Russian Journal of Bioorganic Chemistry最新文献

{"title":"Arylidene-Imidazolones as Antibacterial Agents Targeting Bacterial Replication and Translation","authors":"A. P. Chernyshova,&nbsp;M. A. Kryakvin,&nbsp;D. A. Lukyanov,&nbsp;O. A. Belozerova,&nbsp;A. V. Aralov,&nbsp;M. S. Baranov,&nbsp;V. A. Alferova","doi":"10.1134/S106816202660265X","DOIUrl":"10.1134/S106816202660265X","url":null,"abstract":"<p><b>Objective:</b> The rise of antibiotic resistance among bacterial pathogens poses a critical threat to modern medicine, driving the need for novel chemical scaffolds to develop antibacterial drugs with original mechanisms of action. Although arylidene-imidazolones, which form the structural core of the green fluorescent protein (GFP) chromophore, are widely used in bioimaging, their potential as drug precursors remains poorly understood. This work aimed to screen a library of 584 arylidene-imidazolone derivatives to identify compounds targeting bacterial replication and translation. <b>Methods:</b> Primary screening was conducted using the pDualRep2 reporter system and antibiotic-hypersensitive <i>Escherichia coli</i> strains. This approach enabled the simultaneous assessment of antibacterial activity and the collection of preliminary data on the mechanism of action. Based on these results, six candidate compounds were selected for subsequent mechanistic evaluation. <b>Results and discussion:</b> It was established that compounds <b>I</b> and <b>II</b> inhibit DNA polymerase I, whereas compounds <b>IV–VI</b> suppress bacterial translation in a cell-free system. <b>Conclusions:</b> The obtained results demonstrate that the arylidene-imidazolone framework represents a promising scaffold for the development of novel antibacterial agents.</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":"148926358","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":"Synergistic Activity of Antimicrobial Peptides with Orthogonal Mechanisms of Action","authors":"N. Z. Soboleva,&nbsp;S. O. Pipiya,&nbsp;A. I. Kalganova,&nbsp;V. A. Doroshenko,&nbsp;V. V. Starikova,&nbsp;D. O. Koroev,&nbsp;R. B. Gorodnichev,&nbsp;E. L. Vodovozova,&nbsp;I. V. Smirnov,&nbsp;S. S. Terekhov","doi":"10.1134/S1068162026603575","DOIUrl":"10.1134/S1068162026603575","url":null,"abstract":"<p><b>Objective:</b> The spread of multidrug-resistant (MDR) strains significantly limits the efficacy of existing antibiotics and necessitates the development of new therapeutic approaches. This problem is particularly relevant for Gram-negative ESKAPE pathogens, especially MDR strains of <i>Klebsiella pneumoniae</i>. Antimicrobial peptides (AMPs) can be considered promising alternative antimicrobial agents with high activity against MDR pathogen strains. Furthermore, the development of approaches based on the combined action of multiple AMPs or combinations of AMPs with classical antibiotics will allow a multiple potentiation of their antimicrobial action due to the synergistic effect of antimicrobial agents. We aimed to evaluate the synergistic action of AMPs with orthogonal mechanisms of action against MDR clinical isolates of <i>K. pneumoniae</i>, and to explore the translation of these synergistic principles to potentiate the clinically relevant glycopeptide antibiotic vancomycin. <b>Methods:</b> We utilized a screening approach based on the recombinant production of a panel of AMPs in the methylotrophic yeast <i>Pichia pastoris</i> to identify synergistic interactions. Promising synergistic combinations were subsequently validated <i>in vitro</i> using the checkerboard assay against clinical MDR isolates of <i>K. pneumoniae</i>. <b>Results and Discussion:</b> While individual recombinant AMP producers showed limited activity against clinical <i>K. pneumoniae</i> isolates, combining AMPs with distinct molecular targets resulted in pronounced synergistic effects. Unlike combinations of two membranolytic AMPs, pairing the membrane-disrupting peptide cecropin P1 with thanatin (an inhibitor of lipopolysaccharide transport) demonstrated true antimicrobial synergy, reducing individual minimum inhibitory concentrations fourfold. Furthermore, cecropin P1 effectively potentiated vancomycin (an antibiotic naturally inactive against Gram-negative bacteria), sensitizing MDR <i>K. pneumoniae</i> strains to this agent. <b>Conclusions:</b> Our findings demonstrate that combining orthogonal antimicrobial agents targeting at the membrane and cell wall components yields a universal synergistic effect. This approach provides a robust framework for developing highly effective antimicrobial regimens based on peptide synergy and the sensitization of MDR pathogens, thereby expanding the therapeutic spectrum of clinically vital antibiotics against drug-resistant infections.