Russian Journal of Bioorganic Chemistry最新文献

Objective: Oxidative stress plays a significant role in the development and progression of various neurodegenerative disorders, including aging, atherosclerosis, cancer, ischemia reperfusion, inflammation, rheumatoid arthritis, liver diseases. Additionally, it is implicated in retinal diseases (RD) such as glaucoma, diabetic retinopathy (DR), retinal vein occlusion (RVO), and age-related macular degeneration (AMD). In our study, we studied the therapeutic effect of oxyresveratrol, against H₂O₂-induced oxidative damage. Additionally, we investigated the role of estrogen receptors in the observed effects. Methods: Oxidative stress was induced by H₂O₂ in ARPE-19 cells. Oxyresveratrol was applied at seven different concentrations during and after oxidative stress. Besides, estrogen receptor inhibitors were applied 1 h before the treatment to investigate the role of estrogen receptors. Changes in cell viability were assessed using XTT. To investigate the effectiveness of oxyresveratrol at the molecular level, cell death detection, Caspase-3, and TOS measurement kits were employed. Results and Discussion: Our findings indicated that oxyresveratrol at concentrations of 10 and 100 µM reduced cell damage in ARPE-19 cells during and after-induced oxidative stress. Additionally, the therapeutic effect of oxyresveratrol in ARPE-19 cells during oxidative stress formation appeared to be dependent on estrogen receptors α and β, while the therapeutic effect after oxidative stress seemed to be GPER1-dependent. Furthermore, oxyresveratrol suppressed apoptosis in ARPE-19 cells under oxidative stress, reducing cell death, and both during and after oxidative stress, oxyresveratrol application decreased TOS levels. Although the antioxidant, anti-inflammatory, and neuroprotective effects of oxyresveratrol are well known, this is the first study to investigate its therapeutic effects on H₂O₂ induced oxidative stress in ARPE-19 cells and the involvement of estrogen receptors in these effects. Conclusions: We believe that oxyresveratrol may be an alternative therapy in the prevention and treatment of retinal diseases.

ve: Increasing tree productivity by genetic engineering methods is one of the main trends of forest biotechnology. A promising strategy for this is to improve the use efficiency of nitrogen, which is the main limiting factor of plant growth. For this purpose, the GS1 gene from Scots pine was transferred to downy birch (Betula pubescens) plants. This gene encodes the cytosolic form of glutamine synthetase, the main enzyme of nitrogen metabolism in plants. Methods: To assess the effects of insertion of this gene, the birch plant metabolome was analyzed using GC-MS and HPLC-MS. Results and Discussion: GC-MS analysis found 197 metabolites in birch extracts, but the metabolomes of two transgenic clones showed no statistically significant differences from the control. Using the S-plot based on the OPLS-DA model, 32 metabolite markers affecting the separation of control and transgenic birch plants were detected; 22 of them were identified. Three metabolites among them were nitrogen-containing, including γ-aminobutyric acid, the immediate precursor of which is glutamine. HPLC-MS analysis found 48 metabolites, but transgenic plants did not differ from the control. GC-MS, however, showed a decrease in the content of two phenolic compounds in transgenic plants, which is characteristic of improved nitrogen supply. Conclusions: The study shows that modification of nitrogen metabolism in birch plants does not significantly affect the biochemical composition of tree shoots.

Objective: The microencapsulation of Celecoxib (CXB) using different polymers aimed to enhance its solubility and permeability profile for potential neuroprotective applications in neurodegenerative diseases like Alzheimer’s disease. Methods: The solvent evaporation method was used for microencapsulation of CXB formulation. Characterization and evaluation of microencapsulation was done by FT-IR, DSC, XRD, SEM, and dissolution methods. Neuroprotective effect was evaluated by Scopolamine induced rat model. Results and Discussion: The solvent evaporation method yielded microencapsulated CXB formulations with high drug loading and improved dissolution profiles. Scanning electron microscopy revealed morphological changes, while differential scanning calorimetry and X-ray diffraction confirmed the conversion of CXB to an amorphous state post-encapsulation. Fourier-transform infrared spectroscopy indicated the formation of hydrogen bonds between CXB and polymers. In behavioral studies, microencapsulated CXB demonstrated superior efficacy in mitigating cognitive impairment induced by scopolamine, suggesting its potential as a neuroprotective agent. This effect may be attributed to the activation of cholinergic pathways. Conclusions: Thus, microencapsulation presents a promising strategy to enhance the therapeutic efficacy of CXB for neurodegenerative disorders.

