Among all modern antibiotics, fluoroquinolones are well known for their broad spectrums of activity and efficiency toward microorganisms and viruses. However, antibiotic resistance is still a problem, which has encouraged medicinal chemists to modify the initial structures in order to combat resistant strains. Our current work is aimed at synthesizing novel hybrid derivatives of ciprofloxacin and norfloxacin and applying docking studies and biological activity evaluations in order to find active promising molecules. We succeeded in the development of a synthetic method towards 1,2,3-triazole-substituted ciprofloxacin and norfloxacin derivatives. The structure and purity of the obtained compounds were confirmed by ¹H NMR, ¹³C NMR, ¹⁹F NMR, LC/MS, UV-, IR- spectroscopy. Docking studies, together with in vitro research against Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Bacillus subtilis ATCC 6633, Pseudomonas aeruginosa ATCC 27853, Candida albicans NCTC 885-653 revealed compounds in which activity exceeded the initial molecules.

The aim of the work. Among all the representatives of four generations of fluoroquinolones ciprofloxacin (CIPRO) and norfloxacin (NOR) remain widely used and prescribed antibiotics in clinical practice. However, the problem of resistance towards them is gradually increasing. Thus, our investigation is dedicated to chemical modification of C-7 position of Ciprofloxacin and Norfloxacin ring as a promising solution to combat antibiotic resistance and open a pathway towards convenient synthesis of new fluoroquinolones derivatives. Materials and methods. The subjects of the research were N-piperazine-substituted ciprofloxacin and norfloxacin. The methods of molecular docking and organic synthesis were applied in the study. The structures of the obtained compounds were confirmed by 1H NMR, 13C NMR, 19F NMR, LC/MS, IR, UV spectroscopy. The antimicrobial activity was measured by the method of double serial dilutions against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Bacillus subtilis (ATCC 6633), Pseudomonas aeruginosa (ATCC 27853), Candida albicans (NCTC 885-653) and diffusion in agar method against clinical strains. The results. 7-(4-(2-Cyanoacetyl)piperazin-1-yl)-1-R-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acids were synthesized and their structures were confirmed. The obtained compounds showed the antibacterial activity on the reference level for double dilution method and exceeded control for “well” method. Conclusions. The current investigation revealed the promising route for the expanding of the existing fluoroquinolones diversity. Pharmacodynamics and pharmacokinetics changes could be achieved by chemical modifications of C-7 position of the initial ring. Further research utilizing the obtained compounds as starting ones opens a promising way to novel active molecules synthesis and combating the problem of antibiotic resistance

Provide updated data on the antimicrobial activity and chemical composition of original dry extracts from Lavandula angustifolia herb of Ukrainian origin. The aim – an experimental comparative study of the chemical profile and antimicrobial activity of the original dry extracts of Lavandula angustifolia herb and their effect on the ability to destroy biofilms of microbial cultures or prevent their formation in vitro. Materials and methods. The objects of the study are dry extracts obtained from the lavender herb with purified water and ethanol solutions (40 and 70 %). The main biologically active substances (BAS) of the extracts were determined by the Thin-layer chromatography and Absorption spectrophotometry methods. The microbiological properties of the test samples of the investigated plant extracts were studied in vitro by the two-fold serial dilutions method. The ability of microorganisms to form a biofilm was determined by the method of adhesion to polystyrene in flat-bottomed plastic plates. The optical density of the initial bacterial suspension was measured on the Densi-La-Meter device, and the density of inoculated bacterial cells on the Multiskan EX photometer at a wavelength of 540 nm. The study of the antimicrobial activity of water and ethanol extracts of lavender herb in a wide range of concentrations was carried out by the agar diffusion method in the "wells" modification, which is commonly used in microbiological practice. Results. Water and water-ethanol extracts of lavender of Ukrainian origin were obtained. Terpenoids (linalool, linylyl acetate and traces of 1,8-cineol), flavonoids (hyperoside, isoquercitrin), and hydroxycinnamic acids (rosmarinic, chlorogenic acids) were identified in the extracts. The total content of phenolic