The aim of work: to systematize current literature data on the mechanisms of antioxidant action and prospects for structural improvement of thiazole-containing compounds, which will allow us to outline key directions of further research in this area. Materials and methods: The information-analytical framework of this study was established through a systematic search of scientific publications in the international databases Scopus, Web of Science Core Collection, PubMed / MEDLINE, and Google Scholar, covering the period 2011–2026, with particular emphasis on studies published within the last five years. Full-text original research articles reporting quantitative evaluation of antioxidant activity, as well as studies involving SAR/QSAR analysis, were included in the review. Data synthesis was performed using systematic, comparative, and content analysis approaches to identify structure – activity relationships and to define prospects for the structural optimization of thiazole-containing compounds in accordance with current standards for review articles. Results. Antioxidants play an important role in the prevention and treatment of diseases associated with oxidative stress, including cardiovascular, neurodegenerative and oncological pathologies. Despite a wide range of natural and synthetic antioxidants, their therapeutic efficacy is limited due to low bioavailability, instability in biological media and possible toxicity. Thiazole-containing heterocyclic compounds have shown significant potential as antioxidants due to their ability to scavenge free radicals, chelate metals and stabilize reactive oxygen species. This review summarizes current data on the synthesis, mechanisms of action, methods for assessing antioxidant activity and prospects for structural improvement of thiazole-containing heterocycles. A critical analysis of existing approaches is proposed and key directions for further research using multidisciplinary strategies are identified. Conclusions. Thiazole-containing heterocycles form a wide range of structural systems that differ in electronic structure and mechanisms of antioxidant action. In addition, increased antioxidant activity is achieved through the introduction of electron-donating substituents, phenolic fragments and combination with other heterocyclic systems, which allows the creation of multifunctional molecules with potentially high therapeutic value.
The aim of the article is to investigate the local irritant effect on the skin and conjunctiva of the eyes of the amber-based oil complex TM IL SAV AMBER and to analyze its sensitizing activity in vivo. Materials and methods. A series of chronic experiments of different durations (48 hours, 14 days and 4 weeks) were used to study the local irritant effect of the drug in vivo (on white sexually mature mice, 2 groups of animals, one of which was a control, n = 20 – method of skin applications; and on white-colored or white-spotted guinea pigs weighing 300–400 g, 2 groups of animals, one of which was a control, n = 10 – conjunctival test) and to study the sensitizing effect of the drug in vivo (on white-colored guinea pigs weighing 300–400 g, 4 groups of animals, two of which were control, n = 20 – method of repeated skin applications). Results. Studies of the skin irritation effect of the drug in mice showed that dermal applications of the studied drug for 14 days did not cause signs of inflammation and damage – redness, edema, rashes and ulceration. The general behavior of the experimental animals (mobility, appetite, coat) did not differ from that of the control group. The conjunctival test did not reveal hyperemia and edema of the conjunctiva, sclera and lacrimal duct, and also did not cause immediate-type hypersensitivity reactions. The study of the sensitization properties of the studied drug using dermal applications did not reveal immediate-type and delayed-type hypersensitivity reactions in experimental animals in vivo. Conclusions. The oil complex based on amber TM IL SAV AMBER did not affect general behavior, did not cause local irritation, and did not exhibit sensitizing activity in the studied animals in vivo.
In recent years, increasing attention has been paid to natural compounds as potential agents due to their broad spectrum of biological activities. Plant-derived antioxidants with anti-inflammatory properties are of particular interest, as they may suppress pathological pathways. Therefore, the search for novel natural compounds capable of attenuating inflammation remains a promising area of biomedical research. The aim of work was to evaluate the anti-inflammatory activity of a blackberry thick fruit extract using an in vivo model and molecular docking. Materials and methods. The object of study was a blackberry thick fruit extract. Molecular docking was performed using AutoDockTools 1.5.6. Anti-inflammatory effect was assessed by the model of carrageenan-induced paw edema in rats. Results. Theoretical assessment of the anti-inflammatory activity of the blackberry fruit extract showed that blackberry anthocyanins as cyanidin-3-glucoside, cyanidin-3-(3”-malonyl glycoside) and cyanidin-3-xyloside blocked highly selective three out four pro-inflammatory targets as cyclooxygenase-2 (COX-2), phospholipase A2 and 5-lipooxygenes (5-LOX), whereas, сyanidin-3,3’-diglucoside and cyanidin-3-rutinoside highly selective blocked two out of four targets as phospholipase A2 and 5-LOX. There was not found any high selective inhibitor among anthocyanins of nuclear factor kB (NF-kB), whereas cyanidin-3-xyloside showed a moderate selectivity. Experimental studies have shown the blackberry fruit thick extract at a dose of 60.0 mg/kg and 30.0 mg/kg significantly reduces edema after 1, 2, 3 and 4 hours compared to the control group. Conclusions. Theoretical and experimental research of anti-inflammatory properties of blackberry fruit extract using molecular docking analysis and in vivo model of carrageenan-induced paw edema in rats, respectively, has been conducted. Theoretical results have shown blackberry anthocyanins possessed ability to inhibit all crucial pro-inflammatory targets as COX-2, phospholipase A2, 5-LOX and Nf-kB. Experimental results have demonstrated that blackberry thick fruit extract at doses of 60.0 mg/kg and 30.0 mg/kg possessed the ability to significantly inhibit inflammation at all stages of the carrageenan-induced paw edema model.