Objective: Design, synthesis, characterization, and in silico studies of novel nitrobenzene thiazolyl hydrazones (VIa–VIh) and inhibitory action against the EGFR. Methods: All synthesized compounds were evaluated for their anticancer activity against selected cancer cell lines in vitro utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT assay and EGFR enzymatic assay. Target molecule features were investigated through a computational study that included drug-likeness, ADMET profiling, and molecular docking. Results and Discussion: The compounds (IVb), (IVe), and (IVh) showed prominent anticancer activity with an IC₅₀ value of 15.45, 18.23, 10.69 μM, and 12.75, 16.05, 11.95 μM against chosen cancer cell lines A549, and MCF-7 respectively. Additionally, in vitro EGFR enzymatic activity provided insight into the process of anticancer action of the majority of the active molecules. According to a molecular docking study, every molecule binds to EGFR (PDB ID: 5D41) with high affinities. Conclusions: Among all, derivatives (IVb), (IVe), and (IVh) showed moderate inhibition compared to different tested derivatives. Thus, the present study of all novel nitrobenzene thiazolyl hydrazones could be further optimized to develop new EGFR inhibitors.

Naturally occurring isocoumarins and dihydroisocoumarins emerged as a captivating class of compounds due to their structural diversity and multifaceted biological activities. It stands out as a group of metabolites, which are coumarin isomers with a reversed lactone moiety. They are synthesized by various organisms including plants, marine life, microbes, bacteria, and fungi. Our previous review covered the period 2016–2019, documenting nearly all natural products of this class. This updated review unravels the naturally occurring isocoumarins and dihydroisocoumarins by comprehensively exploring their structural elucidation and the broad spectrum of biological activities ranging from antimicrobial and anticancer properties to antitumour and enzyme inhibition. The classification and biological activities with structural elucidation revealed in our previous review are updated by the discovery of new members of this class. This review includes the most recent research on the structural variety and biological activity of these natural compounds.

Objective: Triazole, also known as pyrrdiazole, is a five-membered nitrogen-containing heterocyclic compound composed of two carbon atoms and three nitrogen atoms. Triazole analogs have garnered significant attention due to their extensive applications in medicinal chemistry and their diverse range of biological activities. Methods: With this consideration, we synthesized a diverse library of novel triazolopyridine-based 1,2,3-triazole derivatives (Xa–Xh) by employing Cu alkyne-azide cycloaddition methodology and confirmed the structures by various spectroscopic techniques including mass spectrometry, FT-IR, ¹H, and ¹³C NMR spectroscopy. Further, the synthesized compounds were evaluated for their in silico and in vitro antibacterial potential against various Gram-positive and Gram-negative bacterial strains. Results and Discussion: In the results it is found that compound (Xa) exhibited superior antibacterial activity against S. aureus while compound (Xd) demonstrated comparable activity against E. coli when compared to standard drugs. Molecular docking study also indicated that compounds (Xa) and (Xd) possess the capability to bind to the active sites of S. aureus, E. coli, and P. aeruginosa. Conclusions: All this findings suggested (Xa) and (Xd) as promising alternatives for combating bacterial infections.

