STUDY OF BIOLOGICAL ACTIVITY OF RACEMIC AND OPTICALLY ACTIVE ESTERS OF NAPHTHENIC AND FATTY ACIDS BASED ON UNSATURATED OXYESTERS

Petrochemical products based on petroleum naphthenic acids have special properties. Esters of naphthenic acids possess practically valuable organic compounds. The aim of this work is the development of effective methods for the preparation of aromatic esters based on naphthenic and individual fatty acids which is a very promising direction in the medicine practice. The synthesis of unsaturated racemic and chiral oxyethers was carried out on the basis of the interaction of chloromethylpropargyl (allyl) esters with carbonyl compounds with the participation of metallic zinc. Also, to study the biological activity, racemic and optically active esters were synthesized based on naphthenic acids and unsaturated racemic and chiral oxyesters. As test cultures used: gram-positive (Staphylo-coccus aureus-Staphylococcus aureus), gram-negative (Pseudomonas aeruginosa – Pseu-domonas aeruginosa, Escherichia coli) bacteria, as well as yeast-like fungi of the genus Candida - Candida albicans. Analysis of the biological activity of the synthesized compounds showed that optically active bicyclo [2.2.1] hept-5-ene-2-methylol monoesters have higher antimicrobial and antifungal activity compared to their racemic analogs and drugs used in medicine.

Antibacterial and physical characteristics of silver loaded hydroxyapatite/alginate composites

The influence of silver ions on antibacterial properties and morphology of Hydroxyapatite-Ag (HА-Ag) and Hydroxyapatite-Alginate-Ag (HA-Alg-Ag) nanocomposites was studied. The microstructure and phase composition of the obtained nanocomposites were investigated by SEM, TEM, XRD, FTIR methods, and the formation of the crystalline phase of Ag3PO4 was proved. According to the results, silver ions were incorporated into the HA structure, partially replacing calcium ions. The antimicrobial activity assessment was carried out on Gram-negative (Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus) test cultures by the co-incubation and modified «agar diffusion» methods. We have demonstrated that antimicrobial and adhesive properties of both Ag-HA and HA-Alg-Ag are strongly affected by the crystal lattice structure, controlled by silver ions location. The composite materials could be of great interest in the biomedical field, including the design of coatings that prevent or lag the bacterial biofilm development.

Substantiation of safe use of disinfectant «STERIZENT»

diseases, especially a use of the disinfectants (DS), in particular, are of special relevance in order to break the mechanisms of the transmission of infectious agents. The variety of DS, presented at the modern market, allows us to choose the most appropriate ones for the purposes, conditions and methods of application. However, the effectiveness and safety of the DS both for humans and the environment are still the main choice criteria. In this regard, electrolysis preparations (anolytes) attract a special attention. Objective: We determined the bactericidal, virucidal and yeast activity of the STERISENT preparation (Israel) according to modern requirements and standards. Materials and methods: Studies of the specific activity of the DS "STERISENT" were carried out in accordance with the Order of the Ministry of Health of Ukraine No. 2024, 03.09.2020 and the European standards. The test cultures and culture media recommended by the Order No. 2024 and the standards EN 13727: 2012 + A2: 2015 [3] and DSTU EN 13624: 2019 (EN 13624: 2013, IDT) were used in the quantitative suspension method. Virucidal activity was studied in the intestinal bacteriophages T2 and MS2.Toxicological studies were carried out in the laboratory animals in accordance with modern standards. Results: A high bactericidal and yeast-killing activity of STERISENT preparation (Israel) in undiluted form was established for Escherichia coli K12 NCTC 10538 lg R >5.42, for Pseudomonas aeruginosa lg R >5.37; for Staphylococcus aureus lg R >5.34; for Candida albicans lg R >4.31at exposure of 30 s and 60 s. In the study in bacteriophages at an exposure of 30 s, the logarithms of the reduction were: T2 - >5.08, MS2 - >5.12. According to GOST 12.1.007-76,by the parameters of acute toxicity, STERIZENT preparation belongs to class 4 - low-hazardous substances when administered to the stomach and applied to the skin; at the inhalation application in saturated concentrations - to class 3. moderately dangerous substances. The preparation does not have a sensitizing effect in the recommended modes of application.

