The aim of our work is to synthesize new S-derivatives in the series of ((1,2,4-triazol-3(2H)-yl)methyl)thiopyrimidines and to study their antioxidant activity, to identify the most promising compound using molecular docking and kinetic parameters. Materials and methods. The 1H and 13C NMR spectra were recorded on a Bruker AC-500 spectrometer. LC-MS was recorded on an Agilent 1260 Infinity HPLC system equipped with a diode-array detector and proton ionization. Elemental analysis (C, H, N, S) was performed on an ELEMENTAR vario EL cube. Molecular docking was performed using the AutoDock 4.2.6 program. Free radical absorption was measured using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical assay. Results. A series of S-acyl derivatives of 4-methyl-5-((pyrimidin-2-ylthio)methyl)-4H-1,2,4-triazole-3-thiols were synthesized through alkylation and subsequent cyclization. The structure of the obtained compounds was confirmed by ¹H and ¹³C NMR spectroscopy. Antiradical activity was evaluated using the DPPH test, with compound (6) exhibiting the highest activity, surpassing ascorbic acid. Molecular docking with cytochrome c peroxidase (PDB: 2X08) confirmed strong binding interactions, highlighting the potential of these derivatives as antioxidants. Conclusions. Three compounds (1, 6, 8) exhibited higher activity than the reference drug, the natural antioxidant ascorbic acid. This high activity may be associated with the presence of pharmacophore fragments, particularly the pyrimidine skeleton and the sulfur atom linked to the 1,2,4-triazole. The IC50 for the most active compound was calculated as 4.458±1 µM, which is 27 times more effective than ascorbic acid. Molecular docking results showed that compounds 4 and 6 had the lowest binding energies, making them the most effective compounds in terms of antioxidant activity

In the literature, there is insufficient information on the synthesis of compounds in a series of pyrimidine-2-thiol derivatives containing a five-membered nitrogen-containing heterocyclic fragment; at the same time, there are a sufficient number of examples, demonstrating the synthetic and biological potential for compounds of this kind. The relevance of the study “structure – acute toxicity” relationship in a number of newly synthesized derivatives of 1,2,4-triazole-3(2H)-thione with pyrimidine-2-thiol is due to the synthesis of potential low molecular weight interferon inducers and antitumor agents, the search for molecular descriptors of their structure, important for establishing “structure – acute toxicity” laws, as a system for evaluating the biological effects of compounds. Therefore, it is strategically and economically justified to conduct a study of the acute toxicity of synthesized compounds as a priority. The aim of the work is targeted synthesis of a number of S-derivatives (1,2,4-triazole-3(2H)-yl)methyl)thiopyrimidines and the establishment of the “structure – acute toxicity” relationship. Materials and methods. A modern set of physical-chemical research methods was used to study the compounds. The study of the acute toxicity of the synthesized compounds was performed on adult Danio rerio. During the experiments, the fish were kept on a diet for a test period of 96 hours, and their mortality was checked every 24, 48, 72 and 96 hours with the test compounds in each mini-aquarium containing at least 7 individuals of Danio rerio. Results. Results 1H NMR spectra confirm that the alkylation reaction occurs specifically on the sulfur atom. Thus, after analyzing LC50 data, we found that the least toxic among the studied compounds is 2-(((4-methyl-5-(octylthio)-4H-1,2,4-triazole-3-yl )methyl)thio)pyrimidine with an acute toxicity value of 49.66 mg/l. The most toxic compound is 2-(((4-methyl-5-(methylthio)-4H-1,2,4-triazole-3-yl)methyl)thio)pyrimidine with an LC50 value of 8.29 mg/l. The low toxicity of the compound 2-(((4-methyl-5-(octylthio)-4H-1,2,4-triazole-3-yl)methyl)thio)pyrimidine is most likely due to the presence of an octyl substituent, which sufficiently penetrates through biological membranes and does not have a strong toxic effect on organ systems. Furthermore, it does not accumulate but is metabolized in the cell. Conclusions. New hybrids of 1,2,4-triazole-3(2H)-yl)methyl)thiopyrimidines were obtained using the heterocyclization reaction of the intermediate carbothioamide. To reduce the indicators of acute toxicity and increase their biological activity, synthesized S-derivatives of this series were created. It was established that S-derivatives of 1,2,4-triazole-3(2H)-yl)methyl)thiopyrimidines belong to moderately toxic to low-toxic compounds according to the classification of D. R. Passino. 2-(((4-Methyl-5-(octylthio)-4H-1,2,4-triazole-3-yl)methyl)thio)pyrimidine has an acute toxicity value of 49.66 mg/l. The most toxic compound is 2-(((4-methyl-5-(methylthio)-4H-1,2,4-triazole-3-yl)methyl)thio)pyrimidine with an LC50 value of 8.29 mg/l.