Aim of the study – experimental substantiation of the possibility of quantitative determination of fluoride ions in a model heterogeneous cosmetic system in the form of toothpaste using direct potentiometry with a fluoride-selective electrode. Materials and methods. The study was carried out using direct potentiometry with a fluoride-selective electrode. A TISAB buffer solution was applied to stabilize the ionic strength of the medium and to minimize the influence of matrix components. Sample preparation included dissolving a weighed portion of toothpaste in distilled water followed by the addition of an equal volume of buffer solution. Calibration of the electrode system was performed using standard sodium fluoride solutions. The object of the study was a heterogeneous cosmetic system in the form of toothpaste containing abrasive components, moisturizers, surfactants, a polymer thickener and sodium fluoride as a source of fluoride ions. Results. The obtained results demonstrated that the model toothpaste sample is characterized by a stable heterogeneous structure and a uniform distribution of fluoride ions. According to the potentiometric measurements, the average fluoride content in the studied sample was 985.0 ± 5.2 ppm, which complies with regulatory requirements for fluoride-containing toothpastes intended for daily use. The low variability of the obtained values indicates good reproducibility of the method and a minimal influence of the multicomponent toothpaste matrix on the analytical results. Conclusions. The results confirm the applicability of the direct potentiometric method using a fluoride-selective electrode in combination with a TISAB buffer solution for quantitative determination of fluoride in multicomponent heterogeneous cosmetic systems without prior destruction of the product matrix. The proposed approach can be used for analytical quality control of fluoride-containing toothpastes during product development, manufacturing and standardization of oral hygiene cosmetic products.
The modern concept of treatment of infectious urogenital lesions is based on purposeful etiotropic and pathogenetically justified prescription of effective drugs. At the same time, the correct choice of medical tactics and appropriate pharmacotherapeutic agents, considering the specific features of the pathology, becomes of paramount importance. For the successful implementation of this direction, the use of active pharmaceutical ingredients is promising, which, along with a wide range of antibacterial and antimycotic effects and a minimum level of toxicity, does not cause the appearance of resistant strains of sexually transmitted pathogens. The creation of effective, complementary and accessible for practical medicine vaginal dosage forms based on innovative compounds containing halide substituents will increase the efficiency of venereal care and improve the reproductive health of the population of Ukraine. The aim of this work is to determine the optimal amount of ciminal in vaginal suppository compositions. Materials and methods. The effect of the mass fraction of ciminal in vaginal suppositories was evaluated on model polyethylene oxide carrier compositions with the addition of 0.05 ml of dimexide, which, according to the literature, increases its solubility and degree of antimicrobial activity. The amount of ciminal in the studied vaginal dosage forms was 0.01–0.15 g, taking into account the average suppository weight of 3 g. The study was conducted using a mathematical plan of one-factor analysis of variance with repeated observations. As an optimization parameter, the level of specific activity of experimental suppository masses was used, which was evaluated by diffusion into agar against gram-negative Pseudomonas aeruginosa and Candida albicans fungi, the lesion of which urethral pathways is a serious clinical problem, considering their prevalence and high resistance to pharmacotherapy. Results. It was found that the studied vaginal suppositories containing different amounts of ciminal exhibit a sufficiently high level of antibacterial and antimycotic activity, the level of which increases with increasing dose of the active substance. Conclusions. Studies of the antimicrobial activity of suppository compositions with ciminal prove that their effectiveness is statistically significantly influenced by the mass fraction of the active pharmaceutical ingredient. It was found that the optimal level of antimicrobial activity of the soft vaginal dosage form provides a mass fraction of ciminal in an amount of 0.15 g, taking into account the average mass of suppositories of 3 g.
The need to create new sublingual tablets for the treatment of diseases of the oral mucosa is due to the insufficient number of domestic drugs on the pharmaceutical market. Therefore, the development of tablets based on thiotriazolin and decamethoxin, as a potentially new drug, for the treatment of diseases and the sanitation of the oral cavity in pathological conditions such as gingivitis, stomatitis, etc. is an urgent task for pharmacy and medicine. The aim of the work is to develop a rational tablet composition, justify the choice of excipients in its composition and analyze the dosage form according to pharmaco-technological indicators in accordance with the requirements of the State Pharmacopoeia of Ukraine. Materials and methods. Active substances – thiotriazolin and decamethoxin; excipients (based on microcrystalline cellulose, granulated sugars, glidants, lubricants and baking powders). During the study powder mixtures were tested for bulk density after compaction, fluidity and angle of natural slope. Further, the compressed series of tablets were tested for strength, disintegration and abrasion in accordance with the requirements of the State Pharmacopoeia of Ukraine. Results. As a result of the research, we found that the manufactured series of tablets when assessing their pharmacokinetic properties do not have stable established indicators that are regulated by the State Pharmacopoeia of Ukraine. Therefore, an analysis of foreign and domestic literature sources was conducted regarding tablets containing decamethoxin as the active ingredient. Also, in the process of experimental research, a new composition of tablets based on thiotriazolin with decamethoxin by direct compression has already been developed and a comparative analysis of their pharmacokinetic properties has been conducted. Conclusions. During the work, the choice of excipients was justified, the possibility of obtaining tablets by direct compression was experimentally confirmed, and their optimal composition was developed, which meets the basic requirements of the State Pharmacopoeia of Ukraine.
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. Results. The analysis showed that 1,2,4-triazole-3-thiol derivatives represent an important class of heterocyclic compounds with broad possibilities for purposeful structural modification and a wide spectrum of biological effects. Their synthesis is most often based on cyclization reactions involving thiosemicarbazides, hydrazides, isothiocyanates, and related intermediates, whereas the efficiency of the process depends on solvent, temperature, catalyst, and the nature of substituents. The summarized literature indicates that these compounds may exhibit antimicrobial, antifungal, antiviral, antioxidant, anti-inflammatory, anticonvulsant, and antitumor activity, while the thiol group plays a decisive role in further S-functionalization and in shaping physicochemical and pharmacological properties. Conclusions. 1,2,4-Triazole-3-thiol derivatives are a promising platform for medicinal chemistry because their reactivity allows targeted modification and the reported biological screening results confirm the expediency of further search for new low-toxicity and pharmacologically promising compounds in this series.
The relevance of studying 1,2,4-triazole derivatives lies in the growing resistance of microorganisms and the need to develop new, effective, and safe medicines. Derivatives of 1,2,4-triazole are promising compounds in modern medical chemistry due to their wide spectrum of biological activity and ability to act on multiple targets. In addition to pharmacology, these compounds have significant potential in materials science, catalysis, “green chemistry” and as agents with wound-healing activity. The aim of the work is to conduct a systematic review of the literature based on data from international scientometric databases, to summarise and critically evaluate data on the wound-healing activity, synthesis, physicochemical properties, biological activity and safety of 1,2,4-triazole derivatives; to identify key structure-activity relationships and the most suitable pharmaceutical platforms for the local treatment of wound processes. Materials and methods. Scientific publications selected as a result of a systematic search in the databases PubMed / MEDLINE, Scopus, Web of Science, Embase, Cochrane Library and Google Scholar served as research materials. The work uses search, analytical, descriptive methods, as well as methods of comparison and generalization of the obtained data. Results. Based on the study of available information and conducting an information-patent search, it was established that compounds containing the 1,2,4-triazole group exhibit a wide range of biological activity, in particular, pronounced anti-inflammatory properties mediated by inhibition of COX-1 / COX-2, LOX and modulation of pro-inflammatory cytokine levels. A number of compounds have been shown to exhibit high activity both in vitro and in vivo, in some cases surpassing reference drugs. It has been proven that potassium 5-(furan-2-yl)-4-phenyl-4H-1,2,4-triazole-3-thiolate has a complex pharmacological effect (antioxidant, anti-inflammatory and reparative), helps reduce oxidative stress, stimulates cell proliferation and collagen synthesis, thereby accelerating wound healing. Based on a review of authoritative publications, its low toxicity, demonstration of high biocompatibility, and superiority over traditional topical therapies have been established. Conclusions. A systematic review of the literature based on data from international scientometric databases has confirmed that 1,2,4-triazole derivatives are multifunctional agents for local wound therapy: they combine antimicrobial, antioxidant and anti-inflammatory effects and are capable of stimulating cell proliferation and angiogenesis; polymer systems based on them demonstrate biocompatibility and relevant physicochemical parameters for the healing of burn wounds. The key role of substitutions at 3rd and 5th positions of the triazole ring in determining bioactivity has been established; the promise of targeting the inflammatory cascade has been demonstrated.
A relevant area of pharmaceutical research is the search for new compounds capable of inhibiting free radical oxidation at various stages of the pathological process. Taking into account the prospects for practical application, particular attention of researchers is focused on carotenoids as natural bioantioxidants characterized by high biological activity and minimal toxicity. The primary function of carotenoids is to protect cellular membranes and other structural components of the cell from the damaging effects of reactive oxygen species, which determines their important role in maintaining cellular homeostasis and preventing oxidative stress. In this context, an in-depth study of analytical quality control methods, particularly the determination of the purity of the most common groups of carotenoids, is of significant interest. Aim of the study. The aim of this study was to generalize and systematize scientific data on the methods of analysis of biologically active carotenoids using high-performance liquid chromatography (HPLC), with the prospect of further application of the obtained results for the optimization of laboratory analytical methods. Materials and methods. An information search was conducted using the following scientometric databases: Scopus, Web of Science, and PubMed. Analytical, descriptive, and generalization methods were applied to achieve the objectives of the study. The research materials included data from contemporary scientific literature sources addressing the determination of purity, identification, and structural analysis of biologically active carotenoids by HPLC. Results. An analysis of available scientific literature sources was performed, focusing on approaches to the assessment of purity and structural characteristics of bioactive carotenoids using high-performance liquid chromatography. The main chromatographic parameters influencing the selectivity and sensitivity of the method, as well as sample preparation features, were considered. Conclusions. Based on the analysis of current scientific literature, examples of qualitative and quantitative determination methods for two major groups of carotenoids –carotenes and xanthophylls – using HPLC were identified. A comparative analysis of these methods was carried out, taking into account chromatographic conditions, types of stationary and mobile phases, and detection approaches, which substantiates the selection of optimal analytical conditions for further scientific and practical research.