</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":"148926735","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":"Exploring the Influence of Plant Antifungal Defensin NaD1 on Immune Responses of Epithelial Cells and Macrophages","authors":"E. I. Finkina,&nbsp;S. I. Fateeva,&nbsp;О. V. Shevchenko,&nbsp;I. V. Bogdanov,&nbsp;A. A. Tagaev,&nbsp;T. V. Ovchinnikova","doi":"10.1134/S1068162026602533","DOIUrl":"10.1134/S1068162026602533","url":null,"abstract":"<p><b>Objective:</b> <i>Candida albicans</i> is a critical priority fungal pathogen and one of the most common causes of invasive candidiasis in immunocompromised patients. The high toxicity of existing antifungals and the spread of drug-resistant fungi create a need for new agents, for which antimicrobial peptides (AMPs) with both antifungal and immunomodulatory effects are promising candidates. <b>Methods:</b> In this study, we used real-time PCR and sandwich ELISA to investigate the immunomodulatory effects on epithelial and immune cells of the tobacco defensin NaD1, which exhibits fungicidal activity against <i>C. albicans</i>, as well as its modified analogs NaD1-2, NaD1-3, and NaD1-4 with reduced cytotoxicity. <b>Results and Discussion:</b> We demonstrate that NaD1 exerts immunomodulatory effects on a Caco-2 cell monolayer modeling the human intestinal epithelial barrier, and its action differs from that of the human β-defensin HBD2. In the absence of infection, NaD1 at a concentration of 2 μM activates epithelial immune defense after 4 h of cell stimulation by upregulating the expression of genes encoding CXCL8, cathelicidin LL-37, and the patternrecognition receptors Dectin1 and TLR9, while not affecting IL-1β production. Under <i>C. albicans</i> infection, NaD1 predominantly exhibits antiinflammatory properties. In contrast, the effect of HBD2 becomes pronounced upon prolonged stimulation (24 h) and is proinflammatory both in the presence and absence of infection. Furthermore, unlike the tobacco defensin, the modified NaD1 analogs show virtually no immunomodulatory effects and do not affect IL-1β production by THP-1-derived macrophages. Finally, the TLR2 inhibitor C29 and the TLR4 inhibitor C34 reduce the stimulatory effect of NaD1 on IL-1β production by macrophages. <b>Conclusions:</b> Thus, the tobacco defensin NaD1, unlike its modified analogues, exhibits immunomodulatory activities on human epithelial and immune cells, and the TLR2 and TLR4 receptors may be involved in mediating these effects.</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":"148926319","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":"Antibacterial Protein and Peptide Factors in Milk and Blood of Mammals: Interrelationships and Differences","authors":"D. A. Gasanova,&nbsp;D. A. Klimov,&nbsp;A. I. Levashova,&nbsp;L. V. Androsova,&nbsp;A. K. Fedorova,&nbsp;S. Yu. Zaitsev,&nbsp;P. A. Levashov","doi":"10.1134/S1068162026602491","DOIUrl":"10.1134/S1068162026602491","url":null,"abstract":"<p>At present, antibiotics remain widely administered to prevent bacterial infections in livestock. Therefore, antibiotics and their metabolites inevitably contaminate target food products, specifically meat and milk. This trend promotes the development of bacterial resistance, either multidrug or pandrug, across all therapeutic classes. This review presents a systematic examination of endogenous antibacterial factors in mammals, comparing their profiles and combined action in blood and milk. Lysozyme and lysozyme-related proteins, transferrins, antibacterial cationic peptides, milk protein hydrolysis products, and other endogenous agents are considered. These classes of antibacterial factors share two structural features: a net positive charge and the presence of hydrophobic (primarily aromatic) functional groups. Although their mechanisms of action against bacteria vary, both the synthesis and activity of these factors are strictly regulated by the host immune system. These structural properties and biochemical hallmarks facilitate the development of therapeutic agents based not only on xenobiotics but also on endogenous mammalian metabolites. More in-depth study of the antibacterial activity of proteins and peptides in both mammalian milk and blood is required to develop viable alternatives to conventional antibiotics.