Синтез, дослідження 6-((5-фенетил-4-R-1,2,4-триазол-3-ілтіо)піридин-3-іл)-(алкіл, гетерил)метанімінів та їх похідних

In the pharmaceutical practice directly related to the search of biological active substances and their introduction into medicine or veterinary it is generally recognized that a successful choice of the research object is a prerequisite for a positive final outcome to create original effective and low-toxic drugs. At present, derivatives of 1,2,4-triazoles containing pyridine deserve special attention. That is why the synthesis and study of physicochemical properties of new compounds, which contain 1,2,4-triazole and pyridine rings, are important tasks of modern synthetic and pharmaceutical chemistry.Aim. To study the reactions associated with formation and transformation of 6-((5-phenethyl-4-R-1,2,4-triazole-3-ylthio)pyridine-3-yl)-(alkyl-, heteryl)methanimines and their recovery, study physicochemical properties of new compounds synthesized. Materials and methods. 6-((5-phenethyl-4-R-1,2,4-triazole-3-ylthio)pyridine-3-yl)-(alkyl-, heter-yl)methanimines were obtained by the mixture from 6-(5-phenethyl-4-R-1,2,4-triazole-3-ylthio)pyridine-3-amine and aldehydes. The synthesis was carried out in the acetic acid medium. The mixture was kept at room temperature for 6 h. 6-((5-phenethyl-4-R-1,2,4-triazole-3-ylthio)pyridine-3-yl)-(alkyl-, heteryl)methanimines were reduced in the 1,4-dioxane medium. As a reducing agent sodium borohydride was used. Results and discussion. As a result of synthetic transformations 17 new compounds have been obtained, the structure of the compounds synthesized has been confirmed by modern complex of physicochemical methods of analysis (IR-spectrophotometry, elemental analysis), and their individuality has been proven on an Agilent 1260 Infinity HPLC high-performance liquid chromatograph equipped with an Agilent 6120 mass spectrometer.Conclusions. The preparative method for the synthesis of 6-((5-phenethyl-4-R-1,2,4-triazole-3-ylthio)pyridine-3-yl)-(alkyl-, heteryl)methanimines and 6-(5-phenethyl-4-R-1,2,4-triazole-3-ylthio)-N-(alkyl-, heteryl)pyridine-3-amines has been developed.В фармацевтической практике, непосредственно связанной с поиском биологически активных веществ и их введением в медицину или ветеринарию, общепринято, что успешный выбор объекта исследования является предпосылкой для положительного конечного результата, для создания оригинальных эффективных и малотоксичных лекарств. На данный момент особого внимания заслуживают производные 1,2,4-триазолов, которые содержат пиридин. Именно поэтому синтез и изучение физико-химических свойств новых соединений, содержащих 1,2,4-триазольное и пиридиновое кольца, являются важной задачей современной синтетической и фармацевтической химии.Цель. Изучить реакцию образования 6-((5-фенетил-4-R-1,2,4-триазол-3-илтио)пиридин-3-ил)-(алкил, гетерил)метаниминов и их селективного восстановления, исследовать физические и химические свойства новых синтезированных соединений.Материалы и методы. Для получения 6-((5-фенетил-4-R-1,2,4-триазол-3-илтио)пиридин-3-ил)-(алкил-, гетерил)метаниминов использовали 6-(5-фенетил-4-R-1,2,4-триазол-3-илтио)пиридин-3-амины и альдегиды. Синтез проводился в среде кислоты уксусной. Смесь оставляли при комнатной температуре на 6 часов. 6-((5-Фенетил-4-R-1,2,4-триазол-3-илтио)пиридин-3-ил)-(алкил-, гетерил)метанимины были восстановлены в среде 1,4-диоксана. В качестве восстановителя был использован натрия боргидрид.Результаты и их обсуждение. В результате синтетических превращений получено 17 новых соединений, структуру синтезированных соединений подтверждено благодаря современному комплексу физико-химических методов анализа (ИК-спектрофотометрии, элементного анализа), а их индивидуальность подтверждена исследованием на высокопроизводительном жидком хроматографе Agilent 1260 Infinity HPLC, оборудованном масс-спектрометром Agilent 6120.Выводы. Разработан препаративный метод синтеза 6-((5-фенетил-4-R-1,2,4-триазол-3-илтио)пиридин-3-ил)-(алкил-, гетерил)метаниминов и 6-(5-фенетил-4-R-1,2,4-триазол-3-илтио)-N- (алкил-, гетерил)пиридин-3-аминов.У фармацевтичній практиці, яка безпосередньо пов’язана з пошуком біологічно активних речовин та їх введенням у медицину або ветеринарію, загальним є те, що успішний вибір об’єкта дослідження є необхідною умовою для позитивного кінцевого результату та для створення оригінальних ефективних та малотоксичних препаратів. На цьому етапі на особливу увагу заслуговують похідні 1,2,4-триазолів, що містять піридин. Саме тому синтез та вивчення фізико-хімічних властивостей нових сполук, що містять 1,2,4-триазольний та піридиновий фрагмент, є важливими завданнями сучасної синтетичної та фармацевтичної хімії.Мета. Вивчити реакцію утворення 6-((5-фенетил-4-R-1,2,4-триазол-3-ілтіо)піридин-3-іл)-(алкіл, гетерил)метанімінів та їх селективного відновлення, дослідити фізичні та хімічні властивості нових синтезованих сполук.Матеріали та методи. Для отримання 6-((5-фенетил-4-R-1,2,4-триазол-3-ілтіо)піридин-3-іл)-(алкіл-, гетерил)метанімінів використано 6-(5-фенетил-4R-1,2,4-триазол-3-ілтіо)піридин-3-аміни та альдегіди. Синтез проводився в середовищі кислоти оцтової. Суміш залишали при кімнатній температурі на 6 годин. 6-((5-Фенетил-4-R-1,2,4-триазол-3-ілтіо)піридин-3-іл)-(алкіл-, гетерил)метаніміни були відновлені в середовищі 1,4-діоксану. В якості відновника використано натрію боргідрид.Результати та їх обговорення. В результаті синтетичних перетворень отримано 17 нових сполук, структуру синтезованих сполук підтверджено завдяки сучасному комплексу фізико-хімічних методів аналізу (ІЧ-спектрофотометрії, елементного аналізу), а їх індивідуальність підтверджена дослідженням на високопродуктивному рідинному хроматографі Agilent 1260 Infinity HPLC, обладнаному мас-спектрометром Agilent 6120.Висновки. Розроблено препаративний метод синтезу 6-((5-фенетил-4-R-1,2,4-триазол-3-ілтіо)піридин-3-іл)-(алкіл-, гетерил)метанімінів і 6-(5-фенетил-4-R-1,2,4-триазол-3-ілтіо)-N-(алкіл-, гетерил)піридин-3-амінів

