Vol 9, No 2 (2021)



Ryabov N.A., Ryzhov V.M., Kurkin V.A., Kolpakova S.D., Zhestkov A.V., Lyamin A.V.


The problem of finding new antimicrobial drugs based on medicinal plant raw materials in modern pharmaceutical practice, is still relevant. There are interesting plant objects that have an antimicrobial action due to the content of a complex of biologically active substances in them. Quercus robur L. is a promising plant object, medicinal plant raw materials of which can be used for the development of new antimicrobial drugs.The aim of the study is screening of the antimicrobial activity of water-ethanolic extractions from Quercus robur L leaves and buds.Materials and methods. The determination of the minimum inhibitory concentration was carried out by the method of double serial dilutions in Mueller-Hinton nutrient broth (Bio-Rad, USA). As test cultures, strains of microorganisms of the American Type Culture Collection (ATCC) were used: Staphylococcus aureus (ATCC 29213), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), as well as Candida albicans (a clinical strain). The incubation was carried out at the temperature of 35°C for 24 hours. Simultaneously, an experiment was carried out to establish a "negative" control. The results were assessed visually by the presence / absence of the growth of microorganisms in test tubes with the corresponding dilutions of the test samples.Results. In the course of the study, it was found out that water-ethanolic extractions of Quercus robur L. leaves have the greatest antimicrobial effect against strains of Staphylococcus aureus and Escherichia coli. The water-ethanolic extractions of Quercus robur L. buds exhibit a pronounced antimicrobial activity against Pseudomonas aeruginosa and Candida albicans strains.It was revealed that the preparation of Quercus robur L. leaves tincture in the raw material:extractant ratio of 1:5 has a pronounced antimicrobial effect on the strains of Pseudomonas aeruginosa, Staphylococcus aureus, and with a higher multiplicity of dilution - on the strains of Escherichia coli and Candida albicans. The drug tincture of Quercus robur L. buds in the raw material:extractant ratio of 1:5 has a pronounced antimicrobial effect on the strains of microorganisms P. aeruginosa, S. aureus, E. coli and C. albicans in an eight-fold dilution. With respect to P. aeruginosa strains, antimicrobial activity was observed in 16-fold dilutions. The most pronounced antimicrobial effect was recorded against the C. albicans strain in a 32-fold dilution.As a result of the study, it can be concluded that to obtain the antimicrobial drugs - tincture of Quercus robur L. leaves and buds - is advisable to use the optimal extractant - 70% alcohol in a raw material:extractant ratio of 1:5. With these parameters of extraction, the greatest antimicrobial effect is observed in relation to the studied strains of the microorganisms. 70% alcohol has also a better penetrating ability into the deep layers of the epidermis in comparison with higher concentrations.Conclusion. The results of the screening analysis of the antimicrobial activity will be used as a justification for the introduction of antimicrobial drugs based on the leaves and buds of the Quercus robur L. in a medical and pharmaceutical practice.
Pharmacy & Pharmacology. 2021;9(2):104-113
pages 104-113 views


Jain E.A., Demchenko D.V., Ozerov A.A., Makarova M.N., Makarov V.G., Balabanyan V.Y.


The aim of the study is to identify 1-[2-(2-benzoylphenoxy) ethyl]-6-methyluracil using various methods of analysis, as well as to study its action mechanism against wild-type and mutant forms of HIV-1 reverse transcriptase (RT).Materials and methods. To characterize the structure of the test substance, a few kinds of analysis (X-ray diffraction, elemental, thermal) as well as a few kinds of spectroscopy (UV, IR, and NMR) have been used. The study of the action mechanism of the compound as a potential drug was carried out by evaluating the inhibitory activity against HIV-1 RT wild-type and its mutant forms corresponding to drug-resistant viral strains.Results. The studies have been carried out to confirm the structure of 1-[2-(2-benzoylphenoxy)ethyl]-6-methyluracil. The UV spectrum has a pronounced absorption maximum when measuring a solution of the substance in tetrahydrofuran at the concentration of 0.10 mg / ml. In the IR spectrum, there are specific bands in the range of 4000-370 cm-1. These factors make it possible to use UV and IR spectra to identify the test compound in the substance. It has also been established that the number and mutual arrangement of functional groups, the integrated intensity of signals in the 1H-NMR spectrum, as well as the structure of the carbon skeleton, correspond to the structure of 1-[2-(2-benzoylphenoxy) ethyl]-6-methyluracil. The results of studying the action mechanism showed that the test compound is an effective inhibitor of wild-type HIV-1 RT with an inhibition constant of 0.2 µM, as well as an enzyme inhibitor (mutation G190A) with an inhibition constant of 8 µM; enzyme (mutation Y181C) with an inhibition constant of 10 µM, as well as a reverse transcriptase (RT) inhibitor (mutation L100I, K103N, V106A) and a double mutant K103N / Y181C with an inhibition constant of more than 20 µM.Conclusion. As a result of the performed X-ray structural, elemental, 1H-NMR and 13C-NMR analyzes, the structure of 1-[2-(2-benzoylphenoxy)ethyl]-6-methyluracil has been confirmed. The possibility of using UV, IR and NMR spectroscopy, as well as thermal analyzes to confirm the authenticity during the verification of 1-[2-(2-benzoylphenoxy)ethyl]-6-methyluracil, has been shown. The developed methods can be used in the quality control and included in the draft of practice guidelines for the investigated substance. The studies of the action mechanism of the compound of HIV-1 RT reverse transcriptase have shown that this compound belongs to the group of non-nucleoside reverse transcriptase inhibitors (NNRTIs) of HIV-1.
Pharmacy & Pharmacology. 2021;9(2):114-129
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Orlova E.A., Umerova A.R., Dorfman I.P., Orlov M.A., Abdullaev M.A.


