Russian Journal of Bioorganic Chemistry最新文献

{"title":"Changes in the Protein Composition of the Exiguobacterium sibiricum Membrane with Decreasing Temperature: A Proteomic Analysis","authors":"L. E. Petrovskaya,&nbsp;R. H. Ziganshin,&nbsp;E. A. Kryukova,&nbsp;E. V. Spirina,&nbsp;E. M. Rivkina,&nbsp;S. A. Siletsky,&nbsp;D. A. Dolgikh,&nbsp;M. P. Kirpichnikov","doi":"10.1134/S1068162025601995","DOIUrl":"10.1134/S1068162025601995","url":null,"abstract":"<p><b>Objective:</b> The psychrotrophic Gram-positive bacterium <i>Exiguobacterium sibiricum</i>, isolated from Siberian permafrost deposits, grows over a wide temperature range and remains viable after prolonged cryopreservation. To study its adaptation to environmental conditions, we investigated changes in the membrane proteome of the cells grown in a poor medium at 10°C. <b>Methods:</b> Proteins of the membrane fraction isolated from <i>E. sibiricum</i> were analyzed using the label-free quantitative liquid chromatography- tandem mass spectrometry. <b>Results and Discussion:</b> Comparison of the samples from the cells cultured at 10°C and at room temperature revealed significant differences in the content of many proteins involved in important physiological processes, including DNA and RNA binding proteins, membrane transporters, proteins providing protection against osmotic and oxidative stress, and others. <b>Conclusions:</b> The results of this study contribute to understanding of the mechanisms of the processes occurring in the cell membranes of psychrotrophic bacteria at low temperatures, and complement the existing views on the adaptation strategies of microorganisms living in permafrost deposits. The data obtained can also be used to search for potential biocatalysts with activity at low temperatures.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"2000 - 2013"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181407","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":"Targeted Nanoliposomes Loaded with IR780 Dye as a Multifunctional Nanoplatform for Photothermal and Photodynamic Cancer Therapy","authors":"G. M. Proshkina,&nbsp;E. I. Shramova,&nbsp;A. S. Sogomonyan,&nbsp;S. M. Deyev","doi":"10.1134/S1068162025601879","DOIUrl":"10.1134/S1068162025601879","url":null,"abstract":"<p><b>Objective:</b> During cancer treatment, the combined effect of photothermal therapy (PTT) and photodynamic therapy (PDT) has unique advantages over each of these methods alone. However, two lasers with different wavelengths are usually required to achieve the synergistic effect of PDT/PTT. In this study, we developed a multifunctional targeted nanoplatform for simultaneous combined photothermal and photodynamic therapy under 808 nm near-infrared laser irradiation. <b>Methods:</b> Small liposomes (~140 nm) specific to the tumor-associated antigen HER2 and loaded with near-infrared heptamethine cyanine dye IR780 were prepared. The targeting of liposomes to HER2 is mediated by the HER2-specific scaffold protein DARPin_9-29 located on the outer surface of liposomes. Tumor targeting of DARP-Lip(IR780) was evaluated <i>in vitro</i> using flow cytometry and confocal microscopy. The photothermal and photodynamic effects as well as cellular cytotoxicity of HER2-specific liposomes loaded with IR780 were evaluated <i>in vitro</i> under near-infrared light irradiation. <b>Results and Discussion:</b> It was established that IR780, when loaded in liposomes, retains photothermal and photodynamic properties: upon irradiation, the temperature of IR780-loaded liposome solution rapidly increases (up to 60°C within 60 s), and the production of reactive oxygen species is also detected. <i>In vitro</i> experiments demonstrated that HER2-specific liposomes containing IR780 exhibit photoinduced cytotoxicity against HER2-overexpressing cells, causing death of 50% of the cell population at a concentration of 2.85 μM. <b>Conclusions:</b> The results of this study suggest that HER2-specific liposomes containing IR780 have excellent targeted characteristics, and IR780 can be used as an active agent for simultaneous photothermal and photodynamic therapy.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"1954 - 1961"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1134/S1068162025601879.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, Anticancer and EGFR Inhibitory Activity of Novel Benzo[b][1,4]oxazine-1,3,4-oxadiazolo-1,2,3-triