The design and search for new selective inhibitors of CA II with a better pharmacological profile, which would cause minimal electrolyte disturbances in the body, remains an urgent problem of medical ...chemistry and pharmacology today. It is important that the discovered new classes of inhibitors do not always contain the main “pharmacophoric” function (sulfamide), which is characteristic of “classic” drugs (Acetazolamide, Methazolamide, Ethoxzolamide, Dorzolamide and others), but are derivatives of phenols, polyamines, coumarins/thiocoumarins, ureas, thioureas, hydroxamates, etc. These molecules also bind in the active site of the enzyme, but do not interact directly with the catalytic zinc ion or interact through zinc-coordinated water molecules/hydroxide ion. However, this leads to an increase in their selectivity and, as a result, pharmacological action. Continuing the search for compounds that affect urination, we were interested in aroylhydrazones of esters of quinone oxime. Firstly, they are characterized by certain structural features (dynamic and geometric isomerism); secondly, they exhibit redox properties; thirdly, the presence of aromatic fragments makes it possible to create a voluminous combinatorial library for analysis. These compounds are ligands in complexation reactions, and an additional increase in the number of hydrogen acceptors in the molecule due to structural modification will improve ligand-enzymatic interactions with carbonic anhydrase (CAII) and, as a result, reveal new promising diuretics. The aim – design and search for potential diuretics (CA II inhibitors) among aroylhydrazones of esters of quinone oxime using in silico, traditional synthesis and in vivo methodologies. Methods of organic synthesis, physico-chemical methods of analysis of organic compounds (NMR 1H-spectroscopy, elemental analysis). Prediction of affinity to the biological target, prediction of toxicity and lipophilicity of the combinatorial library of benzohydrazides O-aroyl esters of quinone oxime using computer services. The study of compounds affecting the excretory function of rat kidneys was carried out according to the generally accepted method of E.B.Berkhin with water load. The investigation of the probable mechanism was carried out using flexible molecular docking, as an approach to search for molecules that have affinity for human carbonic anhydrase type II (CA II). Macromolecular data of the crystal structure of CA II (PDB ID – 3HS4) were downloaded from the Protein Data Bank (PDB). The design was developed and the search for diuretic agents among benzohydrazides of O-aroyl esters of quinone oximes was developed using in silico methods (prediction of affinity, lipophilicity, toxicity and enzyme-ligand interactions), traditional organic synthesis, and in vivo methods (effect on excretory function of rat kidneys). The synthesis of benzohydrazides of O-aroyl esters of quinone oxime was carried out by the interaction of aroylhydrazines with 4-(aroylimino)cyclohexa-2,5-dien-1-ones. The structure of the synthesized compounds was confirmed by elemental analysis and 1H NMR spectra. Studies of the effect of synthesized compounds on the excretory function of rat kidneys allowed us to identify a number of promising compounds among aroylhydrazones of quinonexime esters, which increase daily diuresis by 54.2-352.8% compared to the control group. At the same time, it was established that the most active was N'-(4-(2-chlorobenzoyloxy)iminocyclohexa-2,5-dien-1-ylidene)-3-nitrobenzohydrazide, which increased daily diuresis by 352.8% in comparison with the control group, while exceeding the effect of “Hydrochlorothiazide” (170.8%). The developed and implemented strategy for the search for diuretics among benzohydrazides of O-aroylesters of quinone oxime allowed the identification of an effective compound, which in terms of diuretic effect exceeds the comparison drug “Hydrochlorothiazide”. Visualization of the molecular docking of the active compounds showed that their geometry makes it difficult to place them in the pocket of the active site of CA II, but the pronounced diuretic effect can also be associated with their ability to form coordination bonds with the zinc cation. The obtained results justify the further targeted search for potential diuretics among this class of compounds for a more detailed understanding and study of the mechanism of action.
The image of a falcon in “The Tale of Igor’s Campaign” and ancient Chinese literature is analyzed. The material for the study was the original text of “The Tale”, its translations and comments to ...them by Chinese literary scholars Wei Huangnu and Li Xiyin, as well as famous ancient Chinese works. One of the main motives of the artistic and pictorial ornithology of “The Tale” is examined in detail — the individual and personal images of the falcons-Russian princes, opposing the spontaneity, chaos of the bird flock as an enemy horde. In ancient Chinese literature, the ornithological figurative complex serves as a symbol, firstly, of elite divisions, strong troops; secondly, a person filled with high motives, both heroic and career ambitious; thirdly, the authority of the monarch or some other important person in power. The novelty of the research is seen in the fact that for the first time the mythologeme falcon of “The Tale” is considered in intertextual comparison with the works of ancient Chinese literature. It is concluded that the symbolic connotations of the falcon both in ancient Chinese literature and in “The Tale of Igor’s Campaign” are closely related to the real qualities of this bird’s behavior in its natural environment: bravery, courage, dexterity.