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928044","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":"Bacterial Antimicrobial Peptide Acidocin A Inhibits Growth of Clinically Relevant Pathogens","authors":"S. V. Balandin,&nbsp;E. I. Finkina,&nbsp;A. A. Kovrizhnykh,&nbsp;A. O. Guseinov,&nbsp;T. V. Ovchinnikova","doi":"10.1134/S1068162026602405","DOIUrl":"10.1134/S1068162026602405","url":null,"abstract":"<p><b>Objective:</b> The rise of antibiotic resistance necessitates exploring natural antimicrobial peptides like bacteriocins. This study aimed to investigate the anti-adhesive and anti-biofilm activities of acidocin A from <i>Lactobacillus acidophilus</i> against clinically relevant pathogens and its synergistic potential with nisin and human defensin HD-5. <b>Methods:</b> Recombinant peptides were obtained <i>via</i> heterologous expression in <i>Escherichia coli</i>. Anti-adhesive activity against <i>Candida albicans</i> was assessed on polystyrene using MTT assays and on Caco-2 monolayers by colony counting. Biofilm inhibition was tested against fungal and bacterial isolates, using resazurin and crystal violet, correspondingly. Synergy between the peptides was analyzed using checkerboard assays. <b>Results and Discussion:</b> Acidocin A inhibited <i>C. albicans</i> adhesion to polystyrene and Caco-2 model of intestinal epithelium. It effectively prevented biofilm formation by <i>C. albicans</i> and a number of bacterial strains, with inhibitory concentrations generally matching MICs. However, the peptide was inactive against mature biofilms. An additive effect of the peptide with human defensin HD-5 and acidocin 8912 was revealed. More importantly, acidocin A displayed synergism with nisin against <i>E. coli</i> (FICI 0.25–0.375), likely by permeabilizing the outer membrane to facilitate nisin entry. <b>Conclusions:</b> This study provides the first evidence of acidocin A’s anti-adhesive properties and efficacy in preventing biofilm formation by resistant pathogens. Its ability to synergize with nisin against Gram-negative bacteria highlights its potential for prophylactic and combination therapies.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928008","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":"Will Snake Venoms Help Overcome Antimicrobial Resistance?","authors":"A. V. Osipov,&nbsp;V. I. Tsetlin,&nbsp;Yu. N. Utkin","doi":"10.1134/S1068162026602417","DOIUrl":"10.1134/S1068162026602417","url":null,"abstract":"<p>Microbial resistance to drugs and the search for ways to overcome it are a global public health problem. It has now been established that the venoms of snakes from various families and genera are capable of suppressing the proliferation and killing resistant species and strains of microorganisms. This review focuses on the components of snake venom (toxins) that exhibit pronounced antimicrobial activity against pathogenic bacteria, fungi, and protozoa with known drug resistance, with indication of the resistant species and strain. The antimicrobial activity of enzymatic toxins (phospholipases A2, including enzymatically inactive homologues, L-amino acid oxidases, and metalloproteinases), toxins lacking enzymatic activity (proteins of the CRISP family, C-type lectins, and lectin-like proteins), polypeptides (three-finger toxins and Kunitz-type serine proteinase inhibitors), and cationic peptides (cathelicidins, crotamine, and omwaprin) is discussed. The problems of using snake venom toxins with antimicrobial activity and approaches to solve these problems are considered. Methods for increasing the efficacy and reducing the toxicity of such compounds are proposed: the use of bioinformatics and molecular modeling methods to identify active fragments of the molecule and design more effective synthetic analogues, encapsulation and nanoencapsulation. The immunomodulatory properties of toxins and their synergistic action with other antimicrobial substances are noted. Although currently the use of snake venom toxins is primarily at the research stage, they represent a promising reserve for the creation of new types of antimicrobial drugs capable of overcoming microbial resistance.