Antimicrobial activity of [1,2,4]triazolo[4,3-а]pyrazin-8(7h)-one derivatives

Today the problem of microbial resistance to antibacterial agents becomes the global one. Antimicrobial drugs that are in the pharmaceutical market do not satisfy the needs of modern treatment regimens, particularly Hospital-acquired infections. Therefore, the search for new and effective means of this pharmacological group is an important task of medical chemistry.  From the literature it is known that derivatives of [1,2,4]triazolo[4,3-a]pyrazine show a wide range of biological actions, including antimicrobial and fungicidal. This makes it relevant microbiological study of primary derivatives of [1,2,4]triazolo[4,3-a]pyrazine for identifying promising compounds of the series and then study it in biological experiment.Using the PASS C&T (Prediction Activity Spectra for Substances: Complex & Training) program and based on published data, we have generated virtual library of derivatives of [1,2,4]triazolo[4,3-a]pyrazine. As a result, we have received 35 new synthetic compounds of 7 series that were not previously described in the literature. Materials and methods. The research of antimicrobial and fungicidal activity of the synthesized compounds was carried out in the laboratory of antimicrobial agents GA "Mechnikov Institute of microbiology and immunology" under the leadership of  PhD, senior scientist V.V.Kazmirchuka. The activity of the synthesized compounds were studied by conventional method of the two-fold serial dilutions in liquid and solid nutrient medium. For primary screening we have used a set of clinical and reference strains of microorganism: Escherichia coli ATCC 25922 (F-50), Staphylococcus aureus ATCC 25923 (F-49), Bacillus anthracoides ATCC 1312, Pseudomonas aeruginosa ATCC 27853, Candida albicans ATCC 885-653. As the reference preparations were chosen Palin - modern antimicrobial agent of class of fluoroquinolones, Nevigramon - nalidixic acid derivative and Fluconazole - modern antifungal agent. Activity of substances determined by the minimum bacteriostatic (MBstK) and minimal bactericidal (MBcK) concentrations. All experiments were accompanied by appropriate controls. Results and Discussion. As a result of microbiological screening of  35 compounds we have allowed to identify a number of derivatives of [1,2,4]triazolo[4,3-a]pyrazine-8(7H)-one with antimicrobial and antifungal activity. The most pronounced effect showed compounds that contains in their structure aryl moiety with halogen atom, or N-arylatsetamide group in position 3 or 2 of the heterocycle. Principal condition for the demonstration of antifungal activity is presence of Sulfur atom in the triazole cycle. Conclusions. The substance of the series N7-aryl/benzyl-3-thioxo-[1,2,4]triazolo[4,3-а]pyrazin-8(7H)-ones showed the best antimicrobial and antifungal activity of all synthesized compounds. Compound 7-(3-chloro-2-methyl-phenyl)-3-thioxo-[1,2,4]triazolo[4,3-а]pyrazin-8(7Н)-one 4{4} showed high values of antimicrobial activity against gram-negative microorganisms (МBstК – 12.5-25.0 mkg/ml, МBcК – 25.0-50.0 mkg/ml) and was the most promising for further development

Implications of R-parity violating supersymmetry for atomic and hadronic EDMs

We calculate the electric dipole moments (EDM) of the neutral Hg(199) atom, deuteron, nucleons and neutral hyperons Lambda, Sigma(0) and Xi(0) in the framework of a generic SUSY model without R-parity conservation (RPV SUSY) on the basis of the SU(3) version of chiral perturbation theory (ChPT). We consider CP-violation in the hadronic sector induced by the chromoelectric quark dipole moments and CP-violating 4-quark effective interactions. From the null experimental results on the neutron and Hg(199) atom EDMs we derive limits on the imaginary parts of certain products Im(lambda' lambda'*) of the trilinear RPV-couplings and demonstrate that they are more stringent than those existing in the literature. Using these limits we give predictions for the EDMs of neutral hyperons. We also estimate the prospects of future storage ring experiments on the deuteron EDM and show that the expected improvement of the above limits in these experiments may reach several orders of magnitude.Comment: 11 pages, 1 figure, accepted for publication in Phys. Rev.

