Roza Battalovna Seidakhmetova

Background/Objectives: This study compared five ultrasound-assisted extracts of Prunella vulgaris L. prepared with water or aqueous ethanol (30%, 50%, 70%, and 96%) and evaluated their phytochemical composition and preliminary antimicrobial, anti-inflammatory, brine-shrimp lethality, and antioxidant properties. Methods: Gallic acid and rosmarinic acid were quantified in all five extracts by a validated HPLC-UV method, with LC-ESI-MS used to support compound identification. Antimicrobial activity was evaluated by broth serial dilution and minimum inhibitory concentration (MIC) determination. Anti-inflammatory activity was assessed in a carrageenan-induced rat paw edema model. General toxicity screening was performed using the Artemia salina lethality assay. Antioxidant activity was evaluated by a ferricyanide reducing-power assay and the DPPH radical-scavenging assay. Results: Rosmarinic acid was detected in all extracts and was most abundant in PV70 (7.6%). PV70 showed MIC values of 12.5 μg/mL against Staphylococcus aureus and Bacillus subtilis. In the carrageenan model, PV70 produced 76.8% inhibition of paw-weight gain at 25 mg/kg, whereas diclofenac produced 66.6% inhibition at 10 mg/kg; this numerical comparison was descriptive and was not interpreted as evidence of superiority. The tested extracts caused low mortality of Artemia salina under the experimental conditions. Conclusions: The findings identify PV70 as a chemically distinct extract with notable activity in the screening models used. Because the extracts are multicomponent mixtures and mechanistic biomarkers were not measured, the observed biological effects cannot be attributed to rosmarinic acid alone. Further work is required to confirm mechanisms, safety, standardization, and efficacy.

This study investigates the N-phosphorylation of key mono- and diaminoheterocycles within the thiazole and thiadiazole series using dimethyl chlorophosphate (P(V)) and 1-tert-butoxy-N,N,N',N'-tetraethylphosphanediamine (P(III)) reagents. Eight novel derivatives were successfully synthesized and isolated. Reaction conditions were optimized, employing triethylamine in acetonitrile at 80 °C for P(V) agents, and ethyl acetate at 80 °C via diethylamine elimination for P(III) agents. Diamino substrates underwent efficient, symmetric bis-phosphorylation at both exocyclic amino positions. Due to the electron-withdrawing effect of the second endocyclic nitrogen in the thiadiazole core, its amino groups showed lower nucleophilicity, resulting in lower yields (31–41%) compared to thiazole counterparts (65–83%). Structural frameworks were confirmed by 31P NMR spectroscopy, appearing at δ 5.85–5.92 ppm for phosphoramidates and δ 124.66–128.48 ppm for phosphoramidites. In vitro screening demonstrated a strong, dose-dependent antimicrobial profile, with Gram-negative strains displaying enhanced susceptibility. Trivalent phosphorus derivative emerged as the most potent broad-spectrum candidate. Against P. aeruginosa, 1-tert-butoxy-N,N-diethyl-N'-(1,3,4-thiadiazol-2-yl)phosphanediamine exhibited a 27–33 mm inhibition zone, outperforming streptomycin (MIC = 6.25, MBC = 12.5 µg/ mL). Against T. viride, it outclassed clotrimazole with a 30–39 mm zone (MIC = 12.5, MFC = 25 µg/mL). The results obtained open up broad prospects for the development of new, highly effective antibacterial and antifungal agents based on phosphorylated heterocycles.