КОМП’ЮТЕРНЕ ПРОГНОЗУВАННЯ ГОСТРОЇ ТОКСИЧНОСТІ ПОХІДНИХ 5-ФЕНЕТИЛ-4-R-3-ТІО(АМІНО)-1,2,4-ТРІАЗОЛУ ЗАВДЯКИ GUSAR-ONLINE ПРОГНОЗУ

An important step in the development of a new drug is the prediction of its toxicity by computer screening using the program GUSAR-online. The purpose of this work is an online prediction of acute toxicity among new derivatives of 5-phenethyl-4-R-3-thio(amino) 1,2,4-triazoles. Computer prediction of acute toxicity of 5-phenethyl-4-R-3-thio(amino)- 1,2,4-triazole derivatives was performed according to the structural formulas of the compounds in the online version of the GUSAR-online program.GUSAR-online prediction for 5-phenethyl-4-R-3-thio(amino)-1,2,4- triazole derivatives was performed during the research. It was found that the average lethal dose of LD50 is from 56.1 to 2396.0 mg / kg. Based on this, all compounds are low-toxic and virtually non-toxic substances.An important step in the development of a new drug is the prediction of its toxicity by computer screening using the program GUSAR-online. The purpose of this work is an online prediction of acute toxicity among new derivatives of 5-phenethyl-4-R-3-thio(amino) 1,2,4-triazoles. Computer prediction of acute toxicity of 5-phenethyl-4-R-3-thio(amino)- 1,2,4-triazole derivatives was performed according to the structural formulas of the compounds in the online version of the GUSAR-online program.GUSAR-online prediction for 5-phenethyl-4-R-3-thio(amino)-1,2,4- triazole derivatives was performed during the research. It was found that the average lethal dose of LD50 is from 56.1 to 2396.0 mg / kg. Based on this, all compounds are low-toxic and virtually non-toxic substances

The role of students’ individual work in the formation of professional competences of future doctors.