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148927924","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":"β-Lactamase Inhibitors in Overcoming Bacterial Antibiotic Resistance","authors":"A. M. Egorov,&nbsp;M. M. Ulyashova,&nbsp;M. Yu. Rubtsova,&nbsp;M. G. Khrenova,&nbsp;A. E. Shchekotikhin","doi":"10.1134/S1068162026602454","DOIUrl":"10.1134/S1068162026602454","url":null,"abstract":"<p>The widespread prevalence of antibiotic-resistant pathogenic microorganisms that cause infectious diseases in humans and animals severely limits the possibilities of chemotherapy. Large families of enzymes play a key role in the various mechanisms of bacterial antibiotic resistance; in particular, resistance to β-lactam antibiotics in Gram-negative pathogens is due to the production of β-lactamases involving serine hydrolases and metalloenzymes. Due to the high cost of developing new antibacterial drugs, the main approach to overcoming bacterial antibiotic resistance is to combine β-lactams with β-lactamase inhibitors. This review analyzes information about two generations of inhibitors of this superfamily of enzymes: first-generation inhibitors are structural analogs of β-lactams and inhibit only class A serine β-lactamases. Second-generation inhibitors include compounds of the diazabicyclooctane class and boronic acid derivatives. They form complexes with β-lactamases that mimic the structure of acyl-enzyme complexes with antibiotics or the structure of the transition state of these complexes. Second-generation inhibitors are characterized by broader inhibitory specificity compared to first-generation inhibitors. Derivatives of cyclic boronic acids (oxoborines) have the broadest specificity for serine and metallo-β-lactamases. The development of new combinations of antibiotics with inhibitors that target various β-lactamases will restore the therapeutic efficacy of β-lactam antibacterial agents.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928045","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":"Production and Characterization of Recombinant Endolysin gp11 of Curtobacterium Bacteriophage Ayka","authors":"A. Yu. Yakimov,&nbsp;P. A. Levashov,&nbsp;M. M. Shneider,&nbsp;P. V. Evseev,&nbsp;A. A. Lukianova,&nbsp;A. D. Tokmakova,&nbsp;P. S. Arkhangelskaya,&nbsp;I. A. Ivanov,&nbsp;K. A. Miroshnikov,&nbsp;S. K. Komarevtsev","doi":"10.1134/S1068162026600698","DOIUrl":"10.1134/S1068162026600698","url":null,"abstract":"<p><b>Objective:</b> Bacterium <i>Curtobacterium flaccumfaciens</i> pv. <i>flaccumfaciens</i> is a Gram-positive pathogen causing bacterial wilt and tan spot of legumes. Organic agriculture requests for new biosafe antibacterials that can specifically target pathogenic bacteria without depressing beneficial bacterial bioadditives. Endolysin gp11 of the <i>Curtobacterium</i> phage Ayka could potentially be an active component of the new antibacterial agent to prevent wilt caused by <i>Curtobacterium flaccumfaciens</i> pv. <i>flaccumfaciens</i>. The goal of this work was to produce its recombinant form and to carry out an investigation of its biochemical properties. <b>Methods:</b> We performed bioinformatic analysis of phage Ayka lytic enzyme gp11 and obtained the expression construct based on the vector pEEva2 carrying the gp11 gene. This construction was used to transform <i>Escherichia coli</i> BL21(DE3)pLysS cells. Active purified form of endolysin gp11 was obtained as a result of combination of biomass extract fractionation with ammonium sulfate precipitation with subsequent metal-chelate chromatography of fractions containing target protein on Co-IDA-agarose. Bacteriolytic activity of gp11 was characterized by turbidimetry. <b>Results and Discussion:</b> Accumulation of the target enzyme occurred predominantly in insoluble form in inclusion bodies. The fraction of the active soluble form of the enzyme increased under lowtemperature conditions of protein synthesis. After purification the enzyme demonstrated high bacteriolytic activity against <i>C. flaccumfaciens</i> in a wide range of pH. Gp11 exhibited a wider range of activity compared to phage Ayka while remaining specific to the <i>Curtobacterium</i> genus. <b>Conclusions:</b> We obtained and characterized a recombinant form of <i>Curtobacterium</i> phage Ayka endolysin gp11. Its high activity and specificity can potentially help it find use as an antibacterial agent to prevent <i>C. flaccumfaciens</i> infections in legumes.