Russian Journal of Bioorganic Chemistry最新文献

Objective: The study aims to develop an efficient method for the sulfation of betulin 3-propionate using a sulfamic acid–urea mixture in N,N-dimethylformamide medium. The goal is to synthesize various derivatives of betulin 3-propionate sulfates, avoiding the use of aggressive sulfating reagents such as sulfur dioxide and sulfuric acid. Methods: Betulin 3-propionate was sulfated with a sulfamic acid–urea mixture in N,N-dimethylformamide. The reaction was conducted at temperatures of 45–50°C for 3 h. The sulfated products (ammonium salt, acidic form, potassium salt, and sodium salt) were isolated by diluting the reaction mixture with water and extracting with butanol. The yield of the sulfates was determined, and the compositions of the products were confirmed by elemental analysis. The structure of the sulfated products was analyzed using FT-IR and ¹³C NMR spectroscopy. Results and Discussion: The sulfation process successfully produced 28-sulfates of betulin 3-propionate in high yields (91, 89, 89, and 90% for ammonium salt, acidic form, potassium salt, and sodium salt, respectively). The composition of the obtained sulfates was confirmed by elemental analysis, with sulfur content ranging from 5.03 to 5.32%. The FT-IR spectra showed characteristic absorption bands for the sulfate group at 830–833 cm^–1 (C–O–S) and 1225–1227 cm^–1 (O=S=O). The ¹³C NMR analysis confirmed the complete substitution of the hydroxyl group at C₂₈ with the sulfate group, as evidenced by a chemical shift from 60.6 ppm (in betulin 3-propionate) to 66.0 ppm (in the sodium salt of the sulfate). Conclusions: The sulfation of betulin 3-propionate using a sulfamic acid–urea mixture in N,N-dimethylformamide is an efficient method that avoids the use of aggressive reagents. The synthesis of betulin 3-propionate 28-sulfate derivatives was successful, and the structure of the sulfates was confirmed by FT-IR and ¹³C NMR spectroscopy. This method offers a promising approach for the modification of betulin derivatives for potential bioactive applications.

The review considers changes in ideas about the biosynthesis, structure, and functions of lignin in plants, starting from early references to the present day. Alternative viewpoints on the process of lignin biosynthesis, lignin spatial and supramolecular structure, and the nature of lignin-carbohydrate bonds were presented. A special place in the review belongs to the results of studies of lignin with the aim of reducing its content and changing the composition of the monomer units using genetic engineering methods. Comparison of the structures of the lignins isolated from transgenic and mutant trees and herbaceous plants showed that lignin biosynthesis is plastic and may involve, alongside canonical monolignols (coniferyl, sinapyl, and coumaryl alcohols), other phenolic compounds. Studies of so-called “stress lignins” demonstrated an important role played by lignin in plant protection against adverse environmental influences: mechanical damage, drought, low temperatures, pathogens, etc. The results of studies on gene modification of lignin allowed outlining a strategy of directed modification of the lignin biosynthesis process with the aim to obtain designer lignins, i.e., lignins with desired properties. This group includes so-called zip-lignins; they are characterized by the presence of ester linkages between the phenylpropane units. It is noted that, when conducting research into gene engineering of lignin, it is necessary to find a compromise between improving the processability of plant raw materials through lignin modification and the viability of transgenic plants.

Objective: To analyze the content of biologically active substances (BAS) and antioxidant properties of four Agastache species (A. rugosa, A. foeniculum, A. urticifolia, A. mexicana) across different phenological phases. Methods: Content of flavonols, catechins, tannins, pectins, protopectins, saponins, and carotenoids in leaves, inflorescences, and stems was determined using spectrophotometric and gravimetric methods. Total antioxidant content (TAC) was measured by amperometry. Results and Discussion: Leaves and inflorescences were the main BAS accumulators. Tannin content in leaves was twice that in inflorescences, while carotenoids were an order of magnitude higher in leaves. Maximum TAC (>2 mg/g) was found in leaves during mass flowering. Catechins and tannins showed the strongest correlation with antioxidant activity (r = 0.69 and 0.63, respectively). Conclusions: The flowering period is the optimal time for harvesting Agastache raw materials, as plants are richest in BAS and exhibit the highest antioxidant activity. The leaves are the most valuable plant part.

