Russian Journal of Bioorganic Chemistry最新文献

{"title":"Cinnamoylated Chitosan Derivatives Prepared via Reactive Extrusion: Structure–Property Relationships and Antifungal Activity","authors":"I. V. Shelomentsev,&nbsp;М. А. Khavpachev,&nbsp;V. V. Potseleev,&nbsp;P. L. Ivanov,&nbsp;M. Z. Bekanova,&nbsp;A. N. Zelenetskii,&nbsp;Т. А. Akopova","doi":"10.1134/S106816202660251X","DOIUrl":"10.1134/S106816202660251X","url":null,"abstract":"<p><b>Objective:</b> The aim of this work was to prepare cinnamoylated chitosan derivatives through solid-state reactive extrusion using cinnamic acid (CA) and cinnamoyl chloride (CC) as acylating agents, and to establish the relationships between the modification pathway, degree of substitution (DS), aggregate behavior, and antifungal activity. <b>Methods:</b> Mechanochemical modification was performed under solvent-free conditions in a co-rotating twin-screw extruder at 100°C for the CS–CA system and 60°C for the CS–CC system. The products were purified, fractionated in 2% acetic acid, and characterized using FT-IR spectroscopy, elemental analysis, and dynamic light scattering (DLS). Antifungal properties of the derived films were evaluated against Aspergillus niger on an agarized nutrient medium by measuring growth inhibition zones. <b>Results and Discussion:</b> FT-IR and elemental analysis revealed that modification with cinnamic acid occurs via both ionic (acid-base) interactions and covalent amide bond formation, whereas cinnamoyl chloride predominantly forms covalent amide bonds, resulting in covalent degrees of substitution of 0.14–0.34. DLS measurements showed that hydrophobic cinnamoyl modification promotes polymer self-organization, increasing supramolecular aggregate sizes from 555 nm (unmodified chitosan) up to 760–1300 nm for the derivatives. Increasing incorporation of cinnamoyl fragments progressively decreased derivative solubility in acidic media. <b>Conclusions:</b> <i>N</i>-Acylated chitosan derivatives with cinnamoyl fragments were successfully synthesized via a green, technologically efficient reactive extrusion method. The chemical nature of the acylating agent determines the precise structural modification pathway. Modified films exhibited distinct fungistatic activity against Aspergillus niger, with the most pronounced antifungal effect observed in the derivative featuring the highest degree of covalent substitution.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148926881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent Bacterial Infections: Molecular Mechanisms, Diagnostic Advances, and Preventive Strategies","authors":"A. V. Tutelyan,&nbsp;N. V. Vlasenko","doi":"10.1134/S1068162026603617","DOIUrl":"10.1134/S1068162026603617","url":null,"abstract":"<p>Persistent bacterial infections pose a critical challenge to global healthcare. Unlike their acute counterparts, persistent infections exhibit a prolonged, recurrent clinical course and marked recalcitrance to standard antibiotic therapies, driven by the bacterial capacity to transition into metabolic dormancy (persistence). This review synthesizes current insights into the molecular mechanisms governing persistence, evaluates cutting-edge diagnostic modalities for persister detection, and outlines promising eradication strategies. We delineate the pivotal pathways driving persister formation, focusing on type II toxin-antitoxin modules (e.g., MazEF, HipAB) and global stress response networks (the SOS response and RpoS regulon). Furthermore, we highlight how persisters actively evade host immunity <i>via</i> peptidoglycan remodeling and the induction of arginase-1, which depletes local L-arginine pools and suppresses T-cell functions. We systematically review emerging diagnostic platforms—spanning molecular, metabolic, immunological, microfluidic, and phage-mediated technologies—and address the clinical threat of convergent lineages, exemplified by hypervirulent and multidrug-resistant <i>Klebsiella pneumoniae</i>.