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A regio- and stereoselective method for the synthesis of (trifluoro(trichloro)methyl)-substituted spiro[chromeno(thia)pyrrolizidineoxindoles] in 53–97% yields was developed on the basis of the three-component reaction of 3-nitro-2-(trifluoro(trichloro)methyl)-2Hchromenes with azomethine ylides generated in situ from isatins and L-(thia)proline in EtOH at 30°C. The obtained compounds demonstrated high cytotoxic activity against HeLa human cervical cancer and RD human embryonic rhabdomyosarcoma cells.

A regio- and stereoselective method for the synthesis of N-unsubstituted 3-aryl-4-(trifluoromethyl)-4H-spiro[chromeno[3,4-c]-pyrrolidine-1,3'-oxindoles] in 24–79% yields, based on the three-component reaction of 3-nitro-2-(trifluoromethyl)-2H-chromenes with azomethine ylides generated in situ from benzylamines and isatins by refluxing in CH2Cl2 for 24 h has been developed. 3-Phenyl-4-(trifluoromethyl)-4H-spiro[chromeno[3,4-c]pyrrolidine-1,3'-oxindoles] were obtained in 36–71% yields via the three-component reaction of 3-nitro-2-(trifluoromethyl)-2H-chromene, isatins, and L-phenylglycine proceeding in EtOH at 60°C for 5 h. The resulting compounds exhibited cytotoxic activity against human cervical cancer HeLa cells in the micromolar concentration range.

A review of recent advances in the development of luminescent inorganic nanoparticles doped with rare earth ions, which can be used for biomedical applications, is presented. Luminescent nanomaterials doped with rare earth ions are characterized by physicochemical properties such as long luminescence time, large Stokes and/or anti-Stokes shifts, narrow luminescence bands, high photostability, and low toxicity. These materials can be considered to be a new generation of biosensors along with conventional molecular probes such as organic dyes, quantum dots, and lanthanide labels based on organic chelates.

The crystal structures of four new chiral [1,2,3]triazolo[5,1-b][1,3,4]thiadiazines are described, namely, ethyl 5′-benzoyl-5′H,7′H-spiro[cyclohexane-1,6′-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine]-3′-carboxylate, C19H22N4O3S, ethyl 5′-(4-methoxybenzoyl)-5′H,7′H-spiro[cyclohexane-1,6′-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine]-3′-carboxylate, C20H24N4O4S, ethyl 6,6-dimethyl-5-(4-methylbenzoyl)-6,7-dihydro-5H-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine-3-carboxylate, C17H20N4O3S, and ethyl 5-benzoyl-6-(4-methoxyphenyl)-6,7-dihydro-5H-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine-3-carboxylate, C21H20N4O4S. The crystallographic data and cell activities of these four compounds and of the structures of three previously reported similar compounds, namely, ethyl 5′-(4-methylbenzoyl)-5′H,7′H-spiro[cyclopentane-1,6′-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine]-3′-carboxylate, C19H22N4O3S, ethyl 5′-(4-methoxybenzoyl)-5′H,7′H-spiro[cyclopentane-1,6′-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine]-3′-carboxylate, C19H22N4O4S, and ethyl 6-methyl-5-(4-methylbenzoyl)-6-phenyl-6,7-dihydro-5H-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine-3-carboxylate, C22H22N4O3S, are contrasted and compared. For both crystallization and an MTT assay, racemic mixtures of the corresponding [1,2,3]triazolo[5,1-b][1,3,4]thiadiazines were used. The main manner of molecular packing in these compounds is the organization of either enantiomeric pairs or dimers. In both cases, the formation of two three-centre hydrogen bonds can be detected resulting from intramolecular N—H...O and intermolecular N—H...O or N—H...N interactions. Molecules of different enantiomeric forms can also form chains through N—H...O hydrogen bonds or form layers between which only weak hydrophobic contacts exist. Unlike other [1,2,3]triazolo[5,1-b][1,3,4]thiadiazines, ethyl 5′-benzoyl-5′H,7′H-spiro[cyclohexane-1,6′-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazine]-3′-carboxylate contains molecules of only the (R)-enantiomer; moreover, the N—H group does not participate in any significant intermolecular interactions. Molecular mechanics methods (force field OPLS3e) and the DFT B3LYP/6-31G+(d,p) method show that the compound forming enantiomeric pairsviaweak N—H...N hydrogen bonds is subject to greater distortion of the geometry under the influence of the intermolecular interactions in the crystal. For intramolecular N—H...O and S...O interactions, an analysis of the noncovalent interactions (NCIs) was carried out. The cellular activities of the compounds were tested by evaluating their antiproliferative effect against two normal human cell lines and two cancer cell lines in terms of half-maximum inhibitory concentration (IC50). Some derivatives have been found to be very effective in inhibiting the growth of Hela cells at nanomolar and submicromolar concentrations with minimal cytotoxicity in relation to normal cells.