SOCIAL AND ETHNIC IDENTITIES MANIFESTATIONS DURING UKRAINIAN EMIGRANT’S ADAPTATION

In the article is presented a result of researching the manifestations of social and ethnic identities in the process of adaptation of Ukrainian emigrants who live abroad (28 countries in general).Emigrants have a high level of social identity, and also high levels membership satisfaction, thanks to being a member of their reference group; self-understanding and self-development, grade of belonging and the favor of informal relationships. Middle levels have the scales of in-group grade and cohesion. The low index has been revealed according to the intergroup relationships scale.Social identity levels of emigrants with different duration of living abroad are revealed only according to the intergroup competition.The results show the long emigrant adaptation to the new social environment until they reach the stage of activity, when, on the one hand, they feel like they are in their element, but on the other hand - they cannot forget that it is a different environment and the adaptation process has not been finished yet.In the article is presented a result of researching the manifestations of social and ethnic identities in the process of adaptation of Ukrainian emigrants who live abroad (28 countries in general).Emigrants have a high level of social identity, and also high levels membership satisfaction, thanks to being a member of their reference group; self-understanding and self-development, grade of belonging and the favor of informal relationships. Middle levels have the scales of in-group grade and cohesion. The low index has been revealed according to the intergroup relationships scale.Social identity levels of emigrants with different duration of living abroad are revealed only according to the intergroup competition.The results show the long emigrant adaptation to the new social environment until they reach the stage of activity, when, on the one hand, they feel like they are in their element, but on the other hand - they cannot forget that it is a different environment and the adaptation process has not been finished yet

Influence of tree-crown density on dominant plant species of the herb-shrub stratum in the zone of mixed forests

Forest ecosystems are among the most complex and dynamic biological systems of our planet. They play an important role in sustaining biodiversity, regulating the climate, and preserving water resources. Furthermore, they serve as natural filters, improving the quality of soil and air, and also preventing erosive processes. Forests create unique conditions for life of various species of plants and animals, which contributes to maintenance of the natural biodiversity and supports the stability of the ecosystem. Likewise, forests are important for the carbon cycle. They absorb a large amount of carbon, thus hindering global warming. Therefore, forest ecosystems are of paramount ecological value and their preservation is crucial for a balanced functioning of the planet. Our studies were carried out in the forest ecosystems of the Desna-Starohutskyi National Park, which is in the Ukrainian Polissia. The materials and methods of the study included systematic collection of the data on density of tree crowns, and also records of diversity of plants of the herb-shrub stratum in the chosen forest areas. Those data were analyzed using statistical methods. The study results revealed that the crown density has a significant effect on diversity of herb-shrub plants in the lower forest strata. Increase in crown density correlated with decrease in the light availability in the herb-shrub stratum. Change in the crown density towards increase significantly altered the conditions for competition between herbaceous and shrub species. Decrease in light availability led to shift in the competition ratio between the species, promoting dominance of more shade-loving species. Increase in crown density, which often reached 100%, made the competition more severe, especially for key resources (light, water, and nutrients). Because of this, species diversity in the herb-shrub stratum of the forest ecosystems was observed to decrease, and less adapted species were extruded. In general, change in tree-crown density in the forest ecosystem had a significant effect on the dynamics of herbaceous and shrub species, changing competitive relations and the structure of those plant communities. The results we obtained expand the knowledge about interactions between crown density and the structure of herb-shrub stratum, which gives perspectives for more efficient management of forest resources, and can also improve scientific identification and implementation of measures for protection of forest ecosystems

Розширення бази похідних 3,7-дизаміщених 7Н-[1,2,4]триазоло[4,3-а]піразин-8-онів як перспективних фармацевтичних агентів

