Current issues in pharmacy and medicine: science and practice

Journal Information
ISSN / EISSN : 2306-8094 / 2409-2932
Published by: Zaporozhye State Medical University (10.14739)
Total articles ≅ 414
Current Coverage
DOAJ
Archived in
SHERPA/ROMEO
Filter:

Latest articles in this journal

A. V. Khilkovets
Current issues in pharmacy and medicine: science and practice, Volume 14, pp 152-156; https://doi.org/10.14739/2409-2932.2021.2.232334

Abstract:
Heterocyclic compounds are one of the most important branches of modern organic chemistry and are widely used in medicine, pharmacy, agriculture, and in the production of new materials. One of these compounds is 1,2,4-triazole, which has attracted the attention of scientists around the world for many years. The aim of the work is to synthesize new derivatives of 5-(thiophene-3-ylmethyl)-4R-1,2,4-triazole-3-thiols and study their physical-chemical properties, conducting primary pharmacological screening. Materials and methods. Organic synthesis classical methods were used in the study, as well as a complex of physical-chemical analysis methods (1H NMR spectroscopy, elemental analysis, Elisa and chromato-mass spectral studies) were done. Prediction of pharmacological activity was carried out by using the PASS online computer program. Results. Two initial compounds were obtained: 5-(thiophene-3-ylmethyl)-4phenyl-1,2,4-triazole-3-thiol and 5-(thiophene-3-ylmethyl)-4H-1,2,4-triazole-3-thiol. During their further chemical transformation, a number of new corresponding alkyl derivatives were obtained. The structure of the synthesized compounds was confirmed using modern physical-chemical methods of analysis. Based on the results of pharmacological screening, the high activity of the obtained compounds can be predicted. Conclusions. 5-(thiophene-3-ylmethyl)-4H-1,2,4-triazole-3-thiol, 5-(thiophene-3-ylmethyl)-4-phenyl-1,2,4-triazole-3-thiol and a number of their alkyl derivatives were synthesized. The structure and individuality were proved thanks to modern physical and chemical methods of analysis. Having analyzed the results of primary pharmacological screening of a number of obtained compounds, some of them were selected for further study.
A. H. Halstyan, A. S. Bushuiev
Current issues in pharmacy and medicine: science and practice, Volume 14, pp 157-161; https://doi.org/10.14739/2409-2932.2021.2.230051

Abstract:
4-Nitroacetophenone is an important intermediate for the manufacture of broad-spectrum antibiotics, in particular chloramphenicol. Existing methods of ketone synthesis are imperfect. The disadvantage of the simplest of them (the oxidation of 4-nitroethylbenzene by oxygen at atmospheric pressure and temperature of 135 °C, in the presence of manganese oxide) is the low yield and the need for the process in a heterogeneous environment. Therefore, the development of affordable and inexpensive ways to obtain 4-nitroacetophenone is an actual task. The aim of the work is to investigate the products and kinetics of the reaction of catalytic oxidation of 4-nitroethylbenzene by ozone in acetic acid and to develop a new low-temperature synthesis of 4-nitroacetophenone. Materials and methods. The experiments were used 4-nitroethylbenzene, 4-nitroacetophenone and 1-(4-nitrophenyl)ethanol by company Acros organics qualification “puriss.”; manganese (II) acetate qualification “puriss.”; as a solvent – glacial acetic acid by company Sigma qualification “puriss.”. A spectrophotometric method was used to continuously monitor the current concentration of ozone in the gas phase. A Teflon flow cell with quartz windows was installed in the measuring chamber of the SF-46 LOMO spectrophotometer, which allowed the measurement of the optical density of the gas flow in the UV region. The concentration of ozone at the inlet and outlet of the reactor was determined by recording the results on the potentiometer KSP-4 in the form of an ozonogram when passing ozone-containing gas through a cuvette at a wavelength of a monochromatic light source 254–256 nm. The quantitative content of the reaction mixture was performed using gas-liquid chromatography, calculations of the concentration of components were performed by the method of internal standard. Results. The products and kinetics of the reaction of ozone with 4-nitro-ethylbenzene in the presence of a catalyst – manganese (II) acetate were studied. It was found that at a temperature of 20 °C the oxidation process proceeds mainly along the side chain, while the yield of 4-nitroacetophenone reaches 98.5 %, also the system identified trace amounts of 1-(4-nitrophenyl)ethanol. This fact is explained by the fact that ozone under catalysis conditions preferably reacts not with the substrate, but with Mn (II) with the formation of the active form of Mn (IV) which, in turn, is reduced by reaction with 4-nitroethylbenzene, and thus initiates oxidation of the substrate. on the side chain. Conclusions. Catalytic oxidation of 4-nitroethylbenzene by ozone in acetic acid solution proceeds mainly along the side chain to form 4-nitroacetophenone with a yield of 98.5 %. The optimum reaction temperature is 20–30 °C, as its increase deepens the oxidation process and the ketone begins to be converted into 4-nitrobenzoic acid.
, O. I. Panasenko
Current issues in pharmacy and medicine: science and practice, Volume 14, pp 173-178; https://doi.org/10.14739/2409-2932.2021.2.234565