The paper analyzes the impact of key physicochemical properties of lubricating eye drops (viscosity, pH, and surface tension) on their biocompatibility with ocular surface tissues. The necessity of a strict correlation between the quantitative characteristics of the preparations and the physiological parameters of the tear fluid is substantiated to ensure a long-term therapeutic effect in dry eye syndrome. The results obtained are of practical importance for improving production technologies and enhancing the quality of modern ophthalmic agents. The aim of this study was to evaluate the impact of the physicochemical properties of lubricating eye drops on their biocompatibility and ocular surface tolerance. Materials and methods. The study involved samples of lubricating eye drops: “Optinol 0.4 %”, “Aritear”, “Vial Sleza”, “Artelac Hypromellose”, and “Oftolik Ultra”. Density and pH were determined according to the methods of the State Pharmacopoeia of Ukraine. Surface tension was measured using the stalagmometric method and viscosity was determined by capillary viscometry. All measurements were performed at a physiological temperature of 35 °C. Statistical analysis of the results was carried out using standard statistical methods. Results. The physicochemical parameters of the lubricating eye drops “Optinol 0.4 %” and “Artelac Hypromellose” were found to optimally meet biorelevant criteria. Artelac Hypromellose was the only sample whose surface tension, both in pure form and upon model dilution, corresponds to the physiological norm, ensuring optimal spreading. While other preparations significantly lost their surface activity upon dilution, “Oftolik Ultra” and “Optinol 0.4 %” demonstrated the most stable and comfortable viscosity. Conclusions. A comparative analysis of the physicochemical properties (density, pH, surface tension, and viscosity) of five lubricating eye drop samples with different chemical natures of their active components was conducted. It was established that according to the complex of biorelevant criteria, the parameters of “Optinol 0.4 %” and “Artelac Hypromellose” are the closest to the physiological norm. It has been proven that stalagmometric and viscometric methods are effective tools for rapid quality control and predicting the biocompatibility of liquid ophthalmic agents.
Nitrogen-rich heterocyclic systems, particularly 1,2,4-triazole derivatives, are attractive sources of functionally diverse compounds and promising modifiers for electrochemical sensors. Ionometry, as a branch of potentiometric analysis, focuses on developing highly selective ion-selective electrodes (ISEs) capable of providing direct assessment of ion activity or ionogenic forms of analytes in solution. β-Estradiol is a biologically important steroid hormone; its quantification is relevant for pharmaceutical analysis. Schiff bases as membrane electroactive components represent a viable strategy to enhance sensor selectivity. The aim of the study was to create and study the electrochemical characteristics of an ISE with a plasticized membrane based on 5-(3-fluorophenyl)-4-amino-1,2,4-triazole-3-thiol with lipophilic ionogenic additives of various nature – tetraoctylammonium bromide (TOABr) and sodium tetraphenylborate (NaB(C6H5)4, NaBPh). Materials and methods. The electroactive Schiff base was synthesized by condensation of 2-hydroxy-5-(phenyldiazenyl)benzaldehyde with 5-(3-fluorophenyl)-4-amino-1,2,4-triazole-3-thiol in n-butanol (2 h reflux, 12 h standing), followed by purification (DMF recrystallization) and structural confirmation by elemental analysis and 1H NMR (DMSO-d6, 400 MHz). A PVC membrane (0.2 g) was prepared containing 2 wt.% electroactive compound, 0.5 wt.% ionogenic additives (NaBPh or TOABr), polyvinyl chloride (PVC; one-third of the mass), and nitrophenyloctyl ether (two-thirds) as plasticizer, using tetrahydrofuran as the casting solvent. Potentiometric measurements were performed at 20–25 °C (Ezodo PL-700PV) versus an Ag/AgCl reference electrode. Calibration was carried out in the 10-2–10-4 M β-estradiol range (1000–10 ppm) with reproducibility control every 2 h. Results. The use of plasticized PVC membranes and a solid-contact configuration was justified to improve potential stability and minimize drift. The presence of azo and azomethine fragments in the modifier implies a dual-pathway electroanalytical process. A mathematical model incorporating diffusion supply and electrode surface coverage by reduction products was proposed; linear stability analysis using the Routh–Hurwitz criterion indicated a broad parameter region where a stable steady state is attainable, enabling formation of an interpretable analytical signal. The detection limit is associated with monotonic instability, whereas potential oscillatory behavior is expected beyond the analytical working range. Conclusions. A plasticized PVC-based ISE incorporating a triazole-derived Schiff base and ionogenic additives (NaBPh / TOABr) was proposed for potentiometric β-estradiol determination; theoretical analysis supports its electroanalytical feasibility and controllable steady-state operation.