Для визначення молекули, що могла б стати перспективним фармакологічним агентом, хіміки використовують уже відомі гетероциклічні основи, додаючи до них фармакологічно активні групи. Одна з таких гетероциклічних систем – 1,2,4-тріазолова основа, на базі якої вже одержали величезну кількість біологічно активних сполук. Відомо, що похідні 1,2,4-тріазолу характеризуються доволі сильним протимікробним і протигрибковим ефектами, залишаючись при цьому малотоксичними сполуками. Є дані щодо протимікробної та протигрибкової активності 5-алкілтіо-1,2,4-тріазолів. Ґрунтуючись на результатах літературного пошуку, зробили висновок, що 3-(2-бромфеніл)-5-(алкілтіо)-4-феніл-4H-1,2,4-тріазоли вивчено недостатньо. Мета роботи – синтез і дослідження протимікробної та протигрибкової активності нових 3-(2-бромфеніл)-5-(алкілтіо)-4-феніл-4H-1,2,4-тріазолів. Матеріали та методи. Як вихідну речовину застосували 5-(2-бромфеніл)-4-феніл-4H-1,2,4-тріазол-3-тіол, який синтезували за попередньо наведеними методиками. 3-(2-Бромфеніл)-5-(алкілтіо)-4-феніл-4H-1,2,4-тріазоли одержали шляхом алкілування вихідного тіолу галогеналканами (за першим методом) і додаванням хлороводневої кислоти в спиртовому середовищі з нагріванням надалі в системі мікрохвильового синтезу (за другим методом). Для вивчення протимікробної та протигрибкової активностей нових синтезованих 3-(2-бромофеніл)-5-(алкілтіо)-4-феніл-4Н-1,2,4-тріазолів використали метод серійних розведень згідно з рекомендаціями. Результати. 3-(2-Бромофеніл)-5-(алкілтіо)-4-феніл-4Н-1,2,4-тріазоли отримували двома методами: а) еквівалентну кількість галогеналкану додавали до 5-(2-бромофеніл)-4-феніл-4Н-1,2,4-тріазол-3-тіолу (I) (розчинник – 2-пропанол, у якому попередньо розчинений КОН); кип’ятили до рН = 7; б) 5-(2-бромофеніл)-4-феніл-4Н-1,2,4-тріазол-3-тіол (I) (розчинник – метанол або 1-пропанол і 10 крапель HCl) нагрівали в системі мікрохвильового синтезу Milestone Flexi Wave; умови реакції: час – 45 хвилин, температура – 150 °C, тиск – 14,4 бар, ΔMW ≈ 200 Вт. Повноту реакції визначали за допомогою газового хроматографа Agilent 7890B з мас-спектрометричним детектором 5977B. Дослідили протимікробну та протигрибкову активності 3-(2-бромофеніл)-5-(алкілтіо)-4-феніл-4Н-1,2,4-тріазолів. Найактивніша сполука з протигрибковим і протимікробним ефектами – IIi. Речовини IIa–IIe мають помірну протимікробну дію. Висновки. Нові 3-(2-бромофеніл)-5-(алкілтіо)-4-феніл-4Н-1,2,4-тріазоли синтезовано двома методами. Оцінювали протимікробну та протигрибкову активності одержаних сполук. Найактивніша – 3-(2-бромофеніл)-5-(децилтіо)-4-феніл-4Н-1,2,4-тріазол (IIi). Сформулювали висновки щодо залежності «структура – протимікробна та протигрибкова дії»: зміна децильного радикала на пентильний у молекулі 3-(2-бромофеніл)-5-(алкілтіо)-4-феніл-4Н-1,2,4-тріазолу зменшує протигрибкову активність; антимікробний ефект посилюється зі збільшенням довжини вуглецевого радикала.