Lytic Exoenzymes of Soil Strains of Bacillus Representatives and Manifestations of their Biological Activity

Bacteria of the genus Bacillus make up a significant (8–12%) part of the soil microbiome. Manifestation of their biological activity, in particular, the antagonistic and lytic activity against other microorganisms directly depends on their exometabolites. According to the literature, such properties of soil bacteria of the genus Bacillus thus can be related to their various lytic exoenzymes. Aim. To evaluate the role of lytic exoenzymes of the studied soil bacteria strains of the genus Bacillus in the manifestation of their biological (antagonistic, lysing) activity. Methods. The antagonistic activity of bacteria strains of the genus Bacillus against phytopathogenic micromycetes was determined by the method of double culture in Petri dishes on potato-glucose agar. For qualitative analysis of the presence of extracellular enzymes, strains of bacteria of the genus Bacillus were plated on Petri dishes with solid mineral-salt medium and a suitable substrate inducer. The ratio of the diameter of substrate hydrolysis zone to the diameter of the colony was taken as the relative enzymatic activity of the culture. Bacteriolytic activity of the studied strains was determined by the change in optical density of living cells of phytopathogenic bacteria suspension at 540 nm. Results. Six strains of bacteria of the genus Bacillus were selected by the results of preliminary screening, with at least five types of lytic activity, namely proteolytic, chitinase, amylolytic, cellulase, and xylanase of different levels (low, average, high). Analysis of the antagonistic activity of the selected strains of bacteria of the genus Bacillus to the main groups of phytopathogenic bacteria (six test cultures) singled out the strain Bacillus sp. 41 for a careful study of the nature and spectrum of its antagonism. Analysis of the level of antagonistic activity of the selected Bacillus strains against the phytopathogenic micromycetes showed that the minimum decrease of antagonism (the decrease of growth inhibition zones) during the observation period (at the 3rd and 7th days) was in Bacillus sp. 41 strain. Therefore, only this strain showed a stable and relatively wide range of antagonistic activity against phytopathogens of bacterial and fungal etiology. The nature of this antagonism is probably complex and conditioned by the participation of various biochemical mechanisms, in particular, the synthesis of a complex of lytic exoenzymes. To assess the lysing activity of Bacillus strains, three strains with the highest proteolytic and cellulolytic activity of exoenzymes were taken from the six previously chosen. Only Bacillus sp.1913 strain showed high (70%) lytic activity against gram-negative polyphagous phytopathogen Pseudomonas syringae pv. syringae UCM B-1027T. Such activity of the strain did not manifest against the rest of the phytopathogenic test cultures. The high lytic activity of Bacillus sp. 1913 strain may be associated with high activity of exogenous proteases and cellulases of the lytic complex, which is quite consistent with the literature data on the lytic activity of bacteria of the genus Bacillus. Conclusions. The spectrum and activity of lytic exoenzymes of strains of the studied soil bacteria of the genus Bacillus indicate the indirect participation of these enzymes in the manifestation of biological activity (antagonistic and lytic).

Experimental investigation of peculiarities for impact of a sorption action preparation silicon dioxide on infectious agents of cholangitis