The aim of the work is to establish morphological and anatomical diagnostic features of the underground organs of the Serratula coronata, harvested at the research sites in the Ternopil region in October 2025. Materials and methods. The material for the research was the rhizome and roots of the S. coronata. The morphological and anatomical structure of the studied raw material was studied in accordance with the requirements of the monograph of the State Pharmacopoeia of Ukraine. Fresh and dried raw materials were used. When studying temporary preparations, the Delta Optical Genetic Pro optical device was used and a camera Delta Optical DLT-Cam Pro. Results. According to external signs, the rhizome of Serratula coronata L. is short, woody and thick, from which numerous, thin, cylindrical branched, cord-like, adventitious roots depart. The color of the rhizome from the outside is dark brown, of the adventitious roots is dark brown, on the fracture it is whitish or yellow, the fracture surface is fibrous. The smell is weak and specific. The taste is bitter and astringent. The rhizome has a bundle-free type of structure. The covering tissue is the periderm, which includes the cortex. The cortex is absent in cross section; several rows of brown cells are located, partially torn; the cortex consists of several rows of tangentially elongated parenchyma cells, and near the inner edge narrow secretory ducts form a ring around the endoderm; the endoderm has a narrow Casparian strip; secondary phloem of the parenchyma with bundles of conductive tissue near the cambium; secondary xylem consists mainly of parenchyma, with vessels arranged in narrow radial rows; pith and starch are absent. Inulin is present in all parenchyma cells. Conclusions. A morphological and anatomical study of the rhizome and adventitious roots of Serratula coronata L. was carried out and the main macroscopic and microscopic diagnostic features of underground organs were established.
Aim. The study aimed to identify new pharmacologically active compounds among derivatives of 2-imino-2H-chromene-3-carboxylic acids, specifically through the synthesis of 1-naphthylamides of these acids and evaluation of their effects on cancer cell proliferation. Materials and methods. Organic synthesis was performed, and the structures of the synthesized compounds were confirmed using instrumental analytical techniques. Pharmacological screening was subsequently conducted. Results. N-(1-naphthyl)cyanoacetamide was obtained by reacting 1-naphthylamine with ethyl cyanoacetate under heating. This intermediate was then converted into N-(1 naphthyl)amides of 2-imino-2H-chromene-3-carboxylic acids via Knoevenagel condensation with salicylic aldehydes. The reaction was carried out in 2-propanol with piperidine as a catalyst. The in vitro antiproliferative activity of the synthesized compounds was tested against cell lines of common human tumors: leukemia (6 lines), lung cancer (9), colon cancer (7), renal cancer (8), ovarian cancer (6), prostate cancer (2), breast cancer (8), CNS tumors (6), and melanoma (8). Activity was assessed by comparing the optical density of cell cultures stained with sulforhodamine B before and after exposure to the test compounds dissolved in dimethyl sulfoxide. Conclusions. In vitro testing revealed that 7-hydroxy-2-imino-2H-chromene-3-[N-(1-naphthyl)]carboxamide (4d) exhibited the highest activity, significantly inhibiting the growth of most cultures (GI50 1.5–4.5 μM), with potency equal to or exceeding that of the reference drug. Furthermore, 6-methoxy-2-imino-2H-chromene-3-[N-(1-naphthyl)]carboxamide (4b) showed pronounced selectivity and efficacy against breast cancer cell lines MDA MB 435 (GI50 0.32 μM) and MDA N (GI50 0.46 μM), surpassing the reference drug severalfold. These findings experimentally confirm that the presence of a hydroxyl group at the 7th position of the 2H-chromene ring enhances activity, consistent with literature reports on the ability of related amides to inhibit tyrosine kinase enzymes.
Heterocyclic compounds play a key role in the development of novel biologically active agents, among which pyrrole and 1,2,4-triazole attract particular attention. The combination of these fragments within a single molecule is considered a promising strategy for the design of new drug candidates. The aim of this study was the in silico evaluation of toxicological, pharmacokinetic and pharmacodynamic properties of S-alkylderivatives of 4-methyl-5-(pyrrol-2-yl)-1,2,4-triazole-3-thiol to assess their potential as bioactive substances. Materials and methods. The studied series of S-alkylderivatives of 4-methyl-5-(pyrrol-2-yl)-1,2,4-triazole was designed considering synthetic feasibility. Toxicity predictions were performed using TEST, while physicochemical and pharmacokinetic properties were evaluated via SwissADME. Molecular docking was conducted to assess ligand interactions with enzyme active sites, using MarvinSketch, HyperChem, AutoDock Tools and AutoDock Vina. Results. Toxicity prediction using the TEST software indicated that the LD50 values in rats ranged from 341.55 to 528.74 mg/kg, with a trend toward reduced toxicity upon elongation of the thioalkyl substituent. Conversely, for aquatic organisms, an opposite trend was observed: elongation of the alkyl chain increased lipophilicity and toxicity. Molecular docking demonstrated the ability of the compounds to form stable complexes with the active sites of COX-2, lanosterol 14α-demethylase (CYP51) and ALK kinase. The highest affinities were observed for compound 4 (COX-2), compound 7 (CYP51) and compound 11 (ALK kinase). Interactions included hydrophobic contacts, π-π stacking, π-cation and electrostatic interactions. Pharmacokinetic modeling using SwissADME indicated good oral bioavailability and absorption for most derivatives (2–10), blood-brain barrier permeability, no CYP3A4 inhibition and compliance with drug-likeness criteria. Elongation of the thioalkyl fragment was associated with increased LogP and decreased aqueous solubility, which may limit certain pharmacokinetic parameters. The most balanced profiles were observed for compounds 3–10. Conclusions. The results indicate that S-alkylderivatives of 4-methyl-5-(pyrrol-2-yl)-1,2,4-triazole-3-thiol are promising candidates for further preclinical studies as potential anti-inflammatory, antifungal and anticancer agents.