Abstract:
The relevance of the study of 1,2,4-triazole derivatives with pyrimidine fragment is due to the synthesis of potential broad-spectrum antibacterial drugs, low molecular weight inducers of interferon, and antitumor agents, search for molecular descriptors of their structure, important for establishing patterns “structure – biological activity”. The aim of the work is a computer search for the antibacterial action of new hybrids of 1,2,4-triazole-3(2H)-thiol with a pyrimidine fragment in relation to 5 test cultures, to establish the dependence of “structure – action”. Materials and methods. For an in-depth study of the antibacterial activity of derivatives of 1,2,4-triazole-3(2H)-thiol hybrids with a pyrimidine fragment, 4 test cultures of museum strains of gram-positive, gram-negative bacteria and one species of fungi were selected. In silico studies were performed using regression and classification QSAR models. Results. Derivatives of 1,2,4-triazole-3(2H)-thiol hybrids with a pyrimidine moiety showed high antibacterial activity against gram-negative microorganisms (E. coli, P. aeruginosa). The obtained experimental results allowed to establish not only the role of the main structural features of the compounds in the manifestation of antimicrobial properties, but also to evaluate the effectiveness of the created classification and regression QSAR models. Based on the presented parameters for individual predictive QSAR models, it is possible to conclude about the effectiveness, stability and feasibility of using these models to search for new S-derivatives (1,2,4-triazole-3(2H)-yl)methyl)thiopyrimidines as promising antimicrobial agents. Conclusions. It was found that the studied derivatives of hybrids of 1,2,4-triazole-3(2H)-thiol with a pyrimidine fragment showed high antibacterial activity against gram-negative microorganisms. The developed QSAR classification models based on the percentage of correctly predicted compounds (70 %) are the most effective in comparison with regression (50 %) for the search for new antimicrobial agents in a number of derivatives of hybrids 1,2,4 triazole-3(2H)-thiol with pyrimidine fragment.
Current issues in pharmacy and medicine: science and practice, Volume 14, pp 232-238; https://doi.org/10.14739/2409-2932.2021.2.232053

