Vol 8, No 2 (2020)


Antitrombotic activity of a new benzimidazole derivative with a spatially difficult phenolic substitute in its structure

Spasov A.A., Kucheryavenko A.F., Gaidukova K.A., Chernikov M.V., Zhukovskaya O.N.


The aim of the study was to investigate antithrombogenic properties of compound RU-1144 with previously identified pronounced antiplatelet and antioxidant activities. The thrombosis induced by Ferric chloride (FeCl3) was carried out in rats’ carotid artery, in comparison with the known antiaggregant drugs – acetylsalicylic acid (ASA) and clopidogrel, as well as with the antioxidant preparation – ethylmethylhydroxypyridine succinate (EMHPS).

Materials and methods. The antithrombotic activity of compound RU-1144 was studied on the model of the rats with carotid artery thrombosis, induced by the application of 50% ferric chloride (FeCl3), and the Global Thrombosis Test model (the Görög Thrombosis Test). The evaluation of this type of activity was carried out by prolonging the time of a blood clot formation. The studies of the compound RU-1144 effect on the bleeding time parameter were performed in mice. Acetylsalicylic acid, clopidogrel and EMHPS were used as reference drugs.

Results. The antithrombotic effect of the RU-1144 substance revealed in the model of arterial thrombosis induced by the application of ferric chloride (FeCl3), exceeded that of both acetylsalicylic acid and clopidogrel by 3.5 times and that of EMHPS by 2.9 times. In the model of the in vitro Global Thrombosis Test (the Görög Thrombosis Test), compound RU-1144 reduced the thrombogenic potential of the blood equally with acetylsalicylic acid and clopidogrel. The assessment of “the bleeding time”, caused by the RU-1144 substance, showed that the prolongation of bleeding was twice as less pronounced than that caused by ASA and clopidogrel.

Conclusion. The performed studies demonstrated a pronounced antithrombotic activity of compound RU-1144, which exceeded that of acetylsalicylic acid, clopidogrel and EMHPS, while the ability to prolong the bleeding time was reliably lower than that of reference drugs.

Pharmacy & Pharmacology. 2020;8(2):78-85
pages 78-85 views

Complex biostimulation of intrapleural adhesiogenesis in thoracal surgery

Kalashnikov A.V., Vorobiev A.A., Kalashnikova S.A., Salimov D.S.


The aim of the study is to determine the effectiveness of the use of platelet enriched plasma in the complex treatment of chest trauma and chronic pleural empyema.

Materials and methods. The work was performed on 450 male rats, simulated with chest trauma (n=180) and chronic pleural empyema (n=270). In the experimental groups, biostimulation of adhesiogenesis as an intrapleural injection of 1 ml of platelet-enriched plasma was carried out; in the comparison group; the animals with pleural empyema were injected with 1 ml of doxycycline solution; in the negative control groups, the treatment was not carried out at all. Withdrawal from the experiment took place on the 10th, 20th, 30th days. The samples of intrapleural adhesions were fixed in 10% formalin, followed by histological tracing and preparation of micropreparations, staining with hematoxylin and eosin. The morphometric study included determination of the volume fraction (VF) of collagen and reticular fibers; fibrin; inflammatory cells; blood-stream (%).

Results. An intrapleural administration of platelet-rich plasma is an effective way to stabilize the rib cage in chest injuries, and to eliminate residual cavities in chronic pleural empyema. When assessing the severity of the adhesions in chest trauma, it was found out that adhesions are most often visualized at the sites of rib fractures (from 13.3 to 40%). In pleural empyema, during the entire process of observation, the VF of collagen fibers forming adhesions was higher in the group with biological stimulation of adhesiogenesis than in the NCpe group and in the CG. In the PRP group, already at the initial stages of the experiment, this indicator was significantly lower than in the NC and CG (p<0.05).

Conclusion. Based on the data obtained, the effectiveness of the use of platelet-enriched plasma in thoracic surgery for the biological potentiation of adhesiogenesis has been proved in experimental chest injuries and chronic pleural empyema.