Rational design of novel biologically active compounds relies on the use of effective structural fragments capable of providing high bioaffinity, favorable pharmacokinetic properties, and an adequate safety profile. Among them, scaffolds based on 1,2,4-triazole and indole occupy a special place; they are widely represented in pharmacologically active molecules due to their ability to participate in diverse types of molecular interactions. Combining 1,2,4-triazole and indole fragments within a single molecule promotes the formation of conjugated systems with potentially multifunctional activity, thereby expanding opportunities for the development of new therapeutic agents. Computer-aided prediction of toxicological and pharmacokinetic properties at early stages of development remains a key strategy for optimizing screening. The use of in silico methods enables timely assessment of safety, the ADME profile and biological potential prior to experimental studies. The aim of the study was an in silico evaluation of ADME parameters and molecular docking results for 3-((indol-3-yl)methyl)-6-methyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine-7-carbohydrazide and its N′-arylidene carbohydrazide derivatives, to substantiate the feasibility of their synthesis and further experimental investigations. Materials and methods. The study was performed using computational methods. Drug-likeness and pharmacokinetic parameters were calculated with the SwissADME online platform. Molecular docking was carried out using AutoDock Vina and Discovery Studio Visualizer, applying the optimal parameters of the docking grid and analysis of interactions between the ligands and active sites of the target proteins. The following targets were selected: lanosterol 14α-demethylase (CYP51, PDB: 5V5Z), cyclooxygenase-2 (COX-2, PDB: 5IKR), peptide deformylase from Staphylococcus aureus (PDF, PDB: 1Q1Y), peptide deformylase from Escherichia coli (PDF, PDB: 1G2A), and anaplastic lymphoma kinase (ALK, PDB: 2XP2). Results. The studied compounds have a high proportion of aromatic fragments and low saturation, accompanied by variable solubility and a generally acceptable drug-likeness profile. Molecular docking revealed target-specific lead compounds. The highest stability of COX-2 complexes was predicted for compounds 4 and 6 (ΔG = -10.2 kcal/mol). Compound 5 demonstrated the strongest binding to lanosterol 14α-demethylase with a binding energy of -11.0 kcal/mol. For peptide deformylase from S. aureus, compound 6 showed the most favorable interaction (ΔG = -8.4 kcal/mol), whereas compounds 7 and 9 were identified as the best binders to E. coli peptide deformylase (ΔG = -7.1 kcal/mol). In the case of ALK, compound 8 exhibited the highest binding affinity (ΔG = -9.0 kcal/mol). Conclusions. The analyzed compounds may be considered as promising scaffolds for further in vitro and in vivo studies, particularly as potential multitarget pharmacological agents. The most relevant candidates for experimental validation are compounds 2, 5–8 and 10, as they combine a favorable pharmacokinetic balance with high predicted binding affinity toward several biological targets.
The endocrine apparatus of the pancreas represents a micro-organ that includes multiple endocrine cell populations that function in close interaction with the microvasculature, extracellular matrix, and immune microenvironment. Within pancreatic islets, oxygen acts not only as an energetic substrate but also as a regulatory signal that modulates transcriptional programs and tissue adaptation through HIF-dependent and HIF-independent mechanisms. Dosed exogenous hypoxia, as a controlled form of intermittent hypoxia, is considered within the concept of hypoxic conditioning and can induce adaptive remodeling, with outcomes critically dependent on the parameters of hypoxic exposure. Investigation of the pancreas under conditions of dosed exogenous hypoxia is therefore promising for delineating the boundary between adaptive reorganization and maladaptive phenotypes and for correlating morphological changes with molecular markers of plasticity and stress responses. Aim. To determine the molecular mechanisms of cellular plasticity and pancreatic tissue remodeling under conditions of dosed exogenous hypoxia through analysis of the expression profiles of key regulatory genes. Materials and methods. Gene expression was analyzed using reverse transcription quantitative polymerase chain reaction (RT-qPCR) with the PARN-405Z RT2 ProfilerTM PCR Array Rat Stem Cell kit (QIAGEN, Germany). The pancreas of experimental animals served as the object of investigation. Results. Dosed exogenous hypoxia is associated with increased expression of genes belonging to three interconnected functional modules: trophic-cytoprotective, cytoskeletal-secretory, and adhesive-matrix. The most expressed transcriptional changes (Igf1 7.82-fold; Cdc42 4.66-fold; Ncam1 3.34-fold; Col1a1 4.23-fold, 2–ΔΔCt) reflect adaptive remodeling, reinforcement of trophic support, optimization of secretory readiness, and reorganization of islet tissue architecture. Moderate upregulation of Krt15 (2.39-fold) and Cdk1 (2.21-fold) corresponds to activation of reparative-plastic programs without signs of excessive proliferation. Conclusions. Overall, the transcriptional profile induced by dosed exogenous hypoxia is consistent with controlled adaptive remodeling of the pancreatic endocrine apparatus in response to microenvironmental changes rather than dominance of injury-driven mechanisms.