The modification of lead-compound aimed to the increasing of activity, decrement of toxicity or improvement of selectivity is one of the most important methods used for elaboration of novel ...medications. Natural compounds, approved or investigational drugs or just compounds with proved biological activity could be the lead-compound. Often the chemical modification of lead compounds is directed at the enhancement of ligand-biological target interactions. Abovementioned approach, namely structural modification of known drug triamterene was used for purposeful search for novel diuretics. The preliminary prognostication of ligand-target interactions and affinity levels allow to reduce quantity of experimental animals, synthesis, and pharmacological studies costs. Conducted studies revealed the series of promising 6,7-disubstituted pteridine-2,4(1H,3H)-diones with diuretic activity that comparable with pharmacological effect of triamterene. Aim – purposeful search for promising diuretics among structural analogues of triamterene that includes preliminary in silico studies, synthesis and in vivo screening of novel compounds for diuretic activity. Methods used: organic synthesis, physicochemical methods of analysis of organic compounds (NMR 1H-spectroscopy, chromato-mass spectrometry, elemental analysis). Prediction of affinity for a biological target, prediction of toxicity and lipophilicity of the combinatorial library, which was created on the basis of the drug triamterene, was carried out using computer services. Studies of compounds that affect the excretory function of the kidneys of rats were performed according to the generally accepted method of E.B. Berkhin with water load. Research of the probable mechanism was conducted by flexible molecular docking, as an approach of finding molecules with affinity to a specific biological target. Macromolecular data were downloaded from the Protein Data Bank (PDB) namely, the crystal structures of epithelial sodium channel (ENaC) ((PDB ID – 6WTH). The substantiation of potential diuretics design was conducted by in silico methods (prediction of affinity, ligand-enzyme interactions and pharmacokinetic characteristics). The structural modification of triamterene molecule was carried out by replacing of amino-group in positions 2, 4 and 7 by others “pharmacophore” fragments. Abovementioned transformation is aimed at the changing of ligand-enzyme interactions in active site, lipophility and toxicity. Synthesis of 6,7-disubstituted pteridine-2,4(1H,3H)-diones was conducted by condensation 5,6-diamino-2-oxo-(thioxo-)-2,3-dihydropyrimidin-4(1H)-ones with carbonyl-containing compounds or oxocarboxylic acids. The further modification of obtained compounds was performed by alkylation, hydrazinolysis and nucleophilic addition/elimination. The structure of obtained compounds was proven by elemental analysis, chromato-mass and 1H NMR-spectral analysis. The studies of synthesized compounds effect on excretion function of kidneys allowed to detect series of promising structural analogues of triamterene that exceed it in pharmacological activity by 27.3-99.0%. The “structure-biological activity” relationship was discussed and perspective of the further search of diuretics among abovementioned compounds were shown. The design of new biologically active compounds with diuretic activity was performed using in silico methodologies and realized by structural modification of the well-known diuretic triamterene. Traditional organic synthesis was used for preparation of target compounds, in vivo experiments were used to detect compounds with significant biological activity. Several effective compounds were identified among pteridines, which exceed the reference drug triamterene in terms of daily diuresis. The obtained results substantiate further purposeful search, in-depth research on experimental pathologies and study of the mechanism of action of potential diuretics among this class of compounds.
This paper presents the calculation of non-stationary non-sinusoidal mode of the power supply system (PSS) under the condition of current resonance (parallel resonance). Evaluation of the need for ...higher harmonics (HH) filtering was carried out. To achieve this, measurements of the actual level of HH and other unified power quality indexes were conducted, and oscillograms of the network mode parameters and HH spectrum were constructed. The measurement of unified power quality indexes was carried out with certified and calibrated power quality analyzers Metrel 2792A. These instruments satisfy the effective world standards on power quality and other reference documentation. Resonance frequencies where resonance modes emergence is possible were determined by calculation. Maximum overvoltage ratios for different points of the examined PSS were also determined.