compounds is 2.02–2.60 mg/g, flavonoids – 1.46–3.17 mg/g. The largest amount of BAS was extracted with 70 % ethanol. According to the results of experimental studies, the extracts of the lavender herb, obtained by extraction with a water-ethanol solution (40 and 70 % ethanol) at a concentration of 1 mg/ml, have antimicrobial properties against a wide range of infectious agents (S. aureus, E. coli, K. pneumoniae, P. aeruginosa, C. albicans). Studies of the influence of test samples of lavender extracts at a concentration of 1 mg/ml on the ability of microorganisms (S. aureus, E. coli, K. pneumoniae, P. aeruginosa) to form biofilms demonstrated that the highest inhibitory activity against biofilm formation was found in the case of the action of test of a sample of phytoextract obtained by extraction with a water-ethanol solution (40 % ethanol), which accounted for S. aureus ‒ 57.8 %, P. aeruginosa – 66.7 %. A wide spectrum of antimicrobial action was established for the tested lavender phytoextracts under the conditions of application of the concentration range of 10-60 μg/ml. The best spectrum of antimicrobial action and the highest activity corresponds to the lavender extract, obtained by extraction with 70 % ethanol, with the effect depending on the concentration. Conclusion. The lavender herb of Ukrainian origin is a promising and affordable source of potential antimicrobial active pharmaceutical ingredients (API). Water-ethanol lavender extract (70 % ethanol), according to research results, has shown high antimicrobial and antifungal potential. According to preliminary data, antimicrobial activity correlates with the content of phenolic compounds. The obtained results may be useful for the search for original substances for the complex correction of symptoms of neurological deficits of infectious etiology

Scientific data on the pharmacodynamics of dry extracts of Bupleurum aureum and Salsola collina L. based on the results of studying the antimicrobial effect and the similar effect of co-trimoxazole when they are used together have been supplemented. The investigated phytoextracts do not show antimicrobial properties, but they do not change the antimicrobial effect of co-trimoxazole when they are used in combination. The aim of the study was to experimentally investigate the antimicrobial effect of extracts of Bupleurum aureum and Salsola collina L. and establish the possible antagonistic effect of these extracts on the antimicrobial drug co-trimoxazole when used together. Materials and methods. The research was conducted in May 2016. Screening of the antimicrobial effect of extracts of Bupleurum aureum and Salsola collina L. and establishing of the possible antagonistic effect of these extracts on the antimicrobial drug co-trimoxazole when they are used together was carried out in the laboratory of the Department of Microbiology of the National Pharmaceutical University, which has a certificate of attestation 045/14 dated 28.10.2014. For determination of antimicrobial activity, the agar diffusion method ("well" method), which is based on the ability of medicinal substances to penetrate the agar layer, was used. A set of reference strains of microorganisms was used: S. aureus ATCC 6538, E. coli ATCC 8739, P. aeruginosa ATCC 9027, B. subtilis ATCC 6633, C. albicans ATCC 10231. Petri dishes were filled with two layers of solid nutrient medium. The lower layer - 10 ml of melted "cold" AGV agar (medium No. 3), the upper layer - nutrient medium for the corresponding test strain. After cooling the lower layer of agar, three thin-walled steel cylinders (inner diameter - 6.0±0.1 mm, height - 10.0±0.1 mm) were placed on it at an equal distance from each other and from the edge of the cup. The top layer was poured around the cylinders - 13.5 ml of agar, melted and cooled to 45-48°С, mixed with the seed dose of the test microorganism (1.5 ml of microbial suspension, the concentration corresponding to the type of microorganism). After cooling the upper layer of agar, the cylinders were removed with sterile tweezers and 0.25-0.3 ml of the studied drug was added to the resulting wells. The results were recorded after 24 h by measuring the zone of growth inhibition, including the diameter of the wells. Measurements were made with an accuracy of 1 mm, while focusing on the complete absence of visible growth. The obtained data were analyzed using the methods of variational statistics. The significance level is p<0.05. The studied plant extracts of Bupleurum aureum (aqueous and alcoholic) and Salsola collina L. (aqueous and alcoholic) were used in doses of 0.005 mg/ml and 0.01 mg/ml, which corresponded to doses of 5 mg/kg and 10 mg/kg. Experimental