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148926883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Escherichia coli Nissle 1917 in Cancer Bacteriotherapy: Functional Applications and Translational Challenges","authors":"N. Deeb,&nbsp;G. D. Otinov,&nbsp;E. I. Koshel","doi":"10.1134/S1068162026602120","DOIUrl":"10.1134/S1068162026602120","url":null,"abstract":"<p>Cancer bacteriotherapy has emerged as a strategy to exploit the natural ability of bacteria to interact with tumor tissue, but its development remains limited by the need to balance microbial activity with safety. <i>Escherichia coli</i> Nissle 1917 (EcN) has gained increasing attention as a probiotic bacterium that can be engineered for biological modulation, metabolic conversion, and hybrid therapeutic systems. This review discusses EcN in cancer therapy, focusing on its biological properties, tumor-colonization behavior, functional applications, and translational constraints. Overall, EcN offers a versatile framework for localized therapeutic strategies, but its clinical relevance will depend on better control of bacterial survival, therapeutic activity, and clearance.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148926819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Compounds of Plant Origin–Promising Agents in the Fight Against Antibiotic Resistance","authors":"Yu. I. Oshchepkova,&nbsp;A. M. Egorov","doi":"10.1134/S1068162026602569","DOIUrl":"10.1134/S1068162026602569","url":null,"abstract":"<p>Antimicrobial resistance (AMR), or antibiotic resistance of microorganisms, is becoming a global threat to healthcare, and strains with multidrug resistance (MDR) pose significant challenges for drug development programs. New mechanisms of antimicrobial traits render existing drugs ineffective, leading to prolonged illnesses and increased costs. The misuse of traditional and widely available antibiotics in healthcare, hygiene, veterinary medicine and agriculture is the main reason for the evolution, maintenance and alarming rate of spread of antimicrobial resistance. The continuing decline in antibiotic efficacy exacerbates the situation, necessitating urgent efforts by the global community aimed at developing innovative antibacterial drugs and treatments for infections caused by MDR pathogens. In addition to various natural and synthetic agents currently undergoing preclinical and clinical testing, secondary plant metabolites, or phytochemicals, are proving effective in combating drug-resistant strains. Various phytochemicals from classes such as alkaloids, phenolic derivatives, terpenoids, coumarins, organosulfur compounds and polypeptides have successfully demonstrated their antibacterial potential against MDR pathogens. Phytochemicals have been shown to be effective against molecular factors such as membranes, proteins, biofilms, efflux pumps and bacterial cell communication. However, despite promising results, further in-depth studies are needed to implement these approaches in clinical practice. The review examines successful examples, current challenges and prospects for the further application of phytochemicals in combating antimicrobial resistance of microbial pathogens.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148926734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activity Determinants in Linear Spider Venom Peptide Fragments Against MRSA","authors":"P. A. Mironov,&nbsp;A. А. Baranova,&nbsp;V. А. Alferova,&nbsp;D. E. Nolde,&nbsp;Z. О. Shenkarev,&nbsp;P. V. Dubovskii","doi":"10.1134/S1068162026601874","DOIUrl":"10.1134/S1068162026601874","url":null,"abstract":"<p><b>Objective:</b> Using neural networks, we previously identified linear fragments of spider venom peptides active against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA). Among them, peptide IX (IWLSLMKFAGKHL-NH₂) with a <i>C</i>-terminal amide displayed high antibacterial potency, whereas its non-amidated analogue, peptide X, was inactive. Peptide IX incorporates into zwitterionic multilamellar liposomes of dioleoylphosphatidylcholine (DOPC) without disrupting them, and also into anionic liposomes of dioleoylphosphatidylglycerol (DOPG) mimicking the MRSA cell membrane, leading to bilayer disruption. This study aims to elucidate the reasons for peptide X inactivation. <b>Methods:</b> According to ¹H NMR spectroscopy, peptide X in water is governed by the ionization of the His12 residue. ³¹P NMR data show that peptide X interacts with DOPC and DOPG membranes. Monte Carlo simulations revealed conformational differences between peptides IX and X upon interaction with an implicit membrane model. <b>Results and Discussion:</b> At pH 7.0 (net charge +2), peptide X aggregates, whereas at pH 5.0 (charge +3), it is monomeric. In contrast, peptide IX (+3 at pH 7.0 and +4 at pH 5.0) does not aggregate in this pH range. ³¹P NMR data show that peptide X has a weaker effect on bilayer packing than peptide IX and does not disrupt the bilayer in either case, consistent with its lack of anti-MRSA activity at pH 5–7. Monte Carlo simulations revealed conformational differences between peptides IX and X. We propose that the inactivation of peptide X arises from both reduced affinity and suboptimal binding to anionic bilayers, driven by aggregation in solution and weaker electrostatic peptide–membrane interactions. <b>Conclusions:</b> Thus, <i>C</i>-terminal amidation is a key modification required for anti-MRSA activity of short linear antimicrobial peptides.