Iron oxide nanopowders are synthesized via chemical precipitation. It is shown that synthesis produces an iron oxide phase with a magnetite structure (either a magnetite–maghemite solid solution or a ...mixture of this solid solution and goethite). The sizes of the CSR and particles for the main phase are ~10–20 nm. The synthesized iron oxide powders have developed surfaces, specific surface area
S
BET
≈ 92 and 117 m
2
/g, and identical fairly large specific pore volumes (
= 0.35 cm
3
/g). It is shown that additional in situ ultrasonic treatment of the magnetic iron oxide nanoparticles in the mother liquor results in abrupt oxidation of iron(II) ions and creates a nonmagnetic impurity phase of goethite.
The peculiarities of the corrective effect of bee pollen on the indicators of the immune system (non-specific resistance and the immune system) of 56 conditionally healthy women living under constant ...exposure to low-intensity ionizing radiation of natural and man-made origin in the city of Kropyvnytskyi, Kirovohrad region, were investigated. To determine the probable radio-modification, bee pollen from the spring collection was used. The work used immunological methods of the 1st level, in-depth studies of cytomorphological changes of neutrophils and lymphocytes, as the main elements of the immune system, and also determined the hidden insufficiency of the immune system. The conducted studies showed the presence of a positive corrective effect of the course of bee pollen introduced into the diet on the indicators of non-specific resistance and the immune system in the case of the combined permanent effect of natural and man-made low-intensity radiation on the body of conditionally healthy women. The obtained corrective effect is manifested by the normalization or tendency to normalize the indicators of the cellular link of non-specific resistance to its restoration and reduction of the frequency and severity of the existing and hidden insufficiency of the content of lymphocytes, positive shifts in the number of intact and functioning neutrophils. The mechanisms of the corrective effect of bee pollen on the indicators of the immune system have been established. They include: a detoxification effect, a decrease in the level of inflammation, an increase in the number of functionally capable cells in the pool of neutrophils and lymphocytes.
A new method of correlation signal processing with symmetric heterodination is presented, which is a development of the two-band processing method. The proposed processing method allows you to use ...all the advantages of two-band processing when receiving signals of any type, from broadband to monochromatic.
Catalytic properties of Fe-MIL-101 and Cr-MIL-101 metal-organic frameworks in the solvent-free oxidation of cyclohexene and alpha-pinene with molecular oxygen have been explored. Both catalysts allow ...alkene oxidation under mild conditions (1 bar O-2, 40-60 degrees C) and afford allylic oxidation products. The nature of catalysis and the product distribution strongly depend on the nature of the transition metal. Cr-MIL-101 behaves as truly heterogeneous catalyst to give predominantly alpha,beta-unsaturated ketones. Catalysis over Fe-MIL-101 has true heterogeneous nature only at 40 degrees C, producing mainly 2-cyclohexene-1-ol. At 50-60 degrees C, iron leaching into solution occurs, leading to cyclohexenyl hydroperoxide as the major product. Under optimal conditions, both catalysts can be reused several times without suffering a loss of the catalytic properties. Rate-retarding and rate-accelerating effects of inhibitors and initiators, respectively, indicate radical chain mechanism. Different pathways for transformation of hydroperoxide have been suggested to rationalize the observed differences in the reaction selectivities over Cr- and Fe-MIL-101.
It is shown that the deposition of silica sol shells on the surface of barley seeds based on hydrolyzed tetraethoxysilane with the addition of γ-Fe
2
O
3
(maghemite) nanoparticles leads to a ...nonlinear change in the transparency in the UV region of distilled nonsterile and sterilized water after contact with the treated silica-salt seeds, depending on the concentration of the oxide additive introduced into the silica sol, varying in the range 0.001–10 000 mg/L. A number of correlations are found between the transmittance of the studied water samples and the target indicators of seed germination, which may be due to a change in the permeability and sorption activity of the shell being formed.
The features of tritium adsorption by clay rocks, which mainly consist of clay minerals with high adsorption abilities for tritium oxide (НTO) and super heavy water (T2O), were studied after their ...thermal treatment at a temperature of 105 and 500 °C. The observation was carried out in a closed system "tritiated water - clay rock". Indicators of the dynamics of growth of tritium adsorption by heat-treated clay rocks over 380 days are obtained. It was found that the adsorption of tritium in this observation system actively grows for the first 30 - 40 days for all the studied minerals, and then slows down. White clays retain an increase in adsorption over the entire observation period of 380 days.
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