Russian Journal of Bioorganic Chemistry最新文献

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.

Objective: This study focuses on the design, synthesis, characterization, and biological evaluation (in vitro and in silico) of novel [1,2,3]triazolo[1',5':1,5]pyrrolo[3,4-d]pyrimidines (Va–Vo) synthesized via a one-pot method. The compounds were evaluated for their anticancer activity and EGFR inhibitory effects. Methods: The synthesis of fused 1,2,3-triazoles was performed under microwave conditions using PEG-400 as the solvent. All synthesized compounds were assessed for their anticancer activity against MCF-7 and A-549 cancer cell lines. The most potent compounds were further analyzed using an EGFR enzymatic assay and in silico molecular docking studies. Results and Discussion: ESI-MS, ¹H, and ¹³C NMR spectroscopy confirmed the identity of the new derivatives. Compounds (Vk–Vm) exhibited potent activity against MCF-7 cells, with IC₅₀ values of 6.41 ± 0.33, 4.25 ± 0.29, and 5.65 ± 0.31 μM, respectively, compared to the standard 5-FU. Further evaluation of EGFR inhibitory activity showed that compound Vk displayed significant activity. All potent compounds exhibited higher binding energies compared to the standard erlotinib. Conclusions: A series of fused [1,2,3]triazolo[1',5':1,5]pyrrolo[3,4-d]pyrimidines were successfully synthesized and evaluated for in vitro anticancer activity. Some compounds demonstrated notable effectiveness against the MCF-7 cell line. Moreover, the potent compounds exhibited limited toxicity against normal HEK293 cells. All active compounds showed significant binding energies, ranging from –7.76 to –8.65 kcal/mol, compared to the standard erlotinib (–7.69 kcal/mol). Modifications to the potent compound Vk could lead to a promising therapeutic candidate for cancer treatment.

This review discusses the significance of 1,3,4-oxadiazole (OXD) derivatives in medicinal chemistry, focusing on their diverse biological activities and the importance of eco-friendly production methods. The primary objective is to explore green synthetic routes that minimize environmental impact while preserving the pharmacological potential of OXD derivatives. Traditional methods, which typically involve acid hydrazides and dehydrating agents like phosphorus oxychloride, often yield low amounts of product and generate hazardous byproducts, and are also addressed. In contrast, green chemistry techniques, such as solvent-free processes, microwave-assisted synthesis, and the use of non-toxic catalysts, have been shown to improve reaction efficiency, reduce energy consumption, and produce higher yields with fewer environmental risks. The review also emphasizes the structural flexibility of the 1,3,4-oxadiazole core moiety and its ability to be tailored into various derivatives with promising biological activities, including antibacterial, antitubercular, antifungal, anticancer, and antioxidant properties. Green synthetic approaches not only enhance the yield and purity of OXD derivatives but also improve their biological efficacy against cancers and drug-resistant bacteria. Future considerations are discussed, emphasizing the dual benefits of these approaches in supporting environmentally sustainable practices and enhancing the pharmacological profiles of OXD derivatives, which offer a promising strategy for the development of novel therapeutic agents in the pharmaceutical industry.

Objective: Nanocarriers are promising for theranostics, enabling the combination of diagnostics and therapy. The objective of this work was to develop an amphiphilic derivative of the BODIPY-FL fluorescent dye, encapsulate it in cationic liposomes made from lipopeptides, and evaluate the potential of these liposomes as a drug delivery system for anticancer therapy. Methods: An amphiphilic derivative of the BODIPY-FL fluorescent dye was developed and encapsulated into cationic liposomes made from lipopeptides. The liposomes were loaded with the lipophilic anticancer drug sunitinib. Their physicochemical properties, accumulation, localization, and cytotoxicity in human osteosarcoma (HOS) cells were analyzed. Results and Discussion: The fluorescent liposomes successfully penetrated the cells after 15 min of incubation. The cytotoxicity studies revealed that the liposomes induced cell death after 48 h, with an IC₅₀ value of 106.0 ± 10.2 μM. These results suggest that the BODIPY-FL/L-carnitine liposomes hold promise for both diagnostic and therapeutic applications, offering a potential platform for theranostic drug delivery systems. Conclusions: The developed fluorescent liposomes encapsulating sunitinib show promising potential as a novel anticancer drug delivery system, with applications in theranostics for cancer treatment.