Modern requirements for training of high-skilled specialists require the implementation of international medical and educational standards in the educational and integrative process. Formation of cognitive activity, pursuance of professional development, the necessity to correspond to world standards medical students’ of gained knowledge. Medical students’ individual work is very important for medical students’ education because it helps to systematize and use knowledge that was gained in practical classes. The aim of the work – to analyze the forms of students’ individual work, used at in the Department of Internal Medicine 2 and Phthisiology, in order to improve the educational process and to form the future doctor’s medical judgment, their ability to self-improvement and self-education. The recommended hours attempted for students’ individual work is 90 out of the total of 240 hours assigned to the discipline in teaching the module “internal diseases” for the 5th year students at the Depertment of Internal Medicine 2 and Phthisiology. In studying the discipline of "internal diseases" in the 5th year one of the main tasks of medical student’s occupation training is mastering ability of assimilation on his own, of knowledge and refresh it, and then to use knowledge effectively in the future career. The difference of the individual work lies in the fact that students can study individually choosing the necessary kind of extracurricular activity according to their interests. In addition, the lack of strict grading by the teacher has more advantages compared to practical classes. The curriculum, the teacher’s tasks and methodological materials determine the content of the individual work. The article presents the three main directions of students’ individual work in teaching discipline of "internal diseases" for students of the 5th year as: students’ individual work in classroom learning, students’ individual work individual work under the teacher’s supervision. When discussing the results of individual work, students learn to think critically, communicate with each other, and make their own well-thought-out (educated) decision. Well-structured process of the individual work encourages medical students to its qualitative fulfillment and it is a significant motivation for further professional growth. Significant reserves to increase its efficiency inherent in the use of modern computer technology. Medical students’ individual work should be considered as one of the necessary stages of a modern doctor training. The latest information technologies and individual scientific projects adoption into the educational process leads to efficiency improvement and it forms new future doctor’s professional competences

КРОС-ПЛАТФОРМНЕ ОБ’ЄДНАННЯ ДАНИХ МІКРОМАСИВ-ЕКСПЕРИМЕНТІВ ТА ЙОГО ВПЛИВ НА ЗНАЧЕННЯ ГЕННОЇ ЕКСПРЕСІЇ ПРИ АНАЛІЗІ ЗРАЗКІВ РАКОВИХ ПУХЛИН МОЛОЧНОЇ ЗАЛОЗИ ЛЮДИНИ

Introduction. Currently advances in different fields of biology and medicine accumulated large amount of high-throughput microarray datasets. It allows comparing, merging and analyzing such data in order to get more informative and statistically significant results. However, the process of cross-platform microarray data integration is complicated by different platform designs, that is the kind of probes used, the hybridization paradigm, the labeling and production methods. Such characteristics of microarray platforms should be considered when analyzing datasets from one study and even more when merging datasets.В различных областях биологии и медицины накопилось значительное количество данных широкомасштабных исследований генной экспрессии с использованием микромасив-технологий. Поэтому возникает насущная необходимость в сравнении, объединении и анализе этих данных с целью повышения информативности и статистической достоверности результатов анализа.У різних галузях біології та медицини накопичилася значна кількість даних широкомасштабних досліджень генної експресії за використання мікромасив-технологій. Тому виникає нагальна потреба в порівнянні, об'єднанні й аналізі цих даних з метою підвищення інформативності та статистичної достовірності результатів аналізу. Однак, процес об'єднання результатів мікромасив-експериментів на базі крос-платформного аналізу ускладнений існуванням багатьох мікроарей-платформ, різних за технологією виготовлення, методикою нанесення проб на чип і різновидністю дизайну проб. Ці особливості кожного з досліджень повинні бути враховані при обробленні та аналізі результатів мікромасив-експериментів, отриманих як на однакових, так і на різних платформах

