http://dspace.zsmu.edu.ua/handle/123456789/279 Wed, 26 Aug 2026 17:04:47 GMT 2026-08-26T17:04:47Z http://dspace.zsmu.edu.ua/handle/123456789/25713 Название: Orotic Acid-1,2,4-Triazole Hybrids as Potential MMP-2,9 Modulating Wound-Healing Agents: Synthesis, Molecular Docking and Biological Evaluation Авторы: Karpenko, Yu. V.; Parchenko, V. V.; Kucherenko, L. I.; Chetvertak, T.; Bihdan, O. A.; Pukhalska, I. O.; Roik, O.; Safronova, D. M.; Meladze, I. N.; Bushueva, I. V.; Карпенко, Юрій Вікторович; Парченко, Володимир Володимирович; Кучеренко, Людмила Іванівна; Бігдан, Олексій Антонович; Пухальська, Ірина Олександрівна; Сафронова, Дар'я Михайлівна; Меладзе, Ігор Нисанович; Бушуєва, Інна Володимирівна Аннотация: The matrix metalloproteinases MMP-2 and MMP-9 are involved in extracellular matrix remodeling, inflammatory response, and tissue remodeling, and overactivity of certain metalloproteinases may also contribute to chronic wound healing. The aim of this work was to synthesize novel hybrid derivatives of orotic acid and 1,2,4-triazole and investigate them as potential modulators of MMP-2/MMP-9. The structure of the compounds was confirmed by 1H, 13C NMR spectroscopy, LC–MS, and elemental analysis. Pharmacokinetic properties were calculated using SwissADME, and enzyme interactions were characterized using molecular docking strategies, protein–ligand contact analysis, and 100 ns molecular dynamics. The inhibitory effect was also assessed in vitro by fluorimetry at a concentration of 10 μM. The compounds had an acceptable drug-like profile, without violations of Lipinski’s rule and PAINS warnings. The highest affinity for MMP-9 was also found for the three target proteins 17, 19 and 13, which showed values of −9.65, −9.47 and −9.17 kcal/mol, respectively, compared to −8.37 kcal/mol for NNGH. Dynamic molecular analysis confirmed the stability of the 13–MMP-9 complex. Compounds 17 and 13 inhibited MMP-9 by 94.2 ± 4.8% and 85.2 ± 3.8%, respectively, with little effect on MMP-2, whereas compound 19 showed balanced inhibition of MMP-2 and MMP-9 by 74.2 ± 4.4% and 79.2 ± 2.8%, respectively. The results identified 13 and 17 as potential compounds with preferential effects on MMP-9, and 19 as a possible dual inhibitor for wound healing activity studies. Thu, 01 Jan 2026 00:00:00 GMT http://dspace.zsmu.edu.ua/handle/123456789/25713 2026-01-01T00:00:00Z http://dspace.zsmu.edu.ua/handle/123456789/25678 Название: Spectrophotometric determination of antiradical potential of some 5-ylidene derivatives of rhodanine with a benzothiazole moiety in the molecules Авторы: Mosula, L. M.; Mosula, V. S.; Mazur, V. V.; Karpenko, Y. V.; Карпенко, Юрій Вікторович Аннотация: This study evaluates the antiradical potential of hybrid systems based on the benzothiazolerhodanine scaffold, the synthesis of which was previously reported. Such heterocycles are promising objects in medicinal chemistry due to their broad spectrum of biological activities and the possibility of versatile functional substitution. Establishing structure– activity relationships is essential for the rational design of potent antioxidants. Preliminary DPPH screening of N-(4-oxo-2-thioxothiazolidin-3-yl)-2-(2-oxobenzo[d]thiazol- 3(2H)-yl)acetamide and its 5-ylidene derivatives established that only the unsubstituted core heterocycle exhibits high activity comparable to ascorbic acid. Substitution at the 5-position of the rhodanine ring results in a decrease or loss of free radical scavenging activity. Among the derivatives, the compound bearing a 2,3-dichlorobenzylidene fragment exhibited the highest activity (62.85% at 2.0 mM), whereas other substituted benzylidene or isatinylidene derivatives displayed lower levels of inhibition. Modification of the 5-ylidene moiety appears to deactivate direct radical reactions. The observed effects are attributed to a complex interplay of electronic, thermodynamic, and delocalization factors, alongside limited steric accessibility of the reactive centers. Quantum chemical calculations using density functional theory for the most active heterocycle with a 5-unsubstituted rhodanine scaffold indicate that SPLET is the prevailing mechanism in methanol and substantiate its high radical scavenging activity in the DPPH test. The HAT pathway remains a plausible alternative under certain conditions or for different radicals, but it appears less favorable in MeOH. Similarly, SET-PT is thermodynamically possible but not initially favorable due to the higher ionization energy of the neutral molecule. Such synergy of approaches outlines the structure–activity relationship and provides a foundation for the rational design and targeted synthesis of the most promising agents for subsequent in vivo studies. Thu, 01 Jan 2026 00:00:00 GMT http://dspace.zsmu.edu.ua/handle/123456789/25678 2026-01-01T00:00:00Z http://dspace.zsmu.edu.ua/handle/123456789/25616 Название: Organ-Specific Phytochemical Profiles, Wound-Healing and Hemostatic Activities of Symphytum officinale Aerial Parts and Roots with Differential Pyrrolizidine Alkaloid Content Авторы: Dolgošev, G.; Kolesnyk, Yu. M.; Hancheva, O. V.; Panasenko, O. I.; Kaplaushenko, A. H.; Shcherbyna, R. O.; Jakštas, V.; Žvikas, V.; Laidmäe, I.; Heinämäki, J.; Koshovyi, O.; Raal, A.; Колесник, Юрій