Abstract:
In order to save resource of active pharmaceutical ingredients and excipients, in the early stages of research, when planning an experiment, it is advisable to use data of the predicted and experimental physicochemical properties stored in different aggregation databases. The information found will reduce the time for composition development and for technology processing. However, the variety of active compounds characteristics and excipients is not always reflected in these services. Recently, machine learning models have been widely used in various scientific fields; they allow to obtain predictions with high reliability. Given the above, it is relevant and promising to develop models of machine learning to predict the presence of pharmaceutical incompatibilities in the formulation of nasal dosage forms. The aim of the study is to develop models of machine learning for in silico forecast of the rational composition of nasal dosage forms with cerebroprotective action. Materials and methods. A dataset, containing data on compounds (active and auxiliary) and characteristics on the presence or absence of interaction (pharmaceutical incompatibility), was used as material. Training datasets were filled by content analysis of PubMed library data (pubmed.ncbi.nlm.nih.gov) manually, by keywords “pharmaceutical incompatibilities”, “physico-chemical compatibility”, “incompatible excipients”) for the last 10 years. The resulting dataset comprises 1185 lines. The methods employed were a set of methods for binary classification of machine learning (pycaret.org) using the programming language Python 3.8 (python.org) in the package management environment Miniconda (conda.io). Pipeline programming was performed using Jupyter notebook package (jupyter.org). The generation of MACCS (Molecular ACCess System keys) in the training dataset was performed using RDKit package (rdkit.org). Specifications of the simplified representation of molecules in the input line (SMILES), in automatic mode, were searched using PubChem service (pubchem.ncbi.nlm.nih.gov). Results. The obtained data allowed to choose two perspective models of machine learning of binary classification, whose quality was checked on a dataset for verification. Statistical evaluations of the selected models indicate a high probability of in silico prognosis for the presence or absence of pharmaceutical incompatibilities in the development of nasal formulations of cerebroprotective dosage forms. They are posted on the web server of the expert system ExpSys Nasalia (nasalia.zsmu.zp.ua) in the calculations section. Conclusions. As a result of our research, we have developed machine learning models for in silico prediction of the rational composition of nasal dosage forms with cerebroprotective action. Confirmation of the quality of the pharmaceutical incompatibilities prediction, using the developed models, is checked on a dataset for check. The statistical indicators of the tree_blender (AUC 0.9521, F1 0.9747, MCC 0.9094) and boost_blender (AUC 0.9593, F1 0.9821, MCC 0.9352) models were obtained. The use of machine learning models in pharmaceutical development will contribute to resource conservation and optimization of the composition of the formulation.
A. A. Safonov, I. S. Nosulenko
Current issues in pharmacy and medicine: science and practice, Volume 14, pp 162-166; https://doi.org/10.14739/2409-2932.2021.2.230129

Abstract:
The process of studying free radicals began in the middle of the last century (the free radical theory of aging in 1956). Multiple studies have revealed the effect of free radicals on the cells of the body and the development of various diseases, such as diabetes, autoimmune diseases, diseases of the nervous system, and others. As a result, the term antioxidant has emerged, compounds that reduce and prevent the effects of free radicals. Most of the newly synthesized substances are studied for their antiradical properties. 1,2,4-Triazole derivatives are no exception, which has already proven themselves as biologically active compounds. The aim of this work was the investigation antiradical activity among 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives. Materials and methods. Previously synthesized 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives were used as test compounds. The research of antiradical activity was based on the interaction between 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives and 2,2-diphenyl-1-picrylhydrazyl (DPPH) in vitro. DPPH is a stable free radical. The color of its alcoholic solutions were intense purple (λmax = 517 nm). When DPPH interacted with compounds that were capable of scavenging free radicals, it produced products. These products are yellow in color and do not absorb light of the aforementioned wavelength. The study was carried out according to the method. Results. The antiradical activity of 10 new 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives was studied. Most of the test compounds show antiradical activity against DPPH. Compound 1 was the most active at a concentration of 1 × 10-3 M and the antiradical effect was close to ascorbic acid. Conclusions. The most active compound is 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol, which in a concentration of 1 × 10-3 M has an antiradical effect in 88.89 %. When reducing the concentration to 1 × 10-4 M, also reduces the antiradical activity to 53.78 %. Some conclusions are drawn regarding the “structure – effect” dependence between 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives: – the introduction of 4-fluorobenzylidene radical (compound 2) into the 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol molecule results in a slight decrease in activity; – the introduction of 2-hydroxybenzylidene radical (compound 3) into initial molecule results a high antiradical effect, which hardly changes with decreasing concentration; – transformation to 2-((5-(thiophen-2-ylmethyl)-4-((R)amino)-4H-1,2,4-triazol-3-yl)thio)acetic acid has almost no effect on antiradical activity, except for compound 9 (the antiradical effect is reduse).
O. H. Aleksieiev
Current issues in pharmacy and medicine: science and practice, Volume 14, pp 251-258; https://doi.org/10.14739/2409-2932.2021.2.234301