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148926736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of a Novel Fluoroquinolone and Its Interaction with Human Serum Albumin: Thermodynamic Parameters and Changes in the Secondary Structure of the Protein","authors":"I. G. Kolmakov,&nbsp;D. A. Grishin,&nbsp;E. K. Beloglazkina,&nbsp;R. L. Antipin,&nbsp;E. V. Kudryashova,&nbsp;А. А. Skuredina","doi":"10.1134/S1068162026602570","DOIUrl":"10.1134/S1068162026602570","url":null,"abstract":"<p><b>Objective:</b> A novel fluoroquinolone (PFQA) with biological activity was developed and obtained via a four-step synthesis. This study aimed to characterize its interaction with human serum albumin (HSA) and compare its binding efficiency and mechanism with other representatives of the fluoroquinolone class. <b>Methods:</b> The compound of interest was obtained by a four-step synthesis. Spectroscopic methods (fluorescence, FTIR, CD, etc.) were utilized to investigate PFQA complex formation with HSA. <b>Results and Discussion:</b> PFQA demonstrates moderate binding affinity to human serum albumin (K_binding = 3 × 10² M^–1) at site II (subdomain IIIA), as shown by fluorescence spectroscopy. According to thermodynamic parameters, the new compound forms a complex with the protein primarily through hydrophobic interactions. The introduction of a bulky hydrophobic substituent at position 3 of the fluoroquinolone does not cause significant conformational changes in albumin. The obtained results were compared with data for known representatives of fluoroquinolones of different generations in terms of the most important physicochemical and biological properties that must be considered for the design of new drug molecules. <b>Conclusions:</b> The characteristics obtained for PFQA correspond to the parameters of the fluoroquinolones used, suggesting similar pharmacokinetic parameters <i>in vivo</i>.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148926321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyoluteorin Production Drives the Antimicrobial-Potentiating Activity of Alpaca Oral Microbiota Components","authors":"L. T. D. Nguyen,&nbsp;A. A. Baranova,&nbsp;M. Yu. Zhitlov,&nbsp;G. P. Popova,&nbsp;A. M. Kudzhaev,&nbsp;E. A. Trusova,&nbsp;S. S. Sinel’nikova,&nbsp;G. Kh. Kudryakova,&nbsp;O. A. Belozerova,&nbsp;R. B. Gorodnichev,&nbsp;Yu. A. Ikhalainen,&nbsp;I. A. Rodin,&nbsp;V. A. Korshun,&nbsp;I. V. Smirnov,&nbsp;V. A. Alferova,&nbsp;S. S. Terekhov","doi":"10.1134/S1068162026602521","DOIUrl":"10.1134/S1068162026602521","url":null,"abstract":"<p><b>Objective:</b> The animal oral microbiota represents a promising reservoir of microorganisms that produce antimicrobial metabolites and compounds capable of modulating bacterial antibiotic sensitivity. Here, we aimed to screen the oral microbiota of alpacas to identify microbial strains exhibiting antimicrobial activity against Gram-negative and Gram-positive bacteria, fungi, and yeasts. <b>Methods:</b> To dissect the underlying antimicrobial mechanisms, we selected <i>Pseudomonas</i> isolates that displayed targeted activity against Gram-negative bacteria and subjected them to metabolomic profiling. <b>Results and Discussion:</b> The analysis revealed that this antimicrobial activity is driven by the production of pyoluteorin, a membrane-active metabolite. Although pyoluteorin alone exhibited limited antimicrobial efficacy, it strongly potentiated the action of clinically relevant antibiotics. Notably, at a sub-cytotoxic concentration of 1.5 μg/mL (IC₅₀ = 2.0 ± 0.3 μg/mL), pyoluteorin sensitized antibiotic-resistant <i>Klebsiella pneumoniae</i> strains, enhancing their susceptibility to the membrane-disrupting antibiotic polymyxin B by an order of magnitude. <b>Conclusions:</b> The future development of bacterio-selective membrane-active agents will facilitate the deployment of such synergistic approaches for the emergency treatment of infectious diseases caused by multidrug-resistant pathogens.