon nanolayers were deposited by magnetron sputtering on preliminary activated in argon plasma surface of elastic polyurethane. The specific features of the coatings (wettability, stiffness, thickness and structure) depend on the complex composition of the initial polymer. The treated surfaces demonstrate improved albumin adsorption and good deformability. It is shown that no strain-induced damage, typical of similar thicker/stiffer coatings, occurs because of the low stiffness and non-uniform structure of the obtained coatings.