Objective: Currently, various drugs have been developed and are being used in practice for the treatment of HIV infection, however, the emergence of multidrug resistance to the drugs used is still a serious problem in anti-HIV therapy. Limitations in the use of existing nucleoside reverse transcriptase inhibitors (NRTIs) have led to the development of strategies for creating prodrugs based on them. The development of prodrugs of antiviral nucleosides with isosteric derivatives of natural lipids makes it possible to increase the bioavailability of these drugs and modulate their efficiency. Methods: In this work, new lipophilic prodrugs of 3′-azido-3′-deoxythymidine (AZT), 2′,3′-dideoxy-3′-thiacytidine (3TC) based on 1,3-(dipalmitoylamino)propan-2-ol were synthesized using the H-phosphonate method. Phosphoramidate derivatives with various esters of L-α-alanine have also been obtained. Results and Discussion: The anti-HIV activity of the synthesized compounds against various HIV strains (HIV-1 MVP-899; HIV-1 RF) and cytotoxicity in relation to MT-4 cells were studied.The H-phosphonatediester and phosphodiester conjugates showed anti-HIV activity inferior to the parent nucleosides, and their advantages include low cytotoxicity (CC₅₀ >100 µM). The phosphodiester conjugate 3TC was inactive in this virus cell system. The antiviral activity of phosphoamidates with L-α-alanine esters decreased in the range (^tBu) >Me > (ⁱPr) > Et. Thus, compounds with methyl, ethyl and isopropyl ether residues showed a similar level of anti-HIV activity (IC₅₀ = 4.60­–12.55 µM), the derivative containing the residue of tert-butyl ether of L-α-alanine (IC₅₀ = 0.46 µM) showed the greatest activity. These compounds showed cytotoxicity similar to AZT (CC₅₀ >50 µM). Conclusions: The new lipophilic derivatives of AZT and 3TC synthesized in the work have low toxicity and exhibit antiviral activity against various clinical isolates of HIV-1. Although they are inferior in effectiveness to the parent anti-HIV nucleosides in cellular models, their cytotoxicity is lower, the advantages of such conjugates include the possibility of increasing the bioavailability of drugs due to enterocyte-mediated lymphatic transport, potential intracellular release of nucleoside monophosphate, which additionally bypasses the limiting stage of primary phosphorylation of nucleosides. Therefore, the design of such prodrugs can serve as the basis for the search for drugs with high efficacy.

Objective: This study evaluated a method for assessing the immunogenicity of synthetic peptides as a potential clinical diagnostic for cellular immune responses to influenza virus. Two 9-mer peptides corresponding to epitopes from the 2023-2024 Northern Hemisphere vaccine strains were used: a 432–440 aa fragment of influenza A hemagglutinin (Phe–Leu–Asp–Ile–Trp–Thr–Tyr–Asn–Ala) and a 454–462 aa fragment of influenza B neuraminidase (Leu–Leu–Trp–Asp–Thr–Val–Thr–Gly–Val). Methods: The peptides were synthesized using classical methods of peptide chemisty, employing carbodiimide condensation with activated amino acid esters. Fifty five volunteers (aged 20–26) too part in the clinical study. Gamma interferon (IFN-γ) production was measured by the ELISA assay. Results and Discussion: No statistically significant differences in IFN-γ levels were observed across any pairwise comparisons. Conclusions: The diagnostic method requires further optimization before it can be reliably used for clinical assessment of cellular immune response to influenza A virus.

Azepine is a seven-membered, nitrogen-containing heterocyclic compound. It serves as an important structural scaffold and found in many natural and synthetic compounds, including several drugs, such as antipsychotic agents and antihistamines. This review article discusses the synthesis, pharmacological activities of azepine derivatives, and the structure–activity relationships (SAR) associated with them. The future prospects of azepine derivatives as therapeutic agents appear promising, as their diverse biological activities make them attractive candidates for the development of new drugs to treat various diseases.

Objective: This research presents the synthesis of fourteen novel coumarin derivatives, each fused with one of two distinct five-membered heterocycles, with the aim that these easily accessible coumarin frameworks will have a wide range of modifiable biomedical applications. Methods: The molecular structures of the synthesized derivatives were confirmed using spectroscopic methods, namely ¹H, ¹³C NMR, and FT-IR. The biomedical potential of these derivatives as antiproliferative, antioxidant, antidiabetic, anti-inflammatory, and antimicrobial agents was evaluated in vitro. Additionally, their biosafety toward non-infective bacterial strains and non-malignant cells was assessed. To investigate the pharmacokinetic and toxicological profiles of these derivatives, computational tools were employed. Results and Discussion: The authors identified the following key outcomes from the collected data. The type of fused heterocycle significantly influences the biomedical potential of the investigated derivatives. Compound A1 showed considerable anti-inflammatory activity via the lipoxygenase-dependent pathway and outperformed Nystatin in terms of antifungal potential. Compounds A2, A3, B2, and B3 exhibited great potential as antidiabetic candidates due to their potent glucosidase and amylase inhibitory properties. Compounds A4 and B4 demonstrated strong antioxidant, antiproliferative, and biosafety profiles. In terms of antibacterial activity, A5 and B5 were comparable to Ciprofloxacin against all the aerobic bacterial strains tested. Moreover, the biosafety profiles against non-infective bacterial strains were favorable for all the synthesized derivatives, particularly for this pair. Lastly, the synthesized derivatives exhibited favorable profiles regarding oral bioavailability and toxicity. Conclusions: These derivatives may serve as valuable building blocks for the future development of novel pharmaceuticals with a broad range of bioactivities.