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

Foot fungus (Candida, molds, dermatophytes) is a fairly common problem. According to the WHO, one-fifth of the world’s population is affected by fungal skin diseases. The prevalence of mycosis of the feet, which affects every second person, is especially increasing. Such a pathology can appear quite unexpectedly and at an inappropriate time. Today, Ukraine is under aggressive pressure from its northern neighbor, and military personnel are not only constantly at risk of receiving combat injuries and wounds, but also due to active hostilities, they may not have access to the necessary hygiene products, get cold, overheat in the sun, or not have time to change their clothes in time. and shoes. The reality is the absence or delay of treatment; the disease progresses and can spread quickly. If mycosis has appeared in one soldier, it can quickly affect others. Therefore, the problem of providing medical and pharmaceutical care is an urgent issue today. Expanding the assortment of drugs with the above action will ensure the needs of the Armed Forces and civilian patients with this dermatological pathology. It will be able to optimize antifungal therapy regimens. For quite a long time, 1,2,4-triazole derivatives have been a promising class of organic compounds that attract the attention of scientists from various fields. It has been proven that 2-(((3-(2-fluorophenyl)-5-thio-4H-1,2,4-triazole-4-yl)imino)methyl)phenol has high antifungal activity. A potential medicinal product based on this medicinal substance can be used for the treatment of various dermatological diseases. To continue the creation of new effective dosage forms for the effective therapy of mycosis of the feet, the urgent task of today is the development of an express, accurate, reliable, and affordable method of quantitative determination of the substance under study. The aim of the work is to develop an express, sensitive and easy-to-implement UV-method for the quantitative determination of 2-(((3-(2-fluorophenyl)-5-thio-4H-1,2,4-triazole-4-yl)imino)methyl)phenol. Materials and methods. The research object is a working standard sample of 2-(((3-(2-fluorophenyl)-5-thio-4H-1,2,4-triazole-4-yl)imino)methyl)phenol provided by NUNVF, LLC “Brovapharma” according to the “Research and production technological regulations for the production of 2-(((3-(2-fluorophenyl)-5-thio-4H-1,2,4-triazol-4-yl)imino)methyl)phenol” developed based on scientific developed by the Ukrainian Military Medical Academy in conjunction with the National Military Medical Clinical Center “Main Military Clinical Hospital” (term of validity of the regulations until 12/31/2034). Isopropanol of grade “chemically pure” was used as a solvent. Analytical equipment: spectrophotometer Specord 200, electronic scales Radwag XA 210.4Y, class A measuring vessels. Results. An express, eco-friendly spectrophotometric method was developed for the quantification of 2-(((3-(2-fluorophenyl)-5-thio-4H-1,2,4-triazole-4-yl)imino)methyl)phenol in isopropanol area, having analytically maximum at 310 nm. The studied solutions are stable for 30 minutes. The analytical technique is linear in the range of concentrations 0.440–0.754 mg/100 ml (70–130 %). The detection and quantification limits were 5.80 % and 15.70 % respectively. The score was 0.76, according to the “greenness” icon of the analytical technique, using the tools AGREE. The prediction of the total uncertainty of the results of the developed method is 1.70 % (max∆As 2.00 %). The proposed method is relevant according to the requirements of the State Pharmacopoeia of Ukraine. Conclusions. Pharmaceutical development, introduction into industrial production and further prescribing by dermatovenerologists of an effective, safe, and harmless medicinal product will help to expand the range and reduce the level of high import dependence of the domestic market of medicinal products, which will create a more complete and balanced system of medicinal supply in Ukraine and optimize antifungal therapy schemes.

In Ukraine, there are about 100 thousand people with epilepsy. Gabapentin is an effective antiepileptic agent for oral use, presented in capsules of different dosages from different manufacturers. Therefore, the urgent task of pharmaceutical analysis today is the development of highly accurate, reliable, affordable and fast methods of quantitative determination. The aim of the work is to develop a spectrophotometric technique for the quantitative determination of gabapentin in capsules based on the reaction with diazole red 2J in compliance with the SPhU. Material and methods. As reagent and solvent, diazole red 2J of AR grade, acetone of AR grade and purified water was used. Analytical equipment: Specord 200 and Specord 250 Plus spectrophotometers, ABT-120-5DM and Radwag XA 210.4Y electronic scales, Elmasonic E 60H and Sonorex Digitec DT100H ultrasonic baths, measuring glassware of A class. Results. A simple, accurate and eco-friendly colourimetric method was developed for the quantification of gabapentin in capsules. The method was based on the reaction of gabapentin with diazole red 2J to give a coloured product having analytical maxima at 390 nm. Factors affecting colour development and stability were optimized and incorporated into the procedure. Regression analysis of Beer's plot showed a good correlation (not less than 0.999) in a concentration range of 2.10 – 3.64 mg/100 ml. The detection and quantification limits were 2.25 % and 6.19 %, respectively. The intra- and inter-laboratory precision demonstrates and reflects no interference by the capsule additives and confirms the reproducibility of the method in the selected concentration range. The prediction of the total uncertainty of the results of the developed method is calculated and displayed to assess the correctness of the reproduction of the method. Conclusions. It has been proven that the developed method meets the requirements of the State Pharmacopoeia of Ukraine and allows to perform the correct quality control of medicinal products.

Ischemia/reperfusion injury (IRI) is a common damage due to the restoration of blood flow following an ischemic injury. Its pathogenesis is mainly linked to the production of reactive oxygen species (ROS), which sustain cell damage and promote cell death. The tardigrade damage suppressor protein (Dsup) is a DNA-binding protein that enables tardigrades to tolerate stress conditions, including oxidative stress. We investigated the ability of the Dsup to protect human cells from IRI, using an in vitro model of hypoxia and reoxygenation. We exposed HEK293TT cells transfected with the Dsup to hypoxic injury and analyzed cell viability, oxidative stress, expression of antioxidant proteins using functional assays, and a proteomic approach to dissect the molecular mechanisms modulated by the Dsup. Dsup expression significantly enhanced cell survival following hypoxia-reoxygenation and markedly reduced intracellular ROS levels. Proteomic and Western blot analyses revealed a significant upregulation of antioxidant enzymes in Dsup-expressing cells. Furthermore, the Dsup modulated autophagy and key stress-related pathways, including the MAPK cascade. This study demonstrates that the Dsup protects human cells from IRI by reducing oxidative stress and modulating key cytoprotective pathways. Our results establish the Dsup as a promising candidate for future therapeutic applications against IRI, meriting further exploration in in vivo models.

За статистикою, черепно-мозкові травми часто стають причиною інвалідності cеред населення. Вибір лікарських засобів при травматичних ушкодженнях головного мозку – одна з найскладніших проблем у комплексі лікування таких хворих. Адемол (1-адамантилетилокси-3-морфоліно-2-пропанол гідрохлорид) – перспективна лікарська речовина, що має позитивний терапевтичний ефект захисної дії на мозок при його ураженні, може міститися в лікарських препаратах різного дозування. Тому актуальним завданням є розроблення точної, достовірної, доступної та швидкої методики кількісного визначення адемолу. Мета роботи – вивчення оптимальних умов перебігу реакції «адемол – бромкрезоловий зелений» і розроблення експресної, чутливої та простої для виконання методики кількісного визначення адемолу. Матеріали та методи. Як реактив і розчинник використовували бромкрезоловий зелений (БКЗ) кваліфікації «х. ч.», ацетон кваліфікації «ч. д. а.». Аналітичне обладнання: спектрофотометр Specord 200, ваги електронні АВТ-120-5DM, ультразвукова баня Elmasonic E 60H, мірний посуд класу А. Результати. Розробили нову методику кількісного визначення адемолу спектрофотометричним методом. Вивчили оптимальні умови перебігу реакції між речовиною, що визначали, та реагентом, а також встановили межі концентрацій, у яких спостерігали підпорядкованість основному закону світлопоглинання. Здійснили прогноз повної невизначеності результатів цього методу кількісного визначення для оцінювання коректності відтворення розробленої методики в інших лабораторіях. Запропонована методика є актуальною за вимогами Державної фармакопеї України. Висновки. Згідно з експериментальними даними, методика кількісного визначення адемолу може бути коректно відтворена та придатна для використання.

Obesity is a global epidemic associated with chronic inflammation, oxidative stress, and metabolic disorders. Bariatric surgery is a highly effective intervention for sustained weight loss and the improvement of obesity-related comorbidities. However, post-surgery nutritional deficiencies, including vitamin E, remain a concern. This study investigates the role of single-nucleotide polymorphisms (SNPs) in genes related to vitamin E transport and bioavailability in determining vitamin E levels post bariatric surgery. A cohort of 140 patients with obesity undergoing bariatric surgery was analyzed. Serum vitamin E levels were measured before and one year after surgery, and SNPs in genes associated with vitamin E transport and metabolism were genotyped using PCR, DHPLC, and sequencing methods. Associations between SNPs, haplotypes, and vitamin E levels were statistically evaluated. Significant associations were observed between the APOE rs7412 SNP and serum vitamin E levels. The rare T allele was linked to lower vitamin E levels post surgery, with an increased frequency in patients with severe deficiency (<11.6 μmol/L). Haplotype analysis of APOE revealed that the ε2 haplotype (T-T) was strongly associated with vitamin E deficiency. Other SNPs, including CD36 rs1761667, SCARB1 rs4238001, and ABCA1 rs4149314, were also linked to changes in vitamin E levels, suggesting that an impaired bioavailability and transport can be the reason for low vitamin E levels post surgery. Genetic polymorphisms in APOE, CD36, SCARB1, and ABCA1 significantly influence vitamin E status after bariatric surgery. These findings highlight the importance of personalized supplementation strategies considering patients’ genetic profiles to mitigate the risk of vitamin E deficiency and related complications.