Михайлович; Ганчева, Ольга Вікторівна; Панасенко, Олександр Іванович; Каплаушенко, Андрій Григорович; Щербина, Роман Олександрович Аннотация: Wound healing is a complex biological process involving inflammation, hemostasis, and tissue regeneration, and its impairment may delay recovery and lead to clinical complications. Medicinal plants have long been used in traditional medicine to support wound repair and control bleeding. Among these, Symphytum officinale L. (comfrey) is widely used in European traditional medicine for the treatment of wounds, fractures, and soft tissue injuries. However, the pharmacological basis of these effects and the contribution of different plant organs remain insufficiently understood. The aim of this study was to characterize the phytochemical composition of extracts obtained from different organs of S. officinale and to evaluate their hemostatic and wound-healing activities in vivo, in order to identify the most active plant parts. Extracts from the roots, leaves, and flowers of S. officinale were prepared using solvents of different polarity. Phytochemical composition was analyzed by spectrophotometric assays and UPLC–MS/MS. Hemostatic and wound-healing activities were evaluated in vivo in rats, and cytological analysis of wound exudate was performed. Distinct organ-specific differences in phytochemical composition were observed, with leaf and flower extracts richer in phenolic compounds and amino acids, while root extracts contained higher levels of pyrrolizidine alkaloids. Leaf (S7) and flower (S13) extracts showed the strongest biological activity. S13 accelerated wound healing, achieving complete wound closure by day 10 compared with day 12 in the reference group, while S7 exhibited the most pronounced hemostatic effect, reducing bleeding cessation time to 44.3 s compared with 64.1 s for the reference preparation and 144.3 s for the control group. Cytological analysis indicated reduced inflammation and enhanced fibroblast activity. The findings support the traditional use of S. officinale in wound treatment and highlight the importance of organ-specific phytochemical composition. Aerial parts showed strong wound-healing and hemostatic effects, suggesting their relevance alongside the traditionally used root and supporting the involvement of multiple constituents in the observed biological activity. The study provides new insights into the organ-specific phytochemical composition and biological activity of S. officinale, thereby supporting further research on the therapeutic potential of its aerial parts. Thu, 01 Jan 2026 00:00:00 GMT http://dspace.zsmu.edu.ua/handle/123456789/25616 2026-01-01T00:00:00Z http://dspace.zsmu.edu.ua/handle/123456789/25575 Название: Modern approaches to the synthesis and biological screening of 1,2,4-triazole-3-thiol derivatives (literature review) Авторы: Kalchenko, V. V.; Shcherbyna, R. O.; Кальченко, В. В.; Щербина, Роман Олександрович Аннотация: Aim. To systematize and critically analyze current scientific publications on the synthesis and biological screening of 1,2,4-triazole-3-thiol derivatives and to summarize the relationship between their structure and pharmacological activity. Special attention was paid to the prospects of using these compounds as scaffolds for the development of new biologically active substances and potential active pharmaceutical ingredients. Materials and methods. The review included publications by domestic and foreign authors devoted to methods for the synthesis, chemical modification, and biological evaluation of 1,2,4-triazole-3-thiol derivatives. Literature retrieval was carried out in the Scopus, Web of Science, PubMed, and Google Scholar databases using Ukrainian- and English-language keywords related to 1,2,4-triazoles, triazole-3-thiols, synthesis, and biological activity. The selected sources were analyzed by systematization, comparative assessment, and generalization of data on synthetic approaches, thiol-group transformations, directions of structural modification, and the results of pharmacological screening. Мета роботи – систематизувати та критично проаналізувати сучасні наукові публікації, присвячені синтезу та біологічному скринінгу похідних 1,2,4-тріазол-3-тіолу, а також узагальнити відомості про взаємозв’язок між їхньою будовою та фармакологічною активністю. Окрему увагу приділено оцінюванню перспектив використання цих сполук як молекулярних платформ для створення нових біологічно активних речовин і потенційних активних фармацевтичних інгредієнтів. Матеріали і методи. До огляду включено публікації вітчизняних і зарубіжних авторів, присвячені методам синтезу, хімічній модифікації та біологічному оцінюванню похідних 1,2,4-тріазол-3-тіолу. Пошук літератури здійснювали в базах даних Scopus, Web of Science, PubMed і Google Scholar. Використовували україномовні та англомовні ключові слова, пов’язані з 1,2,4-тріазолами, тріазол-3-тіолами, синтезом і біологічною активністю. Відібрані джерела проаналізовано методами систематизації, порівняльного оцінювання й узагальнення даних щодо синтетичних підходів, перетворень за участю тіольної групи, напрямів структурної модифікації та результатів фармакологічного скринінгу. Thu, 01 Jan 2026 00:00:00 GMT http://dspace.zsmu.edu.ua/handle/123456789/25575 2026-01-01T00:00:00Z