The aim. To comprehensively assess the effect of amino acids on lipid profile indicators, atherogenic index, body mass index, and Lee index in rats with experimental diabetes mellitus types 1 (DM1) and 2 (DM2). Materials and methods. DM1 was induced in old male Wistar rats by a single administration of 45 mg/kg streptozotocin. In rats with DM2, insulin resistance was first induced (high-fat mixed feed for 8 weeks), after which 30 mg/kg streptozotocin was administered once. After 6 weeks, animals with DM were divided into 3 subgroups: without amino acid administration, rats with L-arginine and with N-acetyl-L-cysteine. Results. In rats with DM1, there was an increase in total cholesterol (by 50 %), triglycerides (3.3 times) and low-density lipoproteins (1.9 times), which led to a significant increase in the atherogenic index (3.1 times). In rats with DM2, dyslipidemia was more expressed: the atherogenic index exceeded the values of DM1 by 58 %, and the HDL / LDL ratio was disturbed. The administration of L-arginine improved the lipid profile in both groups, significantly reducing the levels of cholesterol, triglycerides and LDL, as well as reducing the atherogenic index. N-acetyl-L-cysteine also had a positive effect on the lipid profile, in particular, it reduced LDL, but its effect was less pronounced. Conclusions. Dyslipidemia in DM1 is characterized by hypertriglyceridemia, hypercholesterolemia with an increase in low-density lipoproteins and a moderate increase in the atherogenic index, accompanied by a decrease in body mass index and the Lee index. While in DM2, more pronounced atherogenic dyslipidemia is observed, which is manifested in a significant decrease in high-density lipoproteins, an increase in low-density lipoproteins with a violation of their ratio against the background of severe hypercholesterolemia, hypertriglyceridemia and an increase in the atherogenic index. The body mass index and the Lee index do not change compared to control values. The introduction of L-arginine significantly improves the lipid profile in both types of diabetes, normalizing the number and ratio of lipoproteins, reducing cholesterol, triglycerides and the atherogenic index, without affecting the body mass index and the Lee index. The effect of N-acetyl-L-cysteine on the lipid profile is positive, but less pronounced compared to L-arginine, causing a decrease in low-density lipoproteins with restoration of the fractional ratio in both types of diabetes, and triglycerides only in rats with type 1 diabetes, but has no significant effect on the atherogenic index, body mass index and Lee index.
Heterocyclic compounds play a key role in the development of new biologically active substances, among which 1,2,4-triazole derivatives attract particular attention. The combination of this heterocyclic core with other heterocyclic pharmacophoric fragments within a single molecule is considered a promising strategy for the design of potential drug candidates. The aim of this study was to evaluate the potential antimicrobial activity of 4-((furan-2-ylmethyl)amino)-3,5-dimethyl-1-(2-aryl-2-oxoethyl)-1,2,4-triazolium bromides using molecular docking to the peptide deformylase (PDF) of Escherichia coli and Staphylococcus aureus. Materials and methods. The three-dimensional structures of the ligands were modeled using ChemSketch software, while the crystallographic structures of the peptide deformylase (PDF) enzyme were obtained from the Protein Data Bank: the Escherichia coli isoform (EcPDF, PDB ID: 1BSK) and the Staphylococcus aureus isoform (SaPDF, PDB ID: 1LQW) were used. Molecular docking was performed using AutoDock Vina, and the types of intermolecular interactions were analyzed with Discovery Studio Visualizer. The minimum binding energy (Emin), reflecting the stability of the “ligand – enzyme” complex, was used as an indicator of binding efficiency. Results. Nitro-substituted compounds exhibited the highest affinity towards the active sites of both enzymes. In particular, the ortho-nitro derivative showed Emin values of -7.5 kcal/mol for the E. coli PDF complex and -7.9 kcal/mol for the S. aureus PDF complex, surpassing the activity of the standard inhibitor actinonin (Emin = -6.7 kcal/mol). Hydroxy-substituted derivatives demonstrated moderate activity, whereas the introduction of a methoxy group into the aryl fragment decreased the affinity of the ligands toward the enzyme. Conclusions. A clear structure – activity relationship (SAR) was established, indicating that antimicrobial activity increases in the order of aryl substituents: -OCH3 < -OH < -NO2. The ortho-nitro derivative proved to be the most promising, forming multiple hydrogen bonds, π-cation and hydrophobic interactions with amino acid residues in the catalytic site of PDF. The obtained results can be used for the further design and optimization of novel peptide deformylase inhibitors of bacterial origin.