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148926497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modern Challenges of Antimicrobial Resistance and Innovative Approaches to the Treatment of Bacterial Infections","authors":"N. L. Klyachko,&nbsp;I. M. Le-Deygen,&nbsp;N. A. Kozyrev,&nbsp;R. M. Gendenov,&nbsp;E. A. Maryashina,&nbsp;A. V. Lopukhov","doi":"10.1134/S1068162026603605","DOIUrl":"10.1134/S1068162026603605","url":null,"abstract":"<p>The global expansion of antimicrobial resistance poses a formidable threat to public health. Ongoing bacterial evolution and phenotypic adaptation progressively render conventional antimicrobial strategies resource-intensive and less efficacious, while concurrently exacerbating treatment-associated adverse effects. Consequently, there is an imperative demand to refine existing therapeutic modalities, implement synergistic combinations, and pioneer fundamentally novel strategies to combat infections precipitated by multidrug-resistant pathogens. This review delineates the primary molecular mechanisms governing bacterial resistance and underscores the clinical impact of key infectious diseases. The cornerstone of this work lies in a comprehensive analysis of both canonical and innovative paradigms in antibacterial therapy. By synthesizing state-of-the-art scientific data, this paper provides a definitive perspective on the most promising frontiers in infectious disease management.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148926377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of Drug Resistance Mechanisms: Integration of Molecular Modeling and Artificial Intelligence Methods","authors":"M. G. Khrenova,&nbsp;M. Yu. Rubtsova,&nbsp;A. M. Egorov","doi":"10.1134/S1068162026602600","DOIUrl":"10.1134/S1068162026602600","url":null,"abstract":"<p>Drug resistance caused by single-point amino acid substitutions in target proteins represents a serious problem in modern therapy of oncological, infectious and viral diseases. This review systematizes modern computational modeling methods that allow studying the molecular mechanisms of such resistance and predicting its emergence. Contemporary databases and machine learning tools used for resistance prediction from genomic data are analyzed. The potential of the emerging direction of physics-informed artificial intelligence models for enhancing the interpretability of predictions is noted.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148926373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highly Effective Lysozyme-Based Antibacterial Compositions Containing Activating Additives","authors":"A. R. Egorov,&nbsp;D. A. Klimov,&nbsp;P. A. Levashov","doi":"10.1134/S1068162026602582","DOIUrl":"10.1134/S1068162026602582","url":null,"abstract":"<p><b>Objective:</b> This study evaluates established low-molecular-weight activators of lysozyme and reports a novel lysozyme-based antibacterial composition containing charged amino acids and a pharmaceutically acceptable surfactant. These compounds exhibit biocompatibility and safety, both individually and in combination. <b>Methods:</b> The bacteriolytic effect of the composition was tested on live bacteria from various families, specifically, <i>Micrococcus luteus</i> (non-pathogenic Gram-positive cocci with some similarity in cell wall structure to pathogenic streptococci and staphylococci), <i>Escherichia coli</i> (a Gram-negative rod-shaped bacterium, a non-pathogenic analogue of the causative agents of salmonellosis, typhoid fever, bacterial dysentery, and plague), and <i>Priestia megaterium</i> (spore-forming Gram-positive bacilli, a non-pathogenic analogue of the causative agent of anthrax). <b>Results and Discussion:</b> This antibacterial composition can be used to kill bacteria on various surfaces in public places and at home, including antibiotic-resistant bacteria, since the mechanism of its antibacterial action is fundamentally different from that of antibiotics. <b>Conclusions:</b> The constituents of the proposed antibacterial composition also have the potential to be developed into food supplements. Our findings provide a basis for enhancing the antibacterial activity of lysozyme within the body, both in extracellular biological fluids and within the lysosomes of immune cells, which are responsible for the destruction of pathogenic cells and antigen presentation, followed by the regulation of antibody synthesis.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148926320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}