A series of new 5-aryl-2,2'-bipyridines and their (polyfluoro)salicylate complexes of Cu(II), Co(II) and Mn(II) were synthesized. Their antimicrobial activity was evaluated in vitro against six strains of Trichophytons, E. floccosum, M. canis, C. ablicans and Gram-negative bacteria N. gonorrhoeae. Among azo-ligands, Ph-bipy and Tol-bipy showed promising antifungal activity (minimum inhibitory concentration (MIC)

Endo-1,3-Dipolar cycloaddition of azomethine ylides generated in situ from 11H-indeno[1,2-b]quinoxalin-11-one and L-proline/thiaproline to (E)-1,5-diarylpent-4-ene-1,3-diones led to the 3-hydroxy-3-aryl-1-(1′-arylspiro[indeno[1,2-b]quinoxaline-11,3′-(thia)pyrrolizidin]-2′-yl)prop-2-en-1-ones containing the 1,3-diketone fragment. Upon processing of these adducts with arylhydrazine hydrochlorides in an acidic medium, the 2′-(1,3-diaryl-1H-pyrazol-5-yl)-1′-arylspiro[indeno[1,2-b]quinoxaline-11,3′-pyrrolizidines] were formed as individual regioisomers. In a similar reaction with hydrazine hydrate and hydroxylamine, the corresponding hybrids bearing the N-unsubstituted pyrazole and isoxazole moieties were obtained. Most of spiro[indenoquinoxaline-pyrrolizidine]-N-arylpyrazole conjugates have shown high cytotoxic activity against the HeLa cancer cell line.

The possibility of using the transverse relaxation time T2 of protons in aqueous media for quantitative measurement of the capture of magnetic nanoparticles by cells has been studied and demonstrated. The measurement of T2 was performed on a portable original NMR relaxometer with a measuring cell for a standard well of a biological plate. The novelty of the approach is that quantitative measurements of the capture kinetics were carried out using measurements of the proton relaxation time of the nutrient medium, which is determined by the remaining number of magnetic particles (not captured by the cells) in the medium. To study the kinetics of capture, two types of magnetic nanoparticles were synthesized: magnetite particles Fe3O4 and composite particles Fe@C with an iron-carbon shell structure. The surface of the particles was functionalized with amine-and carboxyl groups. The capture of aminated particles of Fe@C cells is established by microscopy and NMR-relaxometry by measuring the time T2. It is shown that the proposed method makes it possible to register very small concentrations of trapped magnetic nanoparticles equal to tens of pg/cell.

The alkylation of 6-(polyfluoro)alkyl-2-thiouracils with 4-bromobutyl acetate in refluxing acetonitrile in the presence of K2CO3 proceeds regioselectively to give S, O-disubstituted pyrimidines as the major products and S,N-isomers as the minor ones, whereas the use of 2-bromoacetophenone as an alkylating agent results in the formation of the S,O-isomer. 6-Trifluoromethyl-2-thiouracil and 2-(2-oxo-2-phenylethylthio)-4-(2-oxo-2-phenylethoxy)-6-trifluoromethyl-pyrimidine exhibited marked tuberculostatic activity. 6-Trifluoromethyl-2-thiouracil did not exert a significant cytotoxic effect on the HeLa cell culture and human dermal fibroblasts.

e-pot nitrosation of 1,3-diketones or their lithium salts followed by treatment of hydrazines. Reduction of the nitroso-derivatives made it possible to obtain the 4-amino-3-trifluoromethylpyrazoles chlorides. Cytotoxic activity of the compounds wase evaluated in vitro