Objective: The development of systems for targeted delivery of nucleic acids (NAs) is necessary to ensure their selective transport to the site of therapeutic action. The aim of this work was to synthesize carbohydrate-modified amphiphiles containing a spermine residue, required for compaction and binding to NAs, as well as a diglyceride residue for forming lipid aggregates and a carbohydrate residue (lactose or D-mannose) for improving the hydrophilic–lipophilic balance of the molecule. The lactose residue can serve as a targeting ligand for NA delivery into liver hepatocytes, and the D-mannose residue can perform specific NA transport into dendritic cells and macrophages. Methods: New carbohydrate-modified cationic amphiphiles were obtained by organic synthesis, and their aqueous dispersions or cationic liposomes were prepared. Cytotoxicity of the cationic amphiphiles and liposomes was performed using the MTT assay on HEK 293 and BHK cell lines in the absence of fetal bovine serum (FBS). Complexes of the cationic amphiphiles or liposomes with NAs (FITC-ODN, pDNA, and siRNA) were formed at various component ratios (N/P), and the efficiency of transfection in HEK 293 and BHK IR-780 cells was assessed by flow cytometry. Results and Discussion: New cationic amphiphiles containing lactose or D-mannose residues were synthesized. The cationic amphiphiles, whatever the structure of their carbohydrate residue, effectively deliver a short FITC-ODN into HEK293 cells in the presence of FBS, and are nontoxic. The cationic liposome formed by the lactose-containing amphiphile and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) successfully delivers short NAs (FITC-ODN and siRNA) both in the absence and in the presence of serum in the culture media. Conclusions: The obtained carbohydrate-modified cationic amphiphiles, both individually and as component of cationic liposomes, hold promise to be used as systems for the delivery of short nucleic acids in further development of drugs for gene therapy.

Objective: To examine the distribution of motility metrics of human mesenchymal stem cells (MSCs) and immortalized cell line in long-term 2D culture. Methods: We used single-cell motility tracking to analyze changes in the motility metrics (average speed, distance, track length). The study compared three cell lines: two lines of MSCs that undergo replicative senescence (DF-2, MSCWJ-1), and a third line of immortalized fibroblast-like cells with an unlimited lifespan (XP12RO). Results and Discussion: The results revealed that replicative senescence in MSCs is associated with an alteration in the distribution of observed motility metrics, which is expressed as a change from a bimodal distribution in young cells to a unimodal distribution in old cells. The distribution of motility metrics in immortalized cells did not change throughout long-term cultivation. Conclusions: Subpopulation heterogeneity decreases as MSCs undergo replicative senescence.

Objective: This study aims to explore the antimicrobial potential of thiazole derivatives and their significance as promising pharmaceutical agents, given their diverse therapeutic applications, including anticancer, antibacterial, antiviral, antihypertensive, and antifungal activities. Methods: An efficient synthetic route was established to synthesize a range of ethyl(E)-2-(4-hydroxy-3-((phenylimino)methyl)phenyl)-5-methylthiazole-4-carboxylate derivatives (VIIa–VIIj). Structural elucidation of these newly synthesized compounds utilized advanced techniques, such as ¹H, ¹³C NMR, FT-IR spectroscopy, mass spectrometry, and elemental analysis, ensuring accurate identification and characterization. Furhter, all the synthesized compounds were evaluated for their antimicrobial potential against various bacterial and fungal strains. Results and Discussion: In the results, it is found that compounds (VIIa), (VIId), (VIIe), and (VIIg) shows good antibacterial activity while compounds (VIIb) and (VIIc) shows good antifungal activity, suggesting their possible utility in clinical contexts. Conclusions: This research provides valuable insights into the therapeutic potential of thiazole derivatives, paving the way for future investigations into their clinical implications for addressing microbial challenges.

In response to infections, all jawed vertebrate organisms have evolved complex defense systems in which long-term immune memory of previous infections plays a central role. This memory allows the cells of the immune system to recognize pathogens and protect the organism by developing a stronger immune response in case of repeated infections with the same pathogen. Until recently, the long-term immune memory was attributed solely to the adaptive immune system. However, in the last decade, the protective role of innate immune cells has become increasingly apparent. It has been discovered that, in addition to their well-known role in short-term and nonspecific defense, these cells can also acquire a form of long-term memory, enabling them to mount an immune response to unrelated pathogens (heterologous protection), which is enhanced by repeated stimulation. This long-term nonspecific innate immune memory has been termed “trained immunity.” Its occurrence is associated with intensive metabolic rearrangements and epigenetic modifications of innate immune cells. In light of the growing threat of unforeseen epidemics, there is increasing hope that the possibility of creating nonspecific universal vaccines may be linked to the innate immune system. Recently, the capacity for trained immunity has been identified in tissue-resident immune cells. Moreover, the immune memory in non-immune cells, such as fibroblasts, stromal cells, and epithelial stem cells, has also been revealed. This ability has been termed “enhanced trained immunity” or “inflammatory memory.” The significance of tissue-specific induction of trained innate immunity is not yet fully understood, but it may play an important role in local defense against infections, as well as in inflammatory diseases and cancer.