Abstract:
The aim to characterize civil liability as a component of legal liability in pharmacy. Materials and methods. During the research, the methods of analysis, synthesis, and legal comparison were used. National civil legislation, as well as general theoretical approaches and points of view to the issues of civil liability in the pharmaceutical healthcare sector were used as research material. Results. The sphere of circulation of medicines is a multifaceted complex of legal relations regulated by the norms of various branches of law. At the same time, their generalizing feature is the focus on providing the population with affordable, safe and high-quality medicines. Establishing the rights of citizens at the legislative level, the legislator always necessarily provides for mechanisms of protection against violation of these rights. One of the most effective mechanisms is legal liability. Since the above citizens' rights are civil rights, it seems relevant to investigate the essence and content of civil liability in the pharmaceutical healthcare sector. Pacta sunt servanda is a principle of international law, according to which treaties are binding and must be executed in good faith. Unlike contractual liability, delict liability occurs in cases where the violator does not have a contractual relationship with the offended party. Conclusions. Civil liability is one of the most effective measures to ensure the constitutional right of citizens to accessible. safe and quality medicines. Determination of the legal status of a pharmaceutical worker as one of the central figures in healthcare is necessary for the correct determination of the type of civil liability
V. M. Odyntsova, V. H. Korniievska, M. M. Maletskyi, Yu. I. Korniievskyi
Current issues in pharmacy and medicine: science and practice, Volume 14, pp 200-210; https://doi.org/10.14739/2409-2932.2021.2.234723

Abstract:
The family Apiaceae includes 474 genera and 3992–4050 species that are distributed around the globe. Of all the variety of species, our attention was drawn to the raw material of anise – Anisum vulgare Gaertrn.; fennel – Foeniculum vulgare Mill., which contains derivatives of phenylpropane; coriander – Coriandrum sativum L.; dill – Anethum graveolens L.; caraway – Carum carvi L., which is rich in monoterpenoid derivatives. These plants are widely used in medical practice and known to have antimicrobial, antispasmodic, expectorant, antihypertensive, diuretic, choleretic, carminative effects. This versatility is due to the presence of different groups of biologically active substances in the raw materials of plants. The aim of the research is to determine, by means of gas chromatography, a component composition of fruit tinctures of Anisum vulgare Gaertrn., Foeniculum vulgare Mill., Coriandrum sativum L. Anethum graveolens L. and Carum carvi L. Materials and methods. Tinctures were prepared in ratio 1:5 (extractant – 70 % ethyl alcohol) from anise, fennel, coriander, dill, and caraway fruits, which had been harvested in the experimental field of Zaporizhzhia State Medical University in August 2019. Qualitative and quantitative determination of the active compounds was performed using an Agilent 7890B gas chromatograph with a 5977B mass spectrometric detector. The NIST14 mass spectrum library was used to identify the components. Results. It has been revealed that the tinctures of Anisum vulgare Gaertrn., Foeniculum vulgare Mill., Coriandrum sativum L. Anethum graveolens L., and Carum carvi L. differ in qualitative and quantitative composition of components of chromato-mass spectrometry. Tinctures of Anethum fructus contain 28 components, among which 8.028 RT (-)-Carvone (52.63 %) and 4.861 RT D-Limonene (17.74 %) prevail. Tinctures of Coriandrum fructus contain 37 components with the highest content of 11,016 RT Benzene, 1-(1,5-dimethyl-4-hexenyl)-4-methyl (20.7 %) and 19.372 RT 1-(4-hydroxy-3-methoxyphenyl)dec-4-en-3-one (8.57 %). In the tincture of Carum carvi L., which contains 33 components, the following may be considered predominant: 7.988 RT Benzaldehyde, 4-(1-methylethyl) (47.37 %) and 19,311 RT undetermined compound (5.88 %). The tincture of Anisum fructus has 22 components, with the highest content of 8.531 RT Estragole (60.32 %) and 4.852 RT D-Limonene (5.15 %); Foeniculum fructus tincture contains 52 components, among which 5.745 RT Fenchone (15.39 %) and 8.5 RT Anethole (11.37 %) prevail. Conclusions. The results of gas chromatography of fruits of the Apiaceae family significantly expand the information about the chemical composition of raw materials and indicate the prospects for use in pharmaceutical and medical practice. Analyzing the results of gas chromatography, it has been found that tinctures of fruits of the Apiaceae family differ in qualitative and quantitative composition of components. Tinctures of Foeniculum fructus contain 52 components, Coriandrum fructus – 37 components, Carum carvi L. contain 33 components, Anethum fructus – 28 components, Anisum fructus – 22 components. The obtained experimental data can be used to create regulatory documentation for a particular type of medicinal plant raw materials.
V. А. Lysenko
Current issues in pharmacy and medicine: science and practice, Volume 14, pp 226-231; https://doi.org/10.14739/2409-2932.2021.2.232175