data were also processed by parametric (Newman-Keuls) and non-parametric (Mann-Whitney) methods of variational statistics, using the Statistica 6.0 statistical software package; differences were considered statistically significant at p<0.05. Results. At the final stage, the determination of the antimicrobial effect of water and alcohol extracts of Bupleurum aureum and Salsola collina L. at doses of 1 mg/ml and 5 mg/ml was carried out, and the effect of BAS of these extracts on the antimicrobial effect of co-trimoxazole when used together was determined. In the course of the study, it has been established, that the addition of the above-mentioned extracts to the co-trimoxazole formulation does not affect its initial antimicrobial properties. Conclusion. Today, drug-induced liver injury remains one of the most important problems of hepatology and pediatrics, pharmacological science pays a lot of attention to the search for new effective and harmless drugs with a hepatoprotective effect, and the improvement of existing drugs is primarily aimed at increasing their specificity and reducing side effects related to the pharmacological properties of the drug. Currently, there is increasing interest in medicinal plants as a source of various biologically active substances (BAS), which provide a wide spectrum of pharmacological action of the agent, which allows to immediately affect various links of the pathogenesis of liver diseases. The analysis of scientific sources made it possible to establish that medicinal products of plant origin, thanks to BAS, possess polymodality of effects and reveal a versatile complex effect on the course of pathological processes in the body. Most drugs are characterized by good tolerability, absence of withdrawal syndrome and toxicity to parenchymal organs. Medicinal plants are used not only as monopreparations, but also in combination with synthetic drugs and as raw materials for obtaining BAS

The rapid increase in the prevalence of multiple drug resistance of pathogenic microorganisms poses a critical threat to public health worldwide, which significantly contributes to the increase in patient mortality and morbidity. Classical agents, used in the past for treatment, are losing their effectiveness, moreover, many of the newer available drugs have already become targets for bacterial resistance mechanisms. As a result, the treatment of infections becomes more complicated, and the total costs of treatment increase. Purpouse. In this work, we aimed to evaluate the role of plasmids in the development of antibiotic resistance and discuss various mechanisms of bacterial resistance to antibiotics, such as enzymatic inactivation of the antibiotic, reduction of the permeability of the outer cell membrane for the antibiotic, modification of the target mainly due to mutation, active efflux of the drug from the bacterial cell through with the help of enzymatic pumps. Materials and methods: the search for sources of information was carried out in the databases PubMed, Medline, Web of Science, Google Scholar, as well as electronic repositories of higher education institutions and scientific institutions of Ukraine. Materials related to the research technology of genetic variability and modification of bacteria and mechanisms of resistance of microorganisms to antibiotics were selected. Results. As a result of evolutionary development, bacteria have acquired two separate genetic systems - chromosomal DNA and extrachromosomal, self-replicating genetic elements called plasmids. It is bacterial plasmids that play a key role in the diffusion of specific resistance genes, in particular to antibiotics. Plasmids are non-essential parts of bacteria and are double-stranded, circular, or linear DNA molecules capable of autonomous replication, allowing bacteria to adapt to a hostile environment. Today, scientists are most interested in two properties of bacteria, caused by plasmids, - antibiotic resistance and bioremediation. The latter determines the survival and development of bacteria in various adverse conditions, including resistance to pollutants, the ability to decompose different chemical compounds, or adaptation to new ecological niches. Conclusions. Plasmids carry genes for xenobiotic degradation and heavy metal resistance, making them useful for bioremediation of toxic chemicals in an environmentally safe manner. However, properties, such as antibiotic resistance, result from the excessive and uncontrolled use of these drugs in medicine, veterinary medicine, agriculture, and other fields. Under such conditions, there is a natural selection of those strains of pathogenic bacteria that are carriers of R-plasmids