Objective: The aim of this study was to explore the potential of humic substances (HS) as non-β-lactam inhibitors for β-lactamase, using molecular modeling to understand the interaction between humic-like molecules and β-lactamase, particularly TEM-1. Methods: Molecular dereplication of humic-like inhibitors was performed by comparing their molecular formulas, derived from high-resolution mass spectrometry, to known compounds in the ChEMBL database. The interaction of selected humic-like molecules with β-lactamase was studied using docking and molecular dynamics simulations with Chimera v.1.15 and Amber14 software. Results and Discussion: From dereplication, 156 unique structures were identified as β-lactamase inhibitors. Three molecules were selected for molecular modeling based on their lipophilicity and similarity to HS. Docking simulations revealed that the humic-like molecules interacted with the enzyme through non-competitive inhibition, binding to an allosteric site, and also showed aggregation behavior on the protein surface. Molecular dynamics simulations suggested that the aggregation of humic-like ligands could block the active site of β-lactamase, enhancing the synergistic effect on sulbactam. Conclusions: This study demonstrates that humic-like molecules can interact with β-lactamase through non-competitive inhibition and aggregation, potentially improving the efficacy of existing β-lactamase inhibitors. The dereplication method proved valuable for identifying active components within humic substances, offering a novel approach to discovering non-β-lactam inhibitors.

Objective: An important aspect of the processing and pre-processing of cellulose raw materials (including bran) is to obtain a high content of reducing agents in the final product. Experimentally selected process parameters and optimization of pre-processing conditions of plant raw materials, tailored to increase the amount of biologically valuable substances, will reduce the cost of the final product. In this work, the bioconversion of wheat bran polymers was carried out with hydrolytic enzyme preparations (ЕР). Methods: The degree of biotransformation of plant polymers was evaluated using crushed wheat bran with enzyme preparations and their complexes by chemical analysis and HPLC. Results and Discussion: The feedstock (wheat bran) was characterized by a low content of lignin (7.55%) and high pentosan content (17.9%). The largest amount of reducing substances in hydrolysates was determined for ЕР Amylolux ATS (0.23 g/g of raw materials), and for its complexes Amylolux ATS and Cellolux A (0.29 g/g of raw materials). The inclusion of proteolytic enzymes in the ЕР complex increases the amount of amine nitrogen (39.5 mg/g), while reducing kinematic viscosity. A greater amount of mannose (56.0 mg/g of bran), but less pentose (4.1 mg/g of bran) of hydrolysates of enzymatically processed wheat bran was determined in comparison with chemical treatment. Conclusions: Optimal parameters of enzymatic pretreatment of wheat bran for their conversion into biologically valuable carbohydrates have been determined, which is a promising direction of research and their practical use in the production of mannose, biofuels, chemicals and food additives.

