For the first time, a pronounced biocidal activity of modified polymers with a porphyrin content of 21.4 mu M (0.002 wt%) against Staphylococcus aureus was demonstrated. In order to develop new biocidal polymer coatings, a study was carried out on diglycidyl ether of bisphenol A (DGEBA) and porphyrin-modified oligomeric diamine systems. The study investigated the solubility of porphyrins in oligomers through experimental and theoretical means, using Van Krevelen's approach of additive group contributions. Fully cured epoxy-amine polymer materials modified with varied free-base tetraarylporphyrins were obtained. The materials were studied by means of thermogravimetry, differential scanning calorimetry, UV-Vis and fluorescence spectroscopy. The proposed approach to the formation of modified epoxy-amine materials allows preservation of the photophysical properties of porphyrins, including their photostability. The addition of modifiers in 4.28-21.4 mu M range of concentrations makes it possible to keep the thermophysical and thermochemical properties of the polymer matrix.

The modification of epoxy-amine systems with reactive monomeric derivatives based on guanidine has been attempted in order to create novel polymer coatings suppressing activity of pathogens. Preliminary chemical interaction of these compounds with the epoxy component allows their covalent incorporation into the epoxy-amine network to ensure prolonged action of the coating. The synthesized guanidine hydrosalicylate, hydro-4-aminosalicylate, hydro-5-sulfosalicylate, and dihydro-5-sulfosalicylate have been characterized by means of elemental and thermal analysis. The degree of hydrochloride substitution with the organic salt residue and temperature of onset of the thermal decomposition under argon as well as temperatures of the salts vitrification and melting have been determined. Solubility of the synthesized salts in a diane-epoxy oligomer has been estimated. It has been shown that the substitution of hydrochloride with the organic residue noticeably decreases the temperature of the onset of the reaction with the epoxy oligomer. Average functionality of the guanidine salts in the reaction with the epoxy oligomer has been determined; it has been revealed that most of the N‒Н groups of the modifiers are involved in the reaction, in certain cases these being the residues of the organic salts. Stoichiometry of the guanidine‒epoxy oligomer binary mixtures as well as this of the adducts synthesized with the oligomeric amine curing agent Jeffamine D-230 are presented. The initial tests of the obtained films have revealed pronounced bacteriostatic activity towards the methicillin-resistant S. Еpidermidis at the guanidine hydrosalicylate content as low 1 wt

Для создания новых полимерных покрытий, подавляющих жизнедеятельность патогенных микроорганизмов, предпринята попытка модификации эпокси-аминных систем реакционноспособными производными мономерами на основе гуанидина. Предварительное химическое взаимодействие этих веществ с эпоксидным компонентом дает возможность ковалентно вводить их в эпокси-аминную сетку для обеспечения пролонгированного действия покрытия. Синтезированные гидросалицилат, гидро-4-аминосалицилат, гидро-5-сульфосалицилат и дигидро-5-сульфосалицилат гуанидина охарактеризованы методами элементного и термического анализа. Определены значения степени замещения гидрохлорида на остаток органической соли и температуры начала термодеструкции в аргоне, а также температуры стеклования и плавления солей. Оценена растворимость синтезированных солей в диановом эпоксидном олигомере. Показано, что замена гидрохлорида на органический остаток заметно снижает температуру начала реакции с эпоксидным олигомером. Установлена средняя функциональность солей гуанидина в реакции с эпоксидным олигомером, и обнаружено, что в химическое взаимодействие вступает большинство групп N‒Н модификаторов, в ряде случаев ‒ это остатки органических солей. Представлена стехиометрия бинарных систем гуанидин‒эпоксидный олигомер, а также стехиометрия синтезированных аддуктов с олигомерным аминным отвердителем Jeffamine D-230. Полученные пленки в первичных испытаниях продемонстрировали выраженную бактериостатическую активность по отношению к метициллин-резистентным S. еpidermidis уже при 1 мас. % гидросалицилата гуанидина, при этом значение показателя ингибирования пленкообразования составило 19.2%.

Natural compounds showing considerable inhibitory effect on formation of biofilms by P.aeruginosa were selected. Synergism of the compounds with gentamicin with respect to both the inhibition of the biofilm formation and the gentamicin antibacterial effect was stated.