A suitable and effective scheme for the synthesis of 3,7-disubstituted [1,2,4]triazolo[4,3-a]pyrazin-8(7H)-ones has been suggested and tested. It can provide a wide chemical diversity of the final products containing practically any substituent in position 3. The scheme previously developed starts from esters of oxalamic acid following with the cyclization of intermediate 3-hydrazinopyrazin-2-ones with carbonyl-containing compounds (ortho-esters or alkylcarbonic acid anhydrides). To introduce aryl or heteryl substituents in position 3 of the heterocyclic system we propose to use the reaction of 3-hydrazinopyrazin-2-ones with the corresponding carbonic acids preliminary activated by carbonyldiimidazole (CDI). The further cyclization is carried out by reflux for 24 hours in anhydrous DMFA. The structure of the compounds obtained has been proven by elemental analysis and 1H NMR spectroscopy data. Formation of [1,2,4]triazolo[4,3-a]pyrazin-8(7H)-one condensed system is in good correlation with spectral data, and is confirmed by the presence of signals of H-5 and H-6 protons of the pyrazinone fragment as doublets at d 7.15-7.28 ppm and d 7.50-7.59 ppm, respectively. The compounds synthesized are of particular interest as potential pharmacological objects with the cytotoxic, membrane-stabilizing, cerebroprotective, cardioprotective activity.Предложена и апробирована удобная и эффективная схема синтеза 3,7-дизамещенных 7Н-[1,2,4]триазоло[4,3-а]пиразин-8-онов, которая способна обеспечить большое химическое разнообразие конечных продуктов, содержащих практически любой заместитель в 3 положении. Предварительно разработанная нами схема исходит из эфиров оксаламовых кислот с последующей циклизацией промежуточных 3-гидразинопиразин-2-онов с карбонилсодержащими соединениями (ортоэфирами и ангидридами алкилкарбоновых кислот). Для введения в положение 3 гетероциклической системы арильных и гетерильных заместителей мы предлагаем использовать реакцию 3-гидразинопиразин-2-онов с со- ответствующими карбоновыми кислотами, которые предварительно активировали карбонилдиимидазолом (КДИ). Дальнейшую циклизацию осуществляли при кипячении в ДМФА в течение 24 часов. Структура полученных соединений доказана с помощью элементного анализа и данных 1Н ЯМР-спектроскопии. Образование конденсированной системы [1,2,4]триазоло[4,3-a]пиразин-8-она хорошо согласуется со спектральными данными и подтверждается присутствием сигналов протонов Н-5 та Н-6 пиразинонового фрагмента, которые проявляются как дублеты при d 7.15-7.28 м.д. и d 7.50-7.59 м.д. Синтезированные соединения представляют определенный интерес как потенциальные фармакологические объекты с цитотоксичной, мембраностабилизирующей, церебропротекторной, кардиопротекторной активностью.Запропоновано і апробовано зручну та ефективну схему синтезу 3,7-дизаміщених 7Н-[1,2,4]триазоло [4,3-а]піразин-8-онів, що здатна забезпечити велике хімічне різномаїття кінцевих продуктів, які можуть мати практично будь-який замісник у 3 положенні. Попередньо розроблена нами схема виходить з естерів оксаламових кислот з подальшою циклізацією проміжних 3-гідразинопіразин-2-онів з карбоніловмісними сполуками (ортоестерами і ангідридами алкілкарбонових кислот). Для введення в положення 3 гетероциклічної системи арильних та гетерильних замісників ми пропонуємо використовувати реакцію 3-гідразинопіразин-2-онів з відповідними карбоновими кислотами, які попередньо активували карбонілдіімідазолом (КДІ). Подальшу циклізацію здійснювали при кип’ятінні в ДМФА впродовж 24 годин. Структура отриманих сполук доведена за допомогою елементного аналізу та даних 1Н ЯМР- спектроскопії. Утворення конденсованої системи [1,2,4]триазоло[4,3-a]піразин-8-ону добре узгоджується зі спектральними даними та підтверджується наявністю сигналів протонів Н-5 та Н-6 піразинонового фрагменту, які проявляються як дублетні сигнали при d 7.15-7.28 м.ч. та d 7.50-7.59 м.ч., відповідно. Синтезовані сполуки представляють певний інтерес як потенційні фармакологічні об’єкти з цитотоксичною, мембраностабілізуючою, церебропротекторною, кардіопротекторною активностю

Особливості вживання антонімів у субмові медицини сучасної англійської мови

У статті досліджено й проаналізовано особливості антонімів у субмові медицини англійської мови. Визначено й проаналізовано антонімічні пари в медичній термінології різних галузей. (This article is devoted to peculiarities of antonyms in medical sublanguage of English. Antonymic pairs in medical terminology of different fields are determined and analyzed. Types of antonyms are studied and analyzed. Much attention is paid to antonyms of medical terminology.