Objective. Determination of impact of combination, consisted of 3% solution of silicon dioxide and antibacterial preparations, on bacterial cultures of S. aureus, P. aeruginosa, E. coli. Materials and methods. Clean cultures of bacteria, kept in Collection of Microorganisms in Department of Microbiology and Immunology of Training–Scientific Centre «Іnstitute of Biology and Medicine» of Taras Shevchenko National University: S. aureus (Rosenbach, 1884), P. aeruginosa (Schröter, 1872; Migula, 1900), E. coli (Migula, 1895; Castellani і Chalmers, 1919) were applied. Action of antibacterial preparations cefoperazon, cefoperazon–sulbactam, ampicillin–sulbactam, amicacin, as well as enterosorbent 3% solution of silicon dioxide, was investigated. In the investigation the impact of antibacterial preparations and silicon dioxide together with antibacterial preparations on test–cultures of bacteria was studied, using broth and agarised medium of Muller–Hinton. Results. The data, obtained in the investigation, trust efficacy of combined application of 3% solution of silicon dioxide, owing sorption capacity, with antibacterial preparations in reduction or elimination of subsequent growth of bacterial test–cultures of S. aureus, P. aeruginosa, E. coli. Combination of 3% solution of silicon dioxide with ampicillin–sulbactam in dilutions 64 and 32 mg/l promotes reduction of the E. coli growth on surface of agarised medium in comparison with the investigation variant without application of 3% solution of silicon dioxide. While polyresistence of P. aeruginosa revealed, 3%solution of silicon dioxide together with cefoperazon–sulbactam in concentrations 8 and 16 mg/l and ceftazidime in concentrations 8, 16, 32, 64 mg/l guarantees bactericidal effect for this microorganism. Growth of P. aeruginosa while application of 3% solution of silicon dioxide in combination with ampicillin–sulbactam in dilutions 8, 16, 32, 64 mg/l was arrested. Application of 3% solution of silicon dioxide in combination with amicacin–sulbactam 16 mg/l inhibits the S. aureus growth, what is observed, when combination of 3% solution of silicon dioxide with amicacin in dilutions 8, 16 mg/l and cefoperazon–sulbactam in dilutions 8, 16 mg/l are exploited. Growth of the microorganism do not evolve in variants of the investigation without 3% solution of silicon dioxide, as well as with him, if amikacin is applied in concentrations 64 and 32 mg/l. Conclusion. The biliary ducts drainage in obturative jaundice of tumoral genesis and subsequent presence of drainage (internal or external) constitute the main risk factors for their colonization by multiresistant microorganisms. At the same time, the biliary ducts drainage in combination with antibioticotherapy is estimated as an urgent method for control of the infection primary focus in an acute cholangitis. Establishing of procedure for application of 3% solution of silicon dioxide in combination with certain groups of antibacterial preparations for microorganisms revealed constitute important measure for bacteriobilia prophylaxis. The further investigations conduction with wider spectrum of antibacterial preparations and 3% solution of silicon dioxide for control of clinically significant species of microorganisms is necessary and perspective.

BIOLOGICAL ACTIVITY OF N-{3-[(4-METHYLBENZENE-1- SULFONYL)IMINO]-6-OXOCYCLOHEXA-1,4-DIEN-1-YL}ARYLAMIDES AND THEIR DERIVATIVES

N-{3-[(4-Methylbenzene-1-sulfonyl)imino]-6-oxocyclohexa-1,4-dien-1-yl}arylamides and their derivatives were synthesized by the reaction of the corresponding N-(4-oxocyclohexa-2,5-dien-1-ylidene)arylsulfonamides with N-chloramides. The biological activity of the synthesized compounds was studied on test cultures of Escherichia coli 67, Staphylococcus aureus 209-p, Mycobacterium luteum VKM B-868 and fungi Candida tenuis VKM Y-70, Aspergillus niger VKM F-1119 by the method of diffusion of substances into agar on a solid nutrient medium. The degree of activity of the test compounds was determined by the diameter of the zones of inhibition of growth of test cultures of microorganisms. The minimum inhibitory, bactericidal and fungicidal concentrations were determined by the method of serial dilutions of the substance in a liquid nutrient medium. At the studied concentration, the method of diffusion of substances into agar on a solid nutrient medium has shown that these compounds have low activity against bacteria Escherichia coli, Staphylococcus aureus, Mycobacterium luteum and fungi Candida tenuis, Aspergillus niger. The diameters of the zones of inhibition of growth of test cultures of microorganisms were less than 15 mm. In research by the method of serial dilutions of the substance in a liquid nutrient medium, they have been found to have bactericidal and fungicidal activity. The minimum inhibitory concentration of N-{2-hydroxy-5-[(4-methylbenzene-1-sulfonyl)amino]phenyl}benzamide was 31.2 μg/ml against bacteria Mycobacterium luteum. The minimum inhibitory concentration of N-{2-hydroxy-3-methyl-5-[(4-methylbenzene-1-sulfonyl)amino]phenyl}benzamide against fungi Aspergillus niger was 31.2 μg/ml. The minimum bactericidal concentration of N-{2-hydroxy-5-[(4-methylbenzene-1-sulfonyl)amino]phenyl}benzamide was 62.5 μg/ml against bacteria Mycobacterium luteum. Minimum fungicidal concentration of N-{3-[(4-methylbenzene-1-sulfonyl)imino]-6-oxocyclohexa-1,4-dien-1-yl}benzamide and N-{2-hydroxy-3-methyl-5-[(4-methylbenzene-1-sulfonyl)amino]phenyl}benzamide was 62.5 μg/ml in action to mold fungi Aspergillus niger.