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148927927","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":"Water-Mediated Synthesis, Antimicrobial Evaluation, Molecular Docking, and ADMET Profiling of Novel 2-Amino-3,5-dicarbonitrile-6-sulfanylpyridines","authors":"Sudha Rasmi Sudabattula,&nbsp;Rama Sekhara Reddy Dachuru,&nbsp;Mohan Gundluru,&nbsp;Kranthi Kumar Konidala,&nbsp;Suneetha Yeguvapalli","doi":"10.1134/S1068162025602782","DOIUrl":"10.1134/S1068162025602782","url":null,"abstract":"<p><b>Objective:</b> Herein, we describe a facile and efficient protocol for the synthesis of bioactive 2-amino-3,5-dicarbonitrile-6-sulfanylpyridines <i>via</i> a one-pot, multicomponent reaction of aldehydes, malononitrile, and thiophenols. The transformation is catalyzed by mild, readily accessible copper(II) triflate in an environmentally benign aqueous medium. <b>Methods:</b> The antimicrobial efficacy of the title compounds was evaluated against select bacterial and fungal strains using disc diffusion and minimum inhibitory concentration (MIC) assays. Advanced computational tools were deployed for comprehensive molecular docking and toxicogenomics profiling. Ensemble docking simulations were performed to elucidate the binding modes and affinity of the leading candidates within the active sites of glucosamine-6-phosphate (GlcN-6-P) synthase (PDB IDs: 2VF5 and 2POC). <b>Results and Discussion:</b> <i>In vitro</i> assays revealed robust antimicrobial activity, with derivatives <b>4i</b>, <b>4e</b>, <b>4d</b>, and <b>4j</b> exhibiting exceptional potency that outperformed or closely matched standard antibiotics. <i>In silico</i> ADMET evaluations validated that these target scaffolds possess highly promising drug-like attributes, optimal pharmacokinetic parameters, and clear compliance with established drug-likeness rules. <b>Conclusions:</b> The seamless integration of green synthesis, computational modeling, and biological validation highlights these 2-amino-3,5-dicarbonitrile-6-sulfanylpyridine hybrids as compelling lead candidates for multi-target therapeutic applications against invasive bacterial and fungal infections.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148750647","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":"Beyond Single Targets: A Review of Triazole-Thiazole Hybrids in Modern Drug Design","authors":"Prashant J. Burange,&nbsp;Pinkal H. Patel,&nbsp;Tejaswini P. Masne","doi":"10.1134/S1068162025603532","DOIUrl":"10.1134/S1068162025603532","url":null,"abstract":"<p>Triazole-thiazole hybrids represent highly privileged scaffolds in medicinal chemistry, characterized by exceptional structural versatility and a broad spectrum of pharmacological profiles, including anticancer, antimicrobial, antidiabetic, and anti-inflammatory activities. This review provides a critical overview of recent advancements in the synthesis, structure–activity relationships (SAR), and therapeutic applications of these dual-heterocyclic frameworks. We highlight strategic methodologies for integrating triazole and thiazole cores with complementary pharmacophores to enhance potency, optimize pharmacokinetic profiles, and circumvent multi-drug resistance. Furthermore, current optimization bottlenecks and emerging computational paradigms are systematically evaluated. Ultimately, this survey delineates key design principles for leveraging the modularity of triazole-thiazole scaffolds in the development of next-generation, multi-target directed ligands (MTDLs) against complex etiologies.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148750648","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}