Extremophilic microorganisms attract researchers by their unique characteristics, primarily antagonistic ones, acquired in the process of survival in extreme natural conditions. The antimicrobial potential of the metabolites of these microorganisms is quite broad, from the food industry to therapeutic drugs. Microbial mats of Lake Baikal are a source of unique and diverse microorganisms. The study aimed to evaluate the antimicrobial activity of bacterial strains isolated from the bottom sediments of the lake. Using heterotrophic growth conditions, seven bacterial strains were isolated from samples collected in several coastal zones of Lake Baikal. Thisstudy identified both widespread strains of the genera Pseudomonas and Bacillus and rare genera Micrococcus and Acinetobacterrepresentatives. Metabolites of five strains were found to have a broad spectrum of antimicrobial activity. Four large fractions of metabolites of the isolated strains wereidentified. Two peptides of the isolated fractions of metabolites (one is produced by microorganisms of all five isolated strains, another—only by Pseudomonas putida) are low molecular weight oligopeptides. These peptides were proved to be bacteriocins.
Directed formation of the structure of the culture of living cells is the most important task of tissue engineering. New materials for 3D scaffolds of living tissue are critical for the mass adoption of regenerative medicine protocols. In this manuscript, we demonstrate the results of the molecular structure study of collagen from Dosidicus gigas and reveal the possibility of obtaining a thin membrane material. The collagen membrane is characterized by high flexibility and plasticity as well as mechanical strength. The technology of obtaining collagen scaffolds, as well as the results of studies of its mechanical properties, surface morphology, protein composition, and the process of cell proliferation on its surface, are shown in the given manuscript. The investigation of living tissue culture grown on the surface of a collagen scaffold by X-ray tomography on a synchrotron source made it possible to remodel the structure of the extracellular matrix. It was found that the scaffolds obtained from squid collagen are characterized by a high degree of fibril ordering and high surface roughness and provide efficient directed growth of the cell culture. The resulting material provides the formation of the extracellular matrix and is characterized by a short time to living tissue sorption.
Aetiological and pathogenetic aspects in uterine cervix pathology associated with persistent viral infection by the high-risk human papillomavirus (HR HPV) are considered in this scientific review. The article provides a concise description of the biological structure and life processes of the virus. The main stages of uterine cervix impairment by the viral agent crucial for cancer development are described. Additionally, some mechanisms in the escape of viral progression from the immune control are given insight into. It is considered that, alongside with the aggression of the virus toward the host cells, there is a decline of cellular and humoral immunity in the female’s genitourinary tract, which may determine the growth and development of the neoplasm as well. The article puts a large emphasis on the defensive mechanisms appearing in the female organism as a response to the invasion and the persistence of the human papillomavirus. It is assumed that complete knowledge of pathogenetic mechanisms in development of oncogenic potential of the virus would imply the absence of rampant CIN and cervical cancer development induced by invasion of the agent into the organism
5 September 2024 in The Open Medicinal Chemistry Journal
Background: The biological activity of the new series of 1'H,5H-spiro[furan-2,4'-isoquinoline]-1',3',5(2'H)-triones and their selectivity for selenocysteine inspired us to create a QSAR model for design new thioredoxin reductase inhibitors. Method: Pharmacophore modelling, QSAR and PLS, Molecular descriptor calculation Results: The article provides an example of an analysis of the dependence of molecular descriptors and their relationship with the results of covalent docking for thioredoxin reductase. The constructed model makes it possible to predict the activity and selectivity of new electron-deficient olefins towards thioredoxin reductase. Conclusion: A small set of molecular descriptors of shape, charges on carbon atoms and energy values of molecular orbitals makes it possible to quickly calculate the concentration of half-inhibition of thioredoxin reductase and allows the selection of molecules for subsequent synthesis.
1 June 2026 in Applied Biochemistry and Microbiology
The relevance of researching the biotechnological potential of cyanobacteria is linked to an existing contradiction: despite extensive fundamental knowledge about the biotechnological potential of cyanobacteria, their commercial application is limited to a narrow niche. The key tasks in this regard are selecting highly productive strains or consortia and developing cultivation methods that increase the yield of target metabolites. Eight cyanobacterial cultures from the SPbU Science Park collection (CALU), isolated from various geographical regions, were reconstructed and characterized as cyanobacterial-bacterial consortia in terms of biomass growth and biochemical composition using standard methods of chemical composition analysis, factorial experiments, thin-layer chromatography, spectrophotometry, the clotting method, and 16S rRNA profiling. The results of two-step full factorial experiment showed significant variability in the total content of metabolites (proteins, carbohydrates, lipids, and pigments) but not biomass growth in different cultures when varying the photoperiod regime and/or the ratio of inorganic nitrogen and phosphorus (N/P) sources in the nutrient medium. Statistically significant anticoagulant activity was observed in the extracellular polymers in 5 of 8 cyanobacterial-bacterial consortia studied. These results suggest that further research should focus on the extracellular metabolites of cyanobacteria, as they are the most promising targets for commercial product development.
1 June 2026 in The Open Medicinal Chemistry Journal
Introduction: Thioredoxin reductase 1 (TrxR1) is a key enzyme involved in maintaining redox homeostasis in cancer cells and is considered a promising target for anticancer drug development. This study aimed to rationally design, synthesize, and evaluate a novel series of oxazol-5(4H)-one derivatives as potent and selective inhibitors of TrxR1. Methods: The design process was initiated by screening a commercial library of oxazolones, which informed the construction of a QSAR model. Guided by molecular docking studies against the TrxR1 catalytic site (PDB: 3EAN), a focused library of 18 target 4-benzylidene-oxazol-5(4H)-ones was synthesized via a multicomponent reaction using substituted hippuric acids and aromatic aldehydes. The inhibitory activity against TrxR1 and the off-target enzyme glutathione reductase (GR) was determined using a DTNB assay on A549 cell lysates. Cytotoxicity was evaluated against a panel of human cancer cell lines (A549, SHSY5Y, U251, and HELA) and normal HEK293T cells using an MTT assay. The mechanism of action was further investigated through immunoblotting analysis. Results: Several compounds demonstrated potent and selective TrxR1 inhibition. Lead compounds 1i, 1o, and 1s exhibited significant TrxR1 inhibition (over 50% at 25 µM) with low activity against GR. The IC 50 values for TrxR1 inhibition were in the nanomolar range (0.25 nM for 1i, 19.7 nM for 1o, and 4.2 nM for 1s). These compounds also showed pronounced cytotoxicity against cancer cells, with compound 1i being the most active against U251 glioblastoma cells (IC 50 = 12.58 µM) and demonstrating selectivity over normal cells. Immunoblotting analysis confirmed that inhibitors containing dual Michael acceptor motifs ( e.g ., 1q–s) induced the formation of covalent TrxR1 dimers, indicative of a unique mechanism of action. Discussion: The results validate our rational design strategy, highlighting the critical role of the Michael acceptor warhead and the oxazolone core in effective TrxR1 binding and inhibition. The high selectivity for TrxR1 over GR and the observed cytotoxic selectivity toward cancer cells underscore the therapeutic potential of this compound class. The discovery of TrxR1 dimerization provides a novel mechanism for irreversible enzyme inhibition. Conclusion: A new series of oxazol-5(4H)-one derivatives was successfully developed as highly potent and selective TrxR1 inhibitors. The lead compounds 1i, 1o, and 1s showed promising anticancer activity in vitro , coupled with a favorable selectivity profile. This work not only establishes a robust structure–activity relationship but also introduces a rational strategy for designing novel TrxR1-targeted antitumor agents, supported by the discovery of a dimerization-based inhibition mechanism.