The genus Salvia L. has more than 900 species distributed throughout the globe. 21 species are growing in Ukraine. All species of this genus have essential oils. Salvia officinalis and Salvia sclarea have been used in the culture and are widely used in medical practice. The chemical composition of other species of sage and the possibility of their use in pharmaceutical and medical practice are almost not studied. Taking into account the results of chemotaxonomic studies of species of the flora genus of Ukraine, their prevalence and prospects for introduction into the culture, for further studies were selected raw materials of S. grandiflora, S. pratensis and S. verticillata. The aim. The aim of the study was to conduct a chromato-mass spectrometric study of the aboveground organs of S. grandiflora L., S. pratensis L. and S. verticillata L. to establish the prospects for the use of raw materials of these species in medical and pharmaceutical practice. Materials and methods. The objects of the study were leaves of S. officinalis, leaves, stems and flowers of S. grandiflora, S. pratensis and S. verticillata, which were harvested on the basis of the botanical garden of Ivan Franko National University of Lviv. The research of volatile substances in the objects of the research was carried out by the method of GC-MS on the basis of the Department of Natural Sciences for Foreign Students and Toxicological Chemistry of Zaporizhia State Medical University. Results. As a result of the study, 243 substances were found in the objects of the study, of which 149 were identified. 77 substances were found in the leaves of S. officinalis, 80, 26 and 63 substances in the leaves, stems and flowers of S. grandiflora, respectively, in the leaves , stems and flowers of S. pratensis – 28, 30 and 48 substances, respectively, in leaves, stems and flowers of S. verticillata – 39, 22 and 39 substances, respectively. Dominant compounds among substances of terpenoid nature are: cyclofenchene, camphene, 1,8-cineole, α-thujone, β-thujone, camphor borneol, caryophyllene, humulene, viridiflorol, sabinene, pyranone, β-pinene, phytol, kolavenol, β-copaen, loliolide, pseudolimonene and spatulenol. Among the dominant substances, 8 were detected for the first time in these species: cyclofenchene, viridiflorol, sabinene, pyranone, phytol, kolavenol, loliolide and pseudolimonene. Conclusions. The leaves of S. officinalis, leaves, stems and flowers of S. grandiflora, S. pratensis and S. verticillata of the flora of Ukraine were studied by chromato-mass spectrometric method. As a result of the study, 243 substances were identified, of which 149 were identified. Promising raw materials containing terpene compounds for S. grandiflora there are leaves, and for S. pratensis and S. verticillata – flowers, so they are promising agents for introduction into pharmaceutical practice

The aim of the work was chromato-mass-spectroscopic research of chemical composition of Elaeagnus angustifolia L. fruits and leaves and identifying further prospects for the use of this plant in medicine. Materials and methods. Raw materials of Elaeagnus angustifolia L. were selected as objects of study. The tincture was obtained by maceration and the raw material was extracted with methyl alcohol at room temperature for 10 days according to the method of making tinctures. The study of the chemical composition of Elaeagnus angustifolia L. was carried out using gas chromatograph Agilent 7890B GC System (Agilent, Santa Clara, CA, USA) with mass spectrometric detector Agilent 5977 BGC/MSD (Agilent, Santa Clara, CA, USA) and chromatographic column DB-5ms (30 m × 250 mkm × 0,25 mkm). Results. 23 compounds (1 in the isomeric state) in fruits and 20 compounds (2 in the isomeric state) in the leaf of Elaeagnus angustifolia L. were identified. The main components of fruits were sitosterol (phytosterols) – 12.53 %, propyl acetate (esters of carboxylic acids) – 12.60 %, chamazulene (terpenes) – 11.97 % and palmitic acid (fatty acids) – 8.28 %. The main component of leaves were sitosterol (phytosterols) – 17.57 %, 1-(2-hydroxy-5-methylphenyl)-ethanone (ketone) – 8.35 %, phytol (terpenes) – 6.10 %. It is known from the literature that chamazulene has antioxidant, antinociceptive, cytotoxic activity. Sitosterol has anti-inflammatory and antidiabetic activity. Hexadecanoic (palmitic) acid has antimicrobial, antidiabetic and antioxidant properties. Phytol is characterized by a wide range of biological action – antimicrobial, antinociceptive, anti-inflammatory, antioxidant and cytotoxic. Conclusions. Based on the above, the olive can be considered as a source of antimicrobial, antinociceptive, anti-inflammatory, antioxidant, antidiabetic and cytotoxic drugs.