Abstract:
Treatment of chronic heart failure (CHF) is very controversial. The issue of optimal doses of beta-blockers, ACE inhibitors, aldosterone receptor antagonists, statins in patients with CHF has not been conclusively addressed. Achieving the maximum tolerated doses of drugs, though related to reduced mortality, but is accompanied by an increase in adverse drug reactions. The aim. To present and discuss our own clinical and scientific data concerning the role of beta-blockers and inhibitors of the renin-angiotensin aldosterone system, diuretics, statins in the treatment of CHF patients and optimization of dosage schemes. Material and methods. The study included 88 patients with CHF of ischemic origin, with sinus rhythm, stage II AB, NYHA FC II–IV, 58 – with reduced LV EF (HFrEF) and 30 – with preserved LV EF (HFpEF). The mean age of patients was 69.18 ± 9.97 years, men 52 % (n = 46). The median follow-up of the CHF patients was 396 days, the maximum number of follow-up days was 1302. During the observation period, 14 endpoints were registered, which accounted for 15.91 % of events: 7 deaths (8.0 %), 2 strokes (2.3 %), 2 cases of acute coronary syndrome (2.3 %), 3 progressive heart failure cases (3.4 %). Kaplan–Mayer curves were drawn to assess survival rate, and the significance of difference between groups was calculated by the criteria of Gehan–Wilcoxon, Cox–Mantel and log-rank test. Risk factors were determined, and prognostic uni- and multi-variant Cox proportional hazards regression models were used. The cut-off values of quantitative risk factors were obtained by ROC analysis. Results. The increase in the relative risk of adverse cardiovascular events in the CHF patients regardless of LV EF was associated with a daily carvedilol dose of more than 25 mg (HR = 1.05; 95 % CI 1.009–1.093; P = 0.0171); eplerenone – more than 12.5 mg (HR = 1.073; 95 % CI 1.005–1.144; P = 0.034), torasemide – more than 5 mg (HR = 1.13; 95 % CI 1.021–1.255; P = 0.019); rosuvastatin – more than 10 mg (HR = 1.107; 95 % CI 1.007–1.203; P = 0.035), and the trend in using atorvastatin at a dose of less than 10 mg (HR = 1.05; 95 % CI 0.951–1.165; P = 0.327). The use of ramipril in a daily dose of less than 2.5 mg was accompanied by a trend towards the 22 % reduced relative risk of adverse cardiovascular events (HR = 0.78; 95 % CI 0.384–1.580; P = 0.491). Conclusions. Positive treatment outcomes in the CHF patients, regardless of the phenotype, were associated with low daily doses of ramipril (<2.5 mg), eplerenone/spironolactone (<12.5 mg), torasemide (<5.0 mg), rosuvastatin (10.0 mg).
O. I. Panasenko, В. І. Мозуль, O. M. Denysenko, І. І. Аксьонова, T. V. Oberemko
Current issues in pharmacy and medicine: science and practice, Volume 14, pp 179-184; https://doi.org/10.14739/2409-2932.2021.2.233708