Liver-targeted drug delivery offers opportunities to increase therapeutic exposure at sites of hepatic disease while limiting systemic toxicity; however, successful targeting requires more than preferential accumulation of a carrier within the liver. This narrative review critically summarizes recent advances in synthetic, biological, and biomimetic delivery platforms, including lipid, polymeric, inorganic, and protein-based nanoparticles, nucleic acid nanocarriers, extracellular vesicles, plant-derived nanovesicles, cell-mediated systems, and cell membrane-coated nanoparticles. A literature search was conducted using PubMed, Web of Science, and Embase, with emphasis on studies published during the last decade and updated through 24 August 2026. Particular attention is given to the biological determinants of hepatic biodistribution, including sinusoidal architecture, physicochemical carrier properties, protein corona formation, receptor–ligand interactions, and disease-associated alterations in the hepatic microenvironment. The review distinguishes organ-level hepatic accumulation from cell-specific uptake and productive intracellular delivery and discusses strategies directed toward hepatocytes, hepatic stellate cells, Kupffer cells and other macrophages, liver sinusoidal endothelial cells, neutrophils, and additional immune-cell populations. Major delivery platforms are critically compared with respect to the evidence supporting targeting specificity, cargo compatibility, administration route, reported safety and immunogenicity, manufacturability, analytical characterization, and translational maturity. Particular consideration is given to extracellular vesicle- and plant-derived nanovesicle-based approaches, for which biological activity, biodistribution, standardization, and scalability remain important areas of investigation. Overall, current research in liver-targeted delivery is increasingly focused on moving beyond nonspecific organ accumulation toward disease-adapted, cell-specific, and intracellularly productive delivery, although substantial biological, manufacturing, and regulatory challenges remain before many emerging approaches can achieve routine clinical translation.

The continuous search for new chemical structures more active and less toxic than those currently in practice is justified on the basis of the use of proven pharmacophoric building blocks (benzimidazole heterocycle, sulfonyl group and amidoxime framework in our case). The aim of the work was to synthesize new O-alkylsulfonyl-β-(benzimidazol-1-yl)propioamidoximes and to test them for in vitro biological activities to identify potentially effective agents. Novel O-alkylsulfonylamidoximes were synthesized in hydrochloride and base forms by the reaction of β-(benzimidazol-1-yl)propioamidoxime with alkylsulfonyl chlorides AlkSO₂Cl (Alk = CH₃, n-C₃H₇, i-C₃H₇, n-C₄H₉) in a mixture of water:acetone in hydrochloride and base forms. Hydrochlorides and bases of the O-alkylsulfonyl-β-(benzimidazol-1-yl)propioamidoximes were obtained in moderate to high yields. The structures of the synthesized compounds were established by physicochemical and spectral (elemental analysis, FT-IR, NMR and X-ray diffraction) methods. The obtained derivatives were tested for antimicrobial, antifungal and antidiabetic activity. Biological screening found effective samples of amidoximes with antimicrobial and antifungal activities that were near or exceeded the activity of the reference drugs gentamicin and nystatin; in addition, two samples with antidiabetic activity higher than acarbose were found. The results of the present study open new possibilities for the novel β-aminopropioamidoxime class as active antimicrobial and antifungal agents, as well as antidiabetic ones.

The continuous search for new chemical structures more active, less toxic than those currently in practice is justified on the basis of the use of proven pharmacophoric building blocks (benzimidazole heterocycle, sulfonyl group and amidoxime framework in our case). The aim of the work was to synthesize new O-alkylsulfonyl- b -(benzimidazol-1-yl)propioamidoximes and to test them for in vitro biological activities to identify potential effective agents. Novel O-alkylsulfonylamidoximes were synthesized by the reaction of b -(benzimidazol-1-yl)propioamidoxime with alkylsulfonyl chlorides AlkSO₂Cl (Alk = CH₃, n-C₃H₇, i-C₃H₇, n-С₄H₉) in a mixture of water: acetone in hydrochloride and base forms. Obtained derivatives were tested for antimicrobial, antifungal and antidiabetic activity. Hydrochlorides and bases of the O-alkylsulfonyl- b -(benzimidazol-1-yl)propioamidoximes were obtained in moderate to high yields. The structures of the synthesized compounds were established by physicochemical and spectral (FT-IR, NMR and X-ray diffraction) methods. Biological screening found effective samples of amidoximes with antimicrobial and antifungal activities which were near or exceeded the activity of the reference drugs gentamicin and nystatin; in addition, two samples with antidiabetic activity higher than acarbose were found. Results of the present study open new possibilities for the novel b -aminopropioamidoxime class as active antimicrobial and antifungal agents, as well as antidiabetics ones.