The acquisition of resistance to the antibiotics and antibacterial agents used by microorganisms sets the task of finding new active disinfectants. It is known that compounds of the oligoguanidine class possess pronounced antibacterial properties, low toxicity, and can exhibit a prolonged biocidal effect, causing destruction of biofilms formed by pathogenic microflora. One of these compounds is branched oligohexamethylene guanidine hydrosuccinate (OHMG succ). The specified compound can be used as an active component in the development of a drug that acts on microbial dehydrogenases for the prevention and treatment of conjunctivitis of an infectious nature. In this regard, the purpose of this work is to study and visualize the mechanism of action of OHMG succ in relation to microbial dehydrogenases of Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa by colorimetric methods, to study its effect on the formation of biofilms and mature biofilms of E.coli, on its cell wall by scanning electron microscopy, as well as experimental evidence of the influence of OHMG succ on the morphology of several types of bacteria, yeasts, and molds that cause conjunctivitis, by atomic force microscopy. In addition, it was necessary to identify the dependence of cell segregation disturbance on the increasing concentration of OHMG succ. Thus, it was proved that OHMG succ affects not only the microbial dehydrogenases of certain Gram-negative bacteria, the mature biofilm of E.coli, but also its cell wall. The effect of OHMG succ on the morphology of several types of bacteria, yeast and mold fungi was also revealed. The indicated information shows that the creation of an antimicrobial drug based on OHMG succ is of interest, and this work may serve as the basis for the development of an innovative pharmacological drug for the treatment of conjunctivitis of an infectious nature.

Introduction. In order to standardize the quality indicators during the expected shelf life of the developed drug naltrexone hydrochloride in the form of a nasal spray containing a high concentration of poloxamer and benzalkonium chloride as a preservative, a microbiological study was carried out. The possibility of using the membrane filtration method for testing prototypes recommended by the State Pharmacopoeia XIV.Aim. Study and selection of test conditions for the «microbiological purity» indicator of nasal spray samples containing naltrexone hydrochloride.Materials and methods. As an object of research, a naltrexone hydrochloride nasal spray was used. When analyzing the microbiological purity, the membrane filtration method recommended in the State Pharmacopoeia XIV.Results and discussion. As part of the study, it was found that the samples of the drug meet the requirements for a microbiological indicator for drugs of category 2. Testing the suitability of the method for samples of the dosage form showed that the antimicrobial effect of the drug was completely removed by washing the filter, which was proved by inoculation of indicator test microorganisms, the quantitative and qualitative nature of growth, which did not differ from the control without the drug.Conclusion. As a result of the studies carried out, the optimal test conditions for the «Microbiological purity» indicator for the nasal spray containing naltrexone hydrochloride were selected and substantiated.

The effects of oligomycins on proliferation and apoptosis of lympholeucosis cells P388 of the wildtype strain and the strain resistant to vincristine were studied. It was shown that oligomycin B at a concentration of 0.3 ng/mL and oligomycin Sell, at 1 ng/mL inhibited cell proliferation. Oligomycins at high concentrations induced cell death by apoptosis type; the sensitivity to oligomycins of the wild-type cells and of the cells resistant to vincristine was the same. Oligomycin B was three times more effective than oligomycin ScII in reducing the cell survival: IC50 were 3 and 10 ng/mL, respectively. The same oligomycin sensitivity of the wildtype cells and of the strain resistant to vincristine can be accounted for by the inhibition of multidrug resistance of tumor cells with oligomycins, as was demonstrated by the oligomycin-induced increase in the rate of the formation of calcein from its actoxymethyl ester in the resistant strain cells.

Исследовали действие олигомицинов SCII и В на пролиферацию и апоптоз клеток лимфолейкоза Р388 и штамма, устойчивого к винкристину. Показано, что оба олигомицина в низких концентрациях: олигомицин В – до 0.3, олигомицин SCII – до 1 нг/мл подавляют пролиферацию клеток. В больших концентрациях олигомицины вызывают гибель клеток по типу апоптоза, причем чувствительность к олигомицинам клеток дикого типа и штамма, устойчивого к винкристину, одинакова. Олигомицин В в 3 раза более эффективно снижал выживаемости клеток, чем олигомицин SCII: IC50 составляет 3 и 10 нг/мл соответственно. Одинаковая чувствительность к олигомицинам клеток дикого типа и штамма, устойчивого к винкристину, объясняется тем, что олигомицины ингибируют множественную лекарственную устойчивость опухолевых клеток, что показано по увеличению скорости образования кальцеина из ацетооксиметилового эфира кальцеина в клетках устойчивого штамма.

Сравнили влияние олигомицинов SсII, F, В и циклоспорина А на множественную лекарственную устойчивость (МЛУ) клеток лимфолейкоза Р388BР и клеток рака гортани HEр-2. Установлено, что олигомицин SсII снижает откачку родамина 123 и кальцеина АМ из клеток НЕр-2 эффективнее, чем циклоспорин А, а в клетках Р388ВР циклоспорин А был эффективнее олигомицинов. Различия в эффективности циклоспорина А и олигомицинов в клетках разного типа, по-видимому, обусловлена экспрессией в них разных транспортных белков: Pgp в Р388ВР и других белков (например, одного из семи белков семейства MRP) в НEр-2.