Application of the Eluate Method of Phytotesting in Assessing the Waste Toxicity of the Process of Chemical Oxidation of Metals

The work describes the use of the eluate method of phytotesting in determining the toxic properties of waste from the metal chemical oxidation process. The experiment used two test cultures: radish (Raphanus sativus) and oat (Avena sativa L.) that showed the same toxicity results of studied samples. According to the established method, the research was carried out, mathematical models of the dependence of the phytoeffect on waste dilution were predicted, the safe waste dilution was calculated, and the results of the studies concluded on the classification of the risk of the waste under study.

ANTIMICROBIAL PROPERTIES OF ESSENTIAL OILS OF THE GENUS MONARDA PLANTS CULTIVATED IN BELARUS

The essential oils obtained by hydrodistillation method from the genus Monarda plants cultivated in Belarus were investigated. Using the technique of gas-liquid chromatography essential oil components were identified and determined. The dominant components of the essential oils were thymol (up to 27%), carvacrol (up to 29%), γ-terpinene (up to 22%) p-cimene (up to 35%). The distribution of dominant components of monarda essential oil depending on the plant chemotype and the method of preparing plant materials was shown. Antimicrobial activity of monarda essential oil against gram-positive and gram-negative bacteria test cultures was revealed. Gram-positive bacterial cultures were more sensitive to the inhibitory effect of monarda essential oils. Antimicrobial properties of dominant components (thymol, carvacrol, γ-terpinene and p-cimene) were investigated. Effect of dominant component concentration on the antimicrobial properties of monarda essential oils was established.

Search for antibacterial activity in a number of new S-derivatives (1,2,4-triazole-3(2H)-yl)methyl)thiopyrimidines

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.

INFLUENCE OF POLIGUANIDINE ON THE SELF-ORGANIZATION PROCESS IN CYSTEINE-SILVER SOLUTION

Выполнены реологические, структурные и антибактериальные исследования гидрогелей, получаемых на основе L-цистеина, ацетата серебра и полигексаметиленгуанидин гидрохлорида (ПГМГ-ГХ). Установлено, что водные растворы на основе L-цистеина и ацетата серебра хорошо смешиваются с водным раствором ПГМГ-ГХ, образуя прозрачные гидрогели. Предложена модель строения пространственной сетки геля. Показана высокая антимикробная активность гидрогеля по отношению к тест-культурам патогенных и условно-патогенных микроорганизмов. Rheological, structural, and antibacterial studies of hydrogels based on L-cysteine, silver acetate, and polyhexamethylene guanidine hydrochloride (PHMG-GC) have been carried out. It was found that aqueous solutions based on L-cysteine and silver acetate mix well with an aqueous solution of PHMG-GC, forming transparent hydrogels. A model of the structure of the spatial grid of the gel is proposed. High antimicrobial activity of the hydrogel was shown in relation to test cultures of pathogenic and opportunistic microorganisms.