The aim of the article is to predict the potential pharmacological activity of N-aryl-tetrahydro-5H-[1,2,4]triazolo-[4,3-a]azepin-3-ylmethyl)-amines and to establish a correlation relationship between the probability of biological activity and quantum chemical parameters of molecules. Materials and methods. The calculation of quantum chemical parameters of molecules was performed using the ChemOffice software. Prediction of bioavailability and pharmacokinetic parameters was performed using the SwissADME online resource. Prediction of probable target proteins was performed using the online resource SuperPred. Molecular docking was performed using Webina 1.0.5, visualization and analysis of interactions were performed using Discovery Studio Visualizer. Microsoft Excel was used to perform correlation and regression analyses on the coordinates “binding affinity – quantum chemical descriptors.” Results. The molecules of the studied triazoloazepine derivatives have electrophilic properties, as indicated by the energy values of the lower vacant molecular orbital. They contain several adsorption reaction centers, in particular, positively charged amine nitrogen atom and nitrogen atom common to the triazole and azepine cycles, as well as negatively charged nitrogen atoms of the triazole cycle. According to calculations, high bioavailability and low risks of hepatotoxicity and neurotoxicity are expected, meeting the requirements for potential drugs. An assessment of the compliance of triazoloazepine derivative molecules with the physicochemical parameters of bioavailability was carried out using radar diagrams. Correlation relationships were found between the probability of binding to Cathepsin D and Glutathione S-transferase Pi proteins and the quantum chemical parameters of the molecules. Good affinity was established for binding to proteins of the Carbonic anhydrase (VII, XII), Monoamine oxidase A and B, and Progesterone receptor. Binding occurs mainly with the participation of the electron density of cyclic fragments of molecules in the formation of π-alkyl, π-cation, π-π, π-σ, and stacking bonds. The interaction between triazoloazepine derivatives and potential target proteins occurs mainly with the participation of the electron density of cyclic fragments of molecules. Conclusions. N-aryl-N-(6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-3-ylmethyl)-amines derivatives were found to have a high probability of binding to several potential target proteins. The formation of enzyme-ligand complexes may occur mainly with the participation of the electron density of cyclic fragments of molecules. The results obtained are important for further study of new triazoloazepine derivatives as perspective drug substances.
The aerial parts of Valeriana collina and Valeriana stolonifera are considered a promising source of bioactive compounds with antimicrobial and hepatoprotective properties; however, their pharmacological characteristics have not been sufficiently studied. The aim of the work. To comprehensively evaluate the antimicrobial / antifungal potential, acute toxicity, and hepatoprotective activity of thick extracts from the herbs of V. collina and V. stolonifera. Materials and methods. Antimicrobial activity was determined by the agar diffusion method (well method). Acute toxicity was evaluated in Wistar rats according to OECD guidelines. Hepatoprotective activity was studied in a paracetamol-induced hepatitis model by measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels; silymarin was used as the reference drug. Results. Both extracts exhibited a broad spectrum of antimicrobial activity; V. stolonifera was more effective against P. aeruginosa (p = 0.0113), while V. collina showed higher activity against C. albicans (p = 0.0080). Both samples were classified as low-toxicity (GHS Category 5). In the hepatitis model, V. stolonifera significantly reduced ALT, AST, and ALP levels, being not inferior – and in the case of ALP, superior – to silymarin. Conclusions. Both thick extracts of V. collina and V. stolonifera demonstrated pronounced antimicrobial activity against gram-positive and gram-negative bacteria as well as C. albicans. V. stolonifera was more effective against P. aeruginosa, whereas V. collina showed higher activity against C. albicans. These differences may be associated with variations in the ratios of biologically active compounds within the extracts, supporting the need for further chemical and pharmacological studies to elucidate mechanisms of action. A 20 % aqueous solution of the thick extract of V. collina administered intragastrically can be classified as toxicity class 5, with an LD50 ranging from 2000–5000 mg/kg. The solution of the thick extract of V. stolonifera caused no mortality in rats, classifying it as a substance with low acute toxicity (GHS Category 5, LD50 ≥5000 mg/kg). Further testing of the studied samples is not recommended unless specifically required for regulatory purposes. The studied valerian extracts, especially V. stolonifera, exhibited an expressed hepatoprotective effect in a paracetamol-induced hepatitis model in rats. The paracetamol-induced hepatitis led to marked biochemical and morphological signs of liver damage in rats. The V. stolonifera extract demonstrated a clear hepatoprotective effect, evidenced by reduced ALT, AST, and ALP levels and a decrease in the necrotic area of the liver. The effectiveness of the V. stolonifera extract exceeded that of the reference drug, silymarin.