4-Nitroso-3-trifluoromethyl-5-alkyl[(het)aryl]pyrazoles were synthesized via one-pot nitrosation of 1,3-diketones or their lithium salts followed by treatment of hydrazines. Reduction of nitroso-derivatives made it possible to obtain 4-amino-3-trifluoromethylpyrazoles chlorides. According to computer-aided calculations, all synthesized compounds are expected to have acceptable ADME profile for drug design. Tuberculostatic, antibacterial, antimycotic, antioxidant and cytotoxic activities of the compounds were evaluated in vitro, while their analgesic and anti-inflammatory action was tested in vivo along with acute toxicity studies. N-Unsubstituted 4-nitrosopyrazoles were the most effective tuberculostatics (MIC to 0.36 μg/ml) and antibacterial agents against Streptococcus pyogenes (MIC to 7.8 μg/ml), Staphylococcus aureus, S. aureus MRSA and Neisseria gonorrhoeae (MIC to 15.6 μg/ml). 4-Nitroso-1-methyl-5-phenylpyrazole had the pronounced antimycotic action against a wide range of fungi (Trichophyton rubrum, T. tonsurans, T. violaceum, T. interdigitale, Epidermophyton floccosum, Microsporum canis with MIC 0.38–12.5 μg/ml). N-Unsubstituted 4-aminopyrazoles shown high radical-scavenging activity in ABTS test, ORAC/AAPH and oxidative erythrocyte hemolysis assays. 1-Methyl-5-phenyl-3-trifluoromethylpyrazol-4-aminium chloride revealed potential anticancer activity against HeLa cells (SI > 1351). The pronounced analgesic activity was found for 4-nitroso- and 4-aminopyrazoles having phenyl fragment at the position 5 in “hot plate” test. The most of the obtained pyrazoles had a moderate acute toxicity.

A one-pot three-component reaction of azomethine ylides generated in situ from isatins and sarcosine with 3-nitro-2-(trifluoromethyl)-2H-chromenes in i-PrOH at 55–60 °C leads to the kinetically controlled products – exo-spiro[chromeno[3,4-c]pyrrolidine-3,3′-oxindoles]. When this reaction is carried out in 1,4-dioxane under reflux, the thermodynamically controlled endo-spiro[chromeno[3,4-c]pyrrolidine-1,3′-oxindoles] are preferably formed. The isomerization of the kinetic products in DMSO solution at different temperatures has been studied by NMR spectroscopy and the stepwise mechanism of reversible [3+2] cycloaddition has been confirmed. The cytotoxic activity of some CF3-substituted spiro[chromeno[3,4-c]pyrrolidine-oxindoles] against the HeLa cell line was evaluated by the MTT test.

For the culture of normal and transformed fibroblasts, the differential effect of two nanoclusters (Мо72Fe30, Мо132) has been shown. The Мо72Fe30 nanocluster is nontoxic to normal fibroblasts, while the Мо132 cluster shows toxicity to normal and transformed fibroblasts. An analysis of the ultrastructure of the cells under the influence of the nanoclusters has demonstrated the specificity of the changes. The dermal fibroblasts are more resistant to the action of Мо72Fe30; the Мо132 cluster causes extensive disorders in the membrane organelles both in normal and transformed fibroblasts. The results confirm the possibility of applying the Мо72Fe30 nanocluster in biomedicine and the use of the Мо132 nanocluster in oncology.

The information about cellular respiration and metabolism of malignant and healthy cells is presented. The working example of a custom made magneto-therapeutic device allows to realize inhibitory effect on oncopathology. Thus, as a result of the investigations the intense pulse low-frequency magnetic field exposure results to morphofunctional inhibition of HeLa cell line.