Pharmacy & Pharmacology. 2020;8(2):86-99
pages 86-99 views

study of antiatherosclerotic and endothelioprotective activity of peptide agonists of EPOR/CD131 heteroreceptor

Puchenkova O.A., Nadezhdin S.V., Soldatov V.O., Zhuchenko M.A., Korshunova D.S., Kubekina M.V., Korshunov E.N., Korokina L.V., Golubinskaya P.A., Kulikov A.L., Gureev V.V., Pokrovskiy V.V., Patrakhanov E.A., Lebedev P.R., Denisyuk T.A., Belyaeva V.S., Movchan E.A., Lepetukha E.I., Pokrovskiy M.V.


Introduction. The drugs affecting a mitochondrial dysfunction, oxidative stresses, apoptosis and inflammation of the vascular wall, have a high potential for the prevention and treatment of atherosclerotic lesions. In this regard, the use of EPOR/CD131 heteroreceptor agonists which have a similar spectrum of pharmacological effects, is one of the promising strategies in the treatment of cardiovascular diseases.

Materials and Methods. The study was carried out on 68 C57Bl/6J male mice. Atherosclerosis was simulated in transgenic animals with an endotheliospecific knockdown of the Polg gene by simulating a balloon injury and keeping on a Western diet. Then, the studied drugs were injected once every 3 days at the dose of 20 μg/kg for 27 days. On the 28-th day, the animals were euthanized and the area of atherosclerotic plaques was assessed. The gene expression associated with the processes of inflammation, antioxidant protection, apoptosis, and angiogenesis was also determined in the aortic tissues. In addition, the endothelium protective effect of peptides on primary cultures of endothelial cells of wild and transgenic Polg-D257A mice was studied.

Results. No statistically significant effect of drugs on the area of lipid infiltration have been found. However, the studied peptides have significantly reduced the expression of proinflammatory genes (iNos, Icam1, Vcam1, Sele, Il6, Tnfa), the genes associated with angiogenesis (Vegfa, Kdr, and Hif1a), the expression of proapoptic factors; they decreased the Bax/Bcl-2 ratio by more than 1.5 times. In addition, when supplemented with H2O2 in vitro, peptides dose-dependently increased endothelial cell survival.

Conclusion. The erythropoietin-based peptides can be used to improve the functional state of the vascular wall against the background of atherosclerotic lesions and have a depressing effect on pathobiological processes associated with a mitochondrial dysfunction. In addition, the studied peptides have a significant endothelial protective effect in the induction of oxidative stress in vitro.

Pharmacy & Pharmacology. 2020;8(2):100-111
pages 100-111 views

Using quantum-chemical parameters for predicting anti-radical (HO∙) activity of related structures containing a cinnamoyl fragment II. derivatives of 2’,4’-dihydroxychalcone, flavanone and flavone, containing a hydroxy group in position 7

Oganesyan E.T., Shatokhin S.S.


42 derivatives of 2’,4’-dihydroxychalcone, flavanone and flavone, containing the hydroxy group in position 7 (ring “A”), as well as substituents in the ring “B”, have been studied.

The aim is to study the quantum-chemical parameters of 2’,4’-dihydroxychalcone, flavanone and flavone derivatives containing a hydroxy group in position 7, in order to identify the effect of substituents on Mulliken charges (a.e) in the aromatic core “A”, bond numbers (Nµ), the unsaturation index (IUA) and the electron density of the carbon atoms of the cinnamoyl fragment.

Materials and methods. The listed above parameters 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. The analysis of the values of quantum-chemical parameters, as well as their comparison with the corresponding indicators presented in Report I, revealed a number of important features associated with the influence of the hydroxy group in position 7 (ring “A”) on the studied quantum-chemical parameters of molecules. It has been established that the hydroxy group in the ring “A” does not significantly affect the Mulliken charge and the electron density of the carbon atoms of the propenone unit C-7→C-8→C-9. On atom C-9 (carbonyl carbon), the Mulliken charge always has a positive value, and the electron density is about 3.4670-3.4840 for all three groups of compounds. The transition from 2’,4’-dihydroxychalcone to flavanone and flavone by the formation of the pyrone heterocycle, is accompanied by an increase in the negative charge on C-8, which can be explained by the involvement of the oxygen heteroatom in the transmission of electronic effects. The hydroxy group in the ring “A”, has practically no effect on the charge and electron density of atoms. An analysis of the values of bond numbers and unsaturation indices suggests that atoms C-1 of 2’,4’-dihydroxychalcone and 7-hydroxyflavanone derivatives, are characterized by the lowest Nµ value; the lowest bond numbers are characteristic for atom C-8 derivatives of 7-hydroxyflavone. Consequently, the primary attack of the HO·radical will be directed at C-1 (in chalcones and flavanones) and at C-8 in flavones.