Abstract:
The aim of the work was chromato-mass-spectroscopic research of chemical composition of Elaeagnus angustifolia L. fruits and leaves and identifying further prospects for the use of this plant in medicine. Materials and methods. Raw materials of Elaeagnus angustifolia L. were selected as objects of study. The tincture was obtained by maceration and the raw material was extracted with methyl alcohol at room temperature for 10 days according to the method of making tinctures. The study of the chemical composition of Elaeagnus angustifolia L. was carried out using gas chromatograph Agilent 7890B GC System (Agilent, Santa Clara, CA, USA) with mass spectrometric detector Agilent 5977 BGC/MSD (Agilent, Santa Clara, CA, USA) and chromatographic column DB-5ms (30 m × 250 mkm × 0,25 mkm). Results. 23 compounds (1 in the isomeric state) in fruits and 20 compounds (2 in the isomeric state) in the leaf of Elaeagnus angustifolia L. were identified. The main components of fruits were sitosterol (phytosterols) – 12.53 %, propyl acetate (esters of carboxylic acids) – 12.60 %, chamazulene (terpenes) – 11.97 % and palmitic acid (fatty acids) – 8.28 %. The main component of leaves were sitosterol (phytosterols) – 17.57 %, 1-(2-hydroxy-5-methylphenyl)-ethanone (ketone) – 8.35 %, phytol (terpenes) – 6.10 %. It is known from the literature that chamazulene has antioxidant, antinociceptive, cytotoxic activity. Sitosterol has anti-inflammatory and antidiabetic activity. Hexadecanoic (palmitic) acid has antimicrobial, antidiabetic and antioxidant properties. Phytol is characterized by a wide range of biological action – antimicrobial, antinociceptive, anti-inflammatory, antioxidant and cytotoxic. Conclusions. Based on the above, the olive can be considered as a source of antimicrobial, antinociceptive, anti-inflammatory, antioxidant, antidiabetic and cytotoxic drugs.
Ya. M. Steshenko, O. V. Mazulin, N. M. Polishchuk
Current issues in pharmacy and medicine: science and practice, Volume 14, pp 211-214; https://doi.org/10.14739/2409-2932.2021.2.230049

Abstract:
The main problem of modern phytotherapy is the medicinal plants that have a sufficient raw material base and contain a large number of biologically active substances. Treatment of diseases with synthetic drugs leads to the development of resistance to pathogenic microflora and the appearance of allergic reactions. Therefore, to solve this problem, it is necessary to find new plant-based antimicrobials that are safe for long-term use and have a wide spectrum of action. The aim of the work was to study the antibacterial and fungicidal activity of the essential oil of Thymus x citriodorus (Pers.) Schreb. var. “Silver Queen”. Materials and methods. The essential oil of Thymus x citriodorus (Pers.) Schreb. var. “Silver Queen” was used for the experimental part. To test the antimicrobial and antifungal action of the essential oil, reference test strains, gram-positive and gram-negative bacteria, as well as yeast-like fungi of the genus Candida were selected. The studies were performed in vitro using the disco-diffusion method. Results. Studies have shown that the essential oil of Thymus x citriodorus (Pers.) Schreb. var. “Silver Queen” has a significant antibacterial effect against S. aureus ATCC 25923 (diameters of growth inhibition were 14.60 ± 1.52 mm) and fungicidal effect Candida albicans ATCC 885-6530 (29.30 ± 2.82 mm). Antibacterial activity of the essential oil was detected in relation to E. coli (19.60 ± 1.85 mm). It was experimentally proven that the essential oil had no bactericidal effect on the test strain of P. aeruginosa. Conclusions. It was found that the essential oil of the studied hybrid species Thymus x citriodorus (Pers.) Schreb. var. “Silver Queen” shows a significant antibacterial activity and is promising for further research.
Back to Top Top