Radiation is one of the factors that constantly affects living organisms. The effect of natural radiation background is supplemented by radiation from artificial radioactive sources, the most common of them are medical devices used as diagnostic and therapeutic equipment. The use of radiation therapy is based on different radiosensitivity of normal and pathologically altered organs, tissues and cells of humans and animals. The search and application of substances that change the sensitivity of living organisms to ionizing radiation to reduce the damaging effect on healthy tissues, while maintaining a positive therapeutic effect, is an urgent issue of modern medical radiobiology. Currently, nanoparticles are widely used as such substances. This paper investigates the effect of mesoporous CeO2 nanopowder on the radiosensitivity of rat alveolar and peritoneal macrophages, dermal fibroblasts, and human cervical carcinoma cells. CeO2 nanoparticles were found to have selective radiomodifying properties in relation to various types of cells. CeO2 nanoparticles had a radioprotective effect on human fibroblasts, increasing their viability after irradiation and speeding up the differentiation of fibroblasts. The nanoparticles acted as radiosensitizers on tumor cells and macrophages, enhancing the damaging effect of ionizing radiation, but the mechanism for increasing sensitivity may be different in each case. The unique enzyme-like properties of cerium dioxide nanoparticles require further investigation of the mechanisms of their action on living systems. This can give an impetus to the development of new effective methods of radiotherapy for various diseases.

Was carried out the assessment of photocatalytic, cytotoxic properties on cells and antibacterial properties against E. coli and Staphylococcus of oxides nanopowders with nanoscale silver coating. Is shown the promising use of such composites as a photocatalytic agent, as well as in medicine. © Published under licence by IOP Publishing Ltd. The reported study was funded partially by RFBR and Sverdlovsk region, project 20-48-660019 р_а.

Interactions of bimodal (fluorescent and magnetic) nanoparticles with HeLa cells were studied. The nanoparticles, characterized by high magnetic moment and relaxing capacity, exhibited fluorescence sufficient for their use as labels in confocal microscopy and flow cytometry. Penetration of these nanoparticles into the cell depended on their surface charge: positively charged nanoparticles of this structure penetrated inside, while negatively charged particles were not found in the cells.

Hybrid nanoparticles based on Fe3O4 and CdS combining magnetic and luminescence properties were synthesized. The possibility of visualization of various cells by 3-mercaptopropylsilane-modified CdS nanoparticles and hybrid nanoparticles based on them using a confocal microscope was demonstrated. The synthesized materials did not show a clear-cut cytotoxicity.

This study presents the synthesis and optical properties of a new class of bright green-yellow fluorescent dyes with potential applications in bioimaging. A facile synthetic route via the chelation of aryl(hetaryl)aminoacryloylthiophene scaffolds with a BF2 fragment is presented. The photophysical properties of the dyes are attributed to the nature and position of electron-donating and electron-withdrawing substituents. Upon coordination to a BF2 fragment, characteristic emission was observed, with λem ranging from 503 to 543 nm and quantum yields of 0.14-0.42. Compared with parent aryl(hetaryl)aminoacryloylthiophenes, a significant red shift in absorption (up to 480 nm in solution) and emission (up to 543 nm in solution and 610 nm in the solid state) and high chemical stability and photostability were observed. The electron-accepting character of the substituents on the terminal aromatic ring or replacing this fragment with pyridine or pyrazine moieties resulted in increased quantum yields. To gain insight into the electronic structures and optical properties, quantum mechanical calculations were performed. The results of (TD-)DFT calculations supported the structural and spectroscopic data and showed the features of electronic distribution in the frontier molecular orbitals and active electrophilic and nucleophilic sites in the compounds investigated. Synthesized BF2 complexes are promising dyes for cell imaging and flow cytometry owing to their ready penetration and accumulation in cells.

A series of 1,2,3-triazole derivatives was prepared and their cytotoxic actions on glioma cell cultures were studied. Amethod for the synthesis of 1-R-5-methyl- 1 H-[1,2,3]triazole-4-carboxamides is presented, based on transformation of 4-acetyl-1-phenyl- 1 H-[1,2,3]-triazolate sodium using primary amine hydrochlorides.

3-Cyclopentylidene(cyclohexylidene)amino-3H-1,2,3-triazole-4-thiolates, formed via Dimroth rearrangement of 1,2,3-thiadiazolylhydrazones of cyclopentanone and cyclohexanone in the presence of triethylamine, reacted in situ with α-bromoacetophenones with the formation of spirocyclic 6,7-dihydro-5H-[1,2,3]triazolo[5,1-b][1,3,4]thiadiazines. The effect of the obtained compounds on the viability and proliferative activity of four lines of cell cultures was studied. The selective proliferative activity was determined.

Changes in erythropoiesis during liver regeneration after partial hepatectomy depended on functional activity of phagocytosing mononuclear cells.