Objective: The study aims to investigate the solid-state modification of chitosan (Chs) by sorbic acid (SA) through a mechanochemical reaction using a twin-screw extruder under pressure and shear deformation. The goal is to prepare chitosan derivatives with enhanced antifungal properties, particularly against A. niger, to improve their potential applications in food preservation and other industrial fields. Methods: The reaction was carried out in a twin-screw extruder at 80°C, using varying molar ratios of chitosan to sorbic acid (1 : 0.5, 1 : 1, 1 : 1.5). The products were characterized using FT-IR, elemental analysis, thermal analysis (DSC and TGA), dynamic light scattering, and mechanical testing. The antifungal activity of the modified chitosan derivatives was evaluated against A. niger. Results and Discussion: The study found that the degree of substitution (DS) of chitosan derivatives ranged from 0.08 to 0.33, depending on the molar ratio of chitosan to sorbic acid. The FT-IR spectra revealed that the reaction involved both ionic interactions and covalent amide bond formation. The solubility of the derivatives in 2% acetic acid decreased with higher DS values, indicating successful modification. The modified chitosan derivatives exhibited increased antifungal activity against A. niger, with the most effective derivative showing a DS of 0.14. The mechanical properties of films made from the derivatives showed a decrease in elongation at break, suggesting changes in polymer structure due to the acylation process. Thermal stability was also affected, with the insoluble derivatives showing improved thermal stability compared to the unmodified chitosan. Conclusions: The solvent-free mechanochemical acylation of chitosan with sorbic acid in a twin-screw extruder effectively produces chitosan derivatives with enhanced antifungal activity, making them suitable for applications in food preservation and other fields requiring antimicrobial properties. The approach provides a safe, environmentally friendly method for modifying chitosan, expanding its potential uses in various industries such as food, pharmaceuticals, and cosmetics.

Objective: Nucleoside derivatives are widely used for drug development. We previously obtained N⁴-alkyl derivatives of 2′-deoxycytidine and cytidine, which showed significant inhibitory activity against Gram-positive bacteria, but the exact mechanism of their action remains unexplained at present. One of the methods for elucidating the mechanisms of action of biologically active molecules and, consequently, for increasing their therapeutic effectiveness is identifying the subcellular localization of low-molecular-weight compounds. Methods: In this study, new derivatives of N⁴-dodecyl-5-methyl-2′-deoxycytidine containing terminal amino groups at the end of an alkyl linker have been synthesized. It is shown that they are convenient synthons for the subsequent introduction of dansyl fluorophore groups. Results and Discussion: One of the N⁴-ω-dansylaminoalkyl derivatives has shown moderate antibacterial activity against the Mycobacterium smegmatis strain. This derivative can be used to study the subcellular localization. Conclusions: The synthesized derivatives have potential for further research, particularly in studying their subcellular localization.

Coumarins, a class of benzopyran-derived compounds, have emerged as versatile bioorganic building blocks with significant roles in drug design, biocatalysis, and sensing applications. These naturally occurring and synthetically derived molecules exhibit a wide range of biological activities, including antimicrobial, anti-inflammatory, anticancer, and anticoagulant properties. Due to the diversity of hydroxyl, methoxy, and prenyl substitutions, coumarins can adopt various structures, enabling functionalization for a broad spectrum of biomedical and industrial uses. In the field of drug discovery, coumarins have been extensively studied as enzyme inhibitors, fluorescence probes, and molecular scaffolds for novel therapeutics. Their ability to form both covalent and non-covalent interactions with biological targets makes them promising candidates for pharmaceutical development. Due to their unique photophysical properties, coumarins can also serve as molecular sensors for detecting metal ions, reactive oxygen species, and biomolecules in living systems. Biocatalysis has also benefited from the incorporation of coumarins, as they act as substrates and modulators in enzyme-mediated transformations. Enzymatic pathways for coumarin biosynthesis and functionalization have been explored to improve their accessibility and biocompatibility. Recent advances in biotechnological approaches, such as metabolic engineering and microbial synthesis, have further facilitated the production of complex coumarin derivatives with tailored bioactivities. Furthermore, coumarins play a key role in the development of optical and electrochemical sensors due to their tunable fluorescence and electron transfer properties. They have been employed in environmental monitoring, disease diagnostics, and chemical safety assessments, demonstrating their broad applicability beyond medicinal chemistry. Despite their promising potential, challenges such as bioavailability, toxicity, and regulatory constraints must be addressed to optimize their therapeutic and industrial utility. This review comprehensively examines the chemical, biological, and functional aspects of coumarins in bioorganic chemistry, highlighting their significance in modern scientific and technological advancements. By integrating recent findings and emerging trends, this article aims to provide insights into the future directions and innovations in coumarin-based research.