The aim of the study was to estimate the economic damage by COPD, including direct medical and non-medical costs and indirect costs associated with premature deaths of working-age individuals.Materials and methods. First, estimation of the economic COPD burden in Astrakhan region (AR) was carried out using the clinical and economic analysis of the "cost of illness" (COI). Direct medical costs of inpatient, outpatient, ambulance and emergency medical care, as well as direct non-medical costs associated with the disability benefits payments, were taken into account. Indirect costs were defined as economic losses from undelivered products due to premature deaths of working-age individuals.Results. From 2015 to 2019, the economic COPD burden in AR amounted to 757.11 million rubles in total, which is equivalent to 0.03% of the gross regional product covering a five-year period of the study. Direct medical and non-medical costs totaled 178.02 million rubles. In the structure of direct medical expenses, expenses for inpatient, as well as ambulance and emergency medical care during the study period, increased by 92.5% and 45.5%, respectively. While the costs for the outpatient care decreased by 31.9%, the increase in direct non-medical costs associated with the disability benefits payments, increased by 5.1% (2019). Indirect losses amounted to 579.09 million rubles.Conclusion. The structure of the main damage is dominated by indirect losses in the economy associated with premature deaths of working-age individuals. In the structure of direct medical costs, inpatient care costs prevailed. These studies indicate the need to continue an advanced analysis of the economic burden of COPD, as well as to optimize the treatment and prevention of the exacerbations development of this disease.
Pharmacy & Pharmacology. 2021;9(2):130-138
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Solenova E.A., Pavlova S.I.


The results of studying the effect of isoliquiritigenin on animal survival in the model of staphylococcal infection and the function of human and animal phagocytes are presented in this article.The aim of the investigation was to study the effect of an isoliquiritigenin preliminary administration on the survival of animals against the background of staphylococcal infection, as well as on the function of phagocytes in mice and humans.Materials and methods. To assess the survival of Balb/C mice, a model of infection caused by Staphylococcus aureus J49 ATCC 25923 with the construction of Kaplan-Meier curves, was used. The effect on the phagocytes functions was studied by assessing the peptone-induced migration of phagocytes into the abdominal cavity of Balb/C mice, the absorption activity of phagocytes (neutrophils and monocytes) of human blood, as well as their production of reactive oxygen intermediates (ROIs) using а flow cytometry.Results. It was found out that a preliminary triple intraperitoneal administration of isoliquiritigenin (30 mg/kg) increases the survival rate of Balb/C mice in staphylococcal infection caused by Staphylococcus aureus J49 ATCC 25923. At the same time, isoliquiritigenin dose-dependently activates the production of reactive oxygen intermediates by human neutrophils and monocytes without statistically significantly suppressing a phagocytic activity of monocytes and neutrophils against fluoresceinisothiocyanate-labeled S. aureus J 49 ATCC 25923, as well as peptone-induced migration of phagocytes into the abdominal cavity of mice.Conclusion. Thus, a preliminary administration of isoliquiritigenin increases the survival rate of mice with staphylococcal infection and increases the production of reactive oxygen intermediates by phagocytes. The data obtained, can become the basis for further research of antibacterial and immunotropic effects of isoliquiritigenin in order to find new drugs for the treatment of staphylococcal infection.
Pharmacy & Pharmacology. 2021;9(2):139-148
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Spasov A.A., Smirnova L.A., Grechko O.Y., Eliseeva N.V., Lifanova Y.V., Rashchenko A.I., Zhukovskaya O.N., Morkovnik A.S., Anisimova V.A.