The influence of oligomycins SCII, F and B on multidrug resistance of lympholeukosis cells P388VR and human larynx cancer cells HEp-2 was studied and compared with effects of cyclosporin A. It was shown that oligomycin SCII is more effective than cyclosporin A in reducing the pumping of rhodamine 123 and calcein AM from cells HEp2. For the P388VR cells cyclosporin A is more effective than oligomycins. Thus, oligomycin SCII is, apparently, a specific inhibitor of one of the transport proteins responsible for the multidrug resistance.

Eye infection is one of the temporary invalidity causes that can lead to blindness. The former antibacterial components of eye drops were polyhexamethylene guanidine hydrochloride and polyhexamethylene guanidine phosphate. Polyhexamethylene guanidine in the form of form of succinate with preserved activity and lover toxicity is described. The antibacterial activity spectra of polyhexamethylene guanidine succinate and polyhexamethylene guanidine hydrochloride were comparatively estimated.

Under the screening programme for antibiotics with antifungal and immunosuppressive activities, Streptomyces virginiae 17 producing an oligomycin complex was isolated. Separation of the complex by HPLC showed that it contained two components at a ratio of 8:2. The physico-chemical characteristics of the components were investigated. The structure of oligomycin was assessed by 13C NMR and 1H NMR.

Under the screening programme for organisms producing substances with hypolipidemic and antifungal activity Streptomyces sp. 17 was isolated. The taxonomic properties of the strain were investigated. Active compounds, i.e. oligomycin A and oligomycin SC-II were isolated from a complex biosynthetic product. Oligomycin A showed high antifungal activity whereas oligomycin SC-II had also moderate antibacterial activity.

Natural complex compounds with hipolipidemic activity, having considerable inhibitory effect on expression of bacteria virulence factors were isolated. Inhibitory properties of the compounds with respect to pyocyanine and protease formation, as well as their influence on the quorum sensing mechanism in Chromobacterium violacium were shown.

Comparative antimicrobial activity of lactoferrins from various sources (native lactoferrin from Laprot, human hololactoferrin, recombinant human lactoferrin isolated from the cultural medium of permissive cell culture transfected using pseudoadenovirus nanostructure with the human lactoferrin gene, and native bovine lactoferrin) was studied to prove the possibility of their use for development of antimicrobial drugs. It was shown that all the substances were active against the Bacillus standard strains. The antibacterial activity was almost independent of the degree of saturation the lactoferrin molecules with Fe3+. The native human lactoferrin was more active than hololactoferrin against Candida when evaluated by the minimum inhibitory concentration (MIC). Fe(3+)-Non aturated recombinant human lactoferrin demonstrated the antimicrobial activity (by MIC) similar to that of the native human lactoferrin. The results showed that native and recombinant human lactoferrins might be used for the development of intravenous and intracavitary dosage forms, while the native bovine lactoferrin could be useful in development of oral drugs.

Natural compounds showing considerable inhibitory effect on formation of biofilms by P. aeruginosa were selected. Synergism of the compounds with gentamicin with respect to both the inhibition of the biofilm formation and the gentamicin antibacterial effect was stated.

Complex compounds produced by fungal cultures of Lecanicilium and Beauveria with both high hypolipidemic and antioxydant activities were screened. Two fractions of the hypolipipidemic compounds with antioxidant activity of 95 and 75% in a dose of 25 mcg/ml were isolated.

In the programme for screening sterol synthesis inhibitors with the use of actinomycetes and fungi 702 strains were tested. The effect of alcohol extracts of the mycelium of fungi and actinomycetes at a dilution of 1/10(3) on sterol synthesis by the Hep G2 hepatome cells was determined by incorporation of 3H acetate into sterols and proteins. Lovastatin (200 pg/ml) was used as the control: the sterol synthesis was decreased by 49 +/- 4% without inhibiting the protein synthesis. A number of the cultures produced compounds inhibiting under the experimental conditions the synthesis of sterols by 70 to 80% with simultaneous inhibition of the protein synthesis at least by 60 to 70%. Three compounds from that group produced by streptomycetes were subjected to a more detailed investigation. The compounds were demonstrated to be active antifungal antibiotics (MIC 0.1-1 mcg/ml). In a dose of 0.1-1 mcg/ml they showed high immunosuppressive activity in models of lymphocyte transformation in mice, whereas cyclosporin was active in a dose of 1 mcg/ml. Therefore, the model for screening hypolipidemic compounds could be considered useful for screening promising natural immunosuppressors.