О МНОГООБРАЗИИ 3N АЛГЕБР ЛЕЙБНИЦА И ЕГО ПОДМНОГООБРАЗИЯХ

Article represents the review of properties of variety left nilpotent of the class not more than 3 Leibniz algebras and its subvarieties. The characteristic of basic field will be equal to zero. A Leibniz algebra is an algebra with multiplication satisfying the Leibniz identity (xy)z = (xz)y + x(yz). In other words, the operator of right multiplication is a derivation of the algebra. Since Leibniz identity equivalent to the Jacobi identity, in case multiplication in Leibniz algebra is anti-commutative, it is obvious that the Leibniz algebras are generalizations of concept of Lie algebtras. The variety 3N is defined by identity x(y(zt)) ≡ 0 possesses some extreme properties (properties, which any its own subvariety possesses, while the variety doesn’t possess them). As the basic field has zero characteristic zero, then any identity is equivalent to the system of multilinear identities, that allows to use well-developed theory of representations of the symmetric group. In addition to using the classical results of the structural theory of rings and linear algebras, representation theory, as well as the structural theory of varieties of associative algebras, and the use of original asymptotic and combinatorial arguments with application identities and Young diagrams allowed to receive the following results: the variety 3N has almost exponential growth, almost polynomial growth of colength, almost finite multiplicity. Moreover, this variety has almost associative type, that is his own cocharacter any subvarieties lies in the hook. In this work are considered also subvarieties of variety 3N: held description of the complete list of varieties with almost polynomial growth; proved integrality of exponents any proper subvariety of variety 3N. Статья представляет собой обзор свойств многообразия левонильпотентных ступени не выше трех алгебр Лейбница и его подмногообразий. Характеристика основного поля на протяжении всей работы предполагается равной нулю. Алгеброй Лейбница над некоторым полем называется линейная алгебра над этим полем, удовлетворяющая так называемому тождеству Лейбница (xy)z ≡ (xz)y + x(yz), которое превращает правое умножение на элемент алгебры в дифференцирование этой алгебры. Поскольку тождество Лейбница по модулю антикоммутативности эквива- лентно тождеству Якоби, то, очевидно, что алгебры Лейбница являются обобщением понятия алгебр Ли. Многообразие 3N определяется тождеством x(y(zt)) ≡ 0 и обладает рядом экстремальных свойств (свойства, которыми обладает любое его собственное подмногообразие, в то время как само многообразие ими не обладает). В силу нулевой характеристики основного поля любое тождественное соотношение эквивалентно системе полилинейных тождеств, что позволяет, использовать хорошо развитую теорию представлений симметрической группы. Кроме использования классических результатов структурной теории колец и линейных алгебр, теории представлений, а также структурной теории многообразий ассоциативных алгебр, использование оригинальных комбинаторных и асимптотических рассуждений с применением тождеств, диаграмм Юнга позволили получить следующие результаты: многообразие 3N имеет почти экспоненциальный рост, почти полиномиальный рост кодлины, почти конечные кратности. Кроме того, данное многообразие является многообразием почти ассоциативного типа, то есть кохарактер любого его собственного подмногообразия лежит в крюке. В данной работе рассматриваются также свойства подмногообразий многообразия 3N: проводится описание полного списка подмногообразий почти полиномиального роста; доказывается целочисленность экспоненты любого собственного подмногообразия многообразия 3N.

Organizational and economic transformations towards the greening of agro-industrial production

The increase in the production of agricultural products and food supplies in excess of regulatory needs and the provision of food safety in Russia led to the expansion of the export of agricultural products and the change in the course of the development of the agro-industrial complex from import substitution to export-oriented production. However, the entry to world food markets requires high quality of products from manufacturers and its certification in accordance with world standards. The article presents the organizational and economic transformations towards the greening of agro-industrial production, namely, the use of the resource potential, the involvement of Russian manufacturers in the production of environmentally friendly products and the development of organic agriculture; the mechanisms for solving the set problems are substantiated.peer-reviewe

Microorganisms for bioremediation of soils contaminated with heavy metals

Heavy-metal contaminants are one of the most relevant problems of contemporary agriculture. High toxicity and the ability to accumulate in soils and crops pose a serious threat to food security. To solve this problem, it is necessary to accelerate the pace of restoration of disturbed agricultural lands. Bioremediation is an effective treatment for agricultural soil pollution. It relies on the ability of microorganisms to remove pollutants. The purpose of this study is to create a consortium based on microorganisms isolated from technogenic sites for further development in the field of soil restoration in agriculture. In the study, promising strains that can remove heavy metals from experimental media were selected: Pantoea sp., Achromobacter denitrificans, Klebsiella oxytoca, Rhizobium radiobacter, and Pseudomonas fluorescens. On their basis, consortiums were compiled, which were investigated for the ability to remove heavy metals from nutrient media, as well as to produce phytohormones. The most effective was Consortium D, which included Achromobacter denitrificans, Klebsiella oxytoca, and Rhizobium radiobacter in a ratio of 1:1:2, respectively. The ability of this consortium to produce indole-3-acetic acid and indole-3-butyric acid was 18.03 μg/L and 2.02 μg/L, respectively; the absorption capacity for heavy metals from the experimental media was Cd (56.39 mg/L), Hg (58.03 mg/L), As (61.17 mg/L), Pb (91.13 mg/L), and Ni (98.22 mg/L). Consortium D has also been found to be effective in conditions of mixed heavy-metal contamination. Due to the fact that the further use of the consortium will be focused on the soil of agricultural land cleanup, its ability to intensify the process of phytoremediation has been studied. The combined use of Trifolium pratense L. and the developed consortium ensured the removal of about 32% Pb, 15% As, 13% Hg, 31% Ni, and 25% Cd from the soil. Further research will be aimed at developing a biological product to improve the efficiency of remediation of lands withdrawn from agricultural use