The aim of the study is the investigation of the pharmacokinetic properties of the RU-1205 compound, with previously identified kappa-agonistic and analgesic effects, at a single oral administration, as well as comparison of the relationship between its pharmacokinetic and analgesic properties.Materials and methods. Pharmacokinetic parameters of RU-1205 after the oral administration at the dose of 50 mg / kg were investigated using the method of High Performance Liquid Chromatography with determination of the concentration of the compound according to the previously constructed calibration schedule. The indices of the area under the pharmacokinetic curve, clearance, half-life, residence time of the drug molecule in the body, a total (apparent) volume of distribution, as well as the indicator of absolute bioavailability, were calculated. The tissue distribution and excretion of RU-1205 were studied.Potential metabolites of RU-1205 were predicted using the PALLAS 3.00 program. The study of the analgesic activity was carried out on a model of central somatogenic pain with electricalstimulation, with the dynamics assessment of the voltage amplitude of the corresponding reaction of the "tail-flick" reflex.Results. The compound under study is rapidly adsorbed from the gastrointestinal tract, reaching a maximum concentration by the end of the first hour of the study, and is determined in plasma within 12 hours. Its half-life is 17.7 hours. The absolute oral bioavailability is 37.3%. It was found out that the compound is withdrawn within 3-4 days. The main route of excretion is extrarenal. Biotransformation of a substance probably proceeds mainly with the formation of oxidized forms of the initial molecule by reactions of the first phase of metabolic transformation. The analgesic effect is long-lasting: it starts after 15 minutes and lasts for 12 hours with flattening of the curve by the 8th hour.Conclusion. When administered orally, the test substance undergoes a long process of elimination, has the greatest tropism for the elimination organs and undergoes active biotransformation processes in the body of animals. As a result of it, active metabolic products with an analgesic activity are, possibly, formed.
Pharmacy & Pharmacology. 2021;9(2):149-160
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Oganesyan E.T., Shatokhin S.S.


The quantum-chemical parameters of 52 derivatives related to flavanones, flavanonoles, flavones and flavonoles with a phloroglucinic type of the A ring and containing electron-donating substituents in the B ring were studied.The aim is the analysis of the dynamics of changes in the electron density, bond numbers, free valence indices and unsaturation indices on carbon atoms C-7 → C-8 of the vinyl group of the main conjugation chain in relation to the position and number of substituents in the “B” ring and the type of the pharmacological activity.Materials and methods. The quantum-chemical parameters of the 4 analyzed groups of the compounds, have been calculated by the semi-empirical method PM7 (WinMopac 2016 program) on the workstation with an Intel Xeon E5-1620 3.5 GHz processor, 20 GB of RAM.Results and discussion. When comparing the quantum chemical parameters of the analyzed compounds, it was established that when the C-7 → C-8 multiple bond is formed, the free valency and unsaturation indices increase on both carbon atoms of the vinylene group in flavones and flavonols compared to the corresponding flavanones and flavanonols. This is explained by the fact that the value of the bond numbers Nµ on these atoms, on the contrary, decreases (Fµ = 4.732-Nµ). The transition from flavanone to flavone is accompanied by the formation of a vinyl group C-7 → C-8, and therefore both atoms from the sp3-hybridized state go into the sp2-state. The consequence of this transformation is a change in the electronegativity value and an increase in the unsaturation index of C-7 and C-8 atoms: C sp3 = 2.5; Csp2 = 2.8. At the same time, the transition from flavanone to flavone leads to the formation of a conjugated system with the participation of π-electrons of the aromatic system “B”, C-7, C-8 atoms and the carbonyl group, which is commonly called the “main conjugation chain”. These structural changes, namely, the transition from a less oxidized flavanone to a more oxidized flavone, contribute to a decrease in the electron density on C-7 and C-8 atoms, and an increase in the total unsaturation of the molecules in general. Mulliken charges on C-7 of all groups of compounds are characterized by a positive value. As for the carbon atoms of the B fragment, the following features are revealed here: in the presence of one substituent -OH or -OCH3 on the carbon atom to which the substituent is bounded, the Mulliken charge is positive; if there are two substituents in the B ring -OH or -OCH3, as well as two -OCH3 groups, then the carbon atoms bonded to the indicated substituents also have a positive Mulliken charge; in the case of trihydroxy substituted in the C-2, C-3 and C-4 B ring, all three carbon atoms are characterized by a positive Mulliken charge; if there are methoxy groups in positions C-2, C-3 and C-4, then the positive Mulliken charge is concentrated only on C-2 and C-4 atoms, and on C-3 atom this charge has a negative value.Conclusion. The above data on the quantum-chemical parameters of the main conjugation chain indicate that the transition of C-7 and C-8 atoms to the sp2-hybrid state, leads to a decrease in the electron density and a decrease in the bond numbers, with a simultaneous increase in the indices of unsaturation and free valence on these atoms. Thus, the trigger mechanism of the anti-radical activity, primarily with respect to the HO • radical, is determined by the fact that this particle, electrophilic in its properties, will attach in the C-8 atom during an initial attack.
Pharmacy & Pharmacology. 2021;9(2):161-169
pages 161-169 views

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