Conclusion. The performed quantum-chemical calculations make it possible to analyze the effect on the main quantum-chemical parameters of the molecule, which can be useful in predicting the biological activity of flavanoid compounds due to their antiradical effect on reactive oxygen intermediate species (ROIs).

Pharmacy & Pharmacology. 2020;8(2):112-123
pages 112-123 views

Films in Russian medicine and cosmetology: development history, classification, technology

Kishchenko V.M., Vernikovsky V.V., Privalov I.M., Shevchenko A.M.


Since the moment of their appearance in the second half of the 20th century, application forms have attracted the attention of the specialists involved in the skin application of pharmacologically active agents. Herewith, both localized exposure to the external integuments and the possibility of achieving a systemic effect, are of interest. The range of products used in modern films, is also wide – from pharmaceutical substances to biologically active components of cosmetics.

The aim of the present work is to study the current state of research in the field of the creation and improvement of medicinal and cosmeceutical films.

Materials and methods. The study was conducted on the base of patent information (fips.ru, findpatent.ru) and information and search databases – the State register of medicines (grls.rosminzdrav.ru) and the data from the Federal accreditation service (www.fsa.gov.ru), as well as scientific libraries (Google Scholar, eLIBRARY, PubMed) and reference literature.

Results. Native and foreign medicinal films have longer than a 50-year history of their existence in the pharmaceutical market. Modern scientists’ interest in this application form, does not fade away due to a great number of its positive characteristics. In addition to pharmaceutical applications, films are widely used in cosmetics in the form of masks applied to the skin. Biologically active substances are widely used in cosmetics which, in recent years, has led to the emergence of a group of cosmeceutical products that combine medical and cosmetic films. The article also discusses film manufacturing technology, active substances, as well as polymers used for medicinal and cosmetic films presented in the Russian market.

Conclusion. The analysis of the literature data makes it possible to conclude that the development of films is promising in both medicine and cosmeceuticals.

Pharmacy & Pharmacology. 2020;8(2):124-132
pages 124-132 views

Chemical constituents of Geum rivale L. and their biological activity

Orlova A.A., Povydysh M.N.


The aim of the study is to review the literature data on the chemical constituents of arial and underground parts of Geum rivale L. (Rosaceae) and the pharmacological activity of its extracts and individual compounds.

Materials and methods. The study was carried out using Internet resources (Google Scholar, PubMed) and library databases (e-Library, Scopus, Web of Science). The main research methods were a review and analysis of the literature data on the topic for the period from 1958 up to the present.

Results. For the period from 1958 up to the present more than 80 components in the arial and underground parts of G. rivale have been identified. Among them there were components of the essential oil, phenolic acids and coumarins, aglycones of flavonoids, including luteolin, apigenin, quercetin and kaempferol, as well as a number of their glycosides and glucuronides, ellagitannins (hemin A, B, C, D, pedunculagin, stachiurin/casuarinin, tellimagrandin I). Some aspects of the pharmacological activity of total extracts and individual secondary metabolites of G. rivale have been studied, anti-inflammatory, antioxidant, antimicrobial, antiviral activities have been experimentally confirmed.

Conclusion. The analysis of the literature data showed that a further study of the composition of metabolites of G. rivale and their pharmacological activity is an urgent task, the solution of which will expand the range of use of this plant in medical practice and consider G. rivale as a promising source of pharmaceutical substances for the creation of new drugs and biologically active additives.

Pharmacy & Pharmacology. 2020;8(2):133-146
pages 133-146 views

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