Proton-induced activation cross sections in the energy range below 1 GeV

(Abridged) Modern studies and industrial applications related to the design, radiation protection, and reliability of nuclear facilities, medical applications, as well as space research and exploration are relying on extensive simulations and modeling. Computer codes realizing semi-classical and quantum molecular dynamics (QMD) approaches are often employed to make up for the lack of accelerator data on many nuclear reactions at intermediate and high energies (>10s of MeV/n) and are in high demand. This contribution focuses on the methodology of generating reliable proton-induced cross sections in the energy range below 1 GeV. We developed a problem-oriented computer framework based on MCNPX and CASCADE/INPE codes to calculate activation cross section data at intermediate and high energies. Goodness of the fits of nucleon-nucleus interaction models to the existing data is evaluated based on elaborated algorithms. The method is based on the analysis of a large set of data and calculated cross sections for different targets and residual nuclei in a wide range of proton energies using numerous criteria. In practice, this could be done by tuning the model parameters and algorithms to fit required experimental data subset, or through achieving unification and consistency of fundamental parameters for all considered reactions. The presented framework is pursuing the latter approach. We use proton-induced reactions on Si and Fe nuclei to illustrate the application of the developed multi-criteria algorithm, where we use all data below 1 GeV available from the EXFOR data library and the IAEA CRP "Benchmark of Spallation Models." We show that the analysis of the predictive power of various intermediate and high-energy models based on the multi-criteria algorithm allows more sophisticated selection of appropriate models in a given energy range and residual nuclei domain.Comment: A poster E1.16-0085-21 presented at an event E1.16 "Origin of Cosmic Rays," 43th COSPAR Scientific Assembly (hybrid), 28 Jan - 4 Feb 2021, Sydney, Australia. For a full agenda of the event E1.16, see https://www.cospar-assembly.org/admin/session_cospar.php?session=90

Challenges Associated with Forming Generic Names for Herbal Medicinal Products

INTRODUCTION. The lack of a unified approach to establishing generic (grouping) names, which must be specified for herbal medicinal products, presents a challenge to developers and manufacturers preparing registration dossiers, as well as to regulators reviewing their submissions.AIM. This study aimed to set forth common approaches to establishing generic names for herbal medicinal products based on studying the terminology used in different legal systems.DISCUSSION. The authors analysed the pharmaceutical terminology used for herbal medicinal products at national and  supranational  levels  in  the  Russian  Federation, the Eurasian Economic Union (EAEU), the Republic of Belarus, the European Union (EU), the United Kingdom, and the United States. This analysis revealed differences in the terminology used in the Russian Federation and the EAEU. For example, the definition of “herbal drugs” is more detailed in the EAEU documents than in the Russian documents, and the definitions of “herbal drug preparation” and “herbal medicinal product” are not the same as well. The authors analysed the approaches to generic naming of herbal medicinal products and detected some improperly formed generic names in the regulatory documentation and Russian State Register of Medicinal Products. In addition, the study revealed variability in generic names proposed by different manufacturers for medicinal products having the same trade name. The authors described the selection of generic names for herbal medicinal products, including fatty or essential oils and liquid or dry extracts. The authors touched upon generic naming of some types of source plants when the morphological group of the herbal drug or the name of the source plant is ambiguous, the Latin name and the Russian name of the herbal drug are inconsistent, or the Latin name of the resulting product or the morphological group of the herbal drug is erroneous. The authors systematised and unified approaches to generic naming of herbal medicinal products with due regard to the species of source plants, the morphological groups of herbal drugs, and the production technology and composition of herbal medicinal products. The authors analysed typical errors in establishing conventional and generic names for herbal drugs and herbal medicinal products associated with incorrectly identified morphological groups of herbal drugs, incorrect source plant names, mismatching structures of Latin and Russian names of herbal drugs, erroneous Latin names of the resulting products, or wrongly assigned morphological groups of herbal drugs.CONCLUSIONS. According to the analysis of  the  names  of  herbal  drugs,  herbal drug preparations, and herbal medicinal products used in  the  State  Pharmacopoeia of the Russian Federation (editions XI–XV), the Pharmacopoeia of the EAEU, and the European Pharmacopoeia, the terminology of these legal systems is harmonised to a high degree. The alignment of terminology is the closest between the regulatory documents of  the  EAEU  and the EU. The terms and names used in Russia need further unification. The results of this study can be used in Russian pharmacopoeial practice to develop regulatory documents, prepare  registration dossiers, and conduct expert reviews of submissions for herbal medicinal products