The year 2024 marked the 80th anniversary of Woodward’s total synthesis of quinine. Quinine is a natural alkaloid from the bark of the cinchona tree that has been used for years as an antimalarial drug. The antibacterial effect of quinine salts has also been regarded. With this in mind, a series of original 9-deoxycinchone alkaloid derivatives bearing a dialkylamino- or heterocyclic moiety at the 4 position of the 9-(((4-X-but-2-ynyloxy)methyl)-1,2,3-triazolyl)-substituent was synthesized. The copper-catalyzed three-component A³-coupling reaction of 9-(((4-prop-2-ynyloxy)methyl)-1,2,3-triazolyl)- substituted cinchona alkaloid derivatives with secondary amines and formaldehyde was the main route of synthesis. The present study attempted to examine the antibacterial properties of 9-substituted 9-desoxyquinine-derived compounds and their antibacterial activity against pathogenic bacterial strains, e.g., Staphylococcus aureus, Bacillus subtillis, Bacillus cereus, and Escherichia coli. The difference in the antibacterial activity profile of diastereoisomeric 9-(((4-X-but-2-ynyloxy)methyl)-1,2,3-triazolyl)-substituted derivatives of cinchona alkaloids indicated the importance of the nature of nitrogen substituents in the molecules. In a concentration-dependent pattern, (9R)- and (9S)- (((4-asocan-1yl)-but-2-ynyl-oxy)methyl)-1,2,3-triazolyl)-substituted compounds demonstrated considerable biofilm-inhibitory efficacy against the S. aureus bacterial strain. A detailed study of the molecular interactions with the targeted protein MurB was performed using docking simulations, and the obtained results are quite promising.

This study presents the results of a study of the synthesis and properties of 2-hydroxy-β-cyclodextrin functionalized by silver nanoparticles and its loading with a bioactive component. As a reducing agent and stabilizer, 2-Hydroxy-β-cyclodextrin (2gβCD) was used in the production of silver nanoparticles. The use of 2gβCD-AgNPs in loading molecules of the plant alkaloid lupinine (Lup) and its acetyl derivative (Lac) with bactericidal properties were studied. The formation of Lup-2gβCD-AgNPs and Lac-2gβCD-AgNPs was confirmed by UV spectroscopy and X-ray diffraction spectroscopy (XRD). Transmission electron microscopy (TEM) showed that the synthesized AgNPs had a spherical shape. ¹H-, ¹³C-NMR nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy (FT-IR) confirmed the reduction and encapsulation of AgNPs by 2gβCD. Thermographic data show that the obtained Lup and its derivative inclusion complexes reduced energy barriers. This makes them promising components for thermosensitive functional materials. Encapsulated complexes of Lup and its acetate inclusion with silver nanoparticles demonstrated significantly (p < 0.05) higher antibacterial, cytotoxic, and moderately pronounced analgesic activity.

A synthetic methodology of the CuAAC “click” approach was exploited for the construction of 1,2-azolyltriazole quinine derivatives by the reaction of O-propargylquinine with azidomethyl-1,2-azoles in methanol. Quinine–piperidine and quinine–anabasine conjugates were obtained using a chloroacetate linker by reacting quinine chloroacetate with piperidine or anabasine in a diethyl ether medium. Cinchophene ester was obtained by the acylation of quinine with cinchophen acid chloride in methylene chloride. The antibacterial, fungicidal, analgesic and cytotoxic properties of the obtained compounds were examined.

Replenishing the range of natural and synthetic medicinal substances with different anti-inflammatory activity is an urgent task of modern pharmaceuticals. Studying the anti-inflammatory activity of chemical compounds through bioscreening and in vitro and in vivo studies is a lengthy and labor-intensive procedure. This paper presents the data on the antyinflammatory activity of nitrogenous heterocyclic compounds on a model of acute exudative reaction (peritonitis) and comparison of the obtained data with the results of ab initio quantum chemical calculations using the density functional theory method. Among the 16 studied compounds, 7 representatives were identified with the highest potential antyinflammatory action.

Exosomes are small extracellular vesicles and are crucial in intercellular communication. Interestingly, tumor-derived exosomes carry oncogenic molecules, such as proteins and microRNAs, which can reprogram recipient cells, promote angiogenesis, and stimulate cancer pre-metastatic niche, supporting cancer growth and metastasis. On the other hand, their biocompatibility, stability, and ability to cross biological barriers make them attractive candidates for drug delivery. Recent advances have shown the potential for exosomes to be used in early disease detection and in targeted drug therapy by delivering therapeutic agents specifically to tumor sites. Despite the promising applications, a number of challenges remain, including exosome isolation and characterization, as well as their inherent heterogeneity. Thus, the current review aims to describe the roles of exosomes in health and disease, and discuss the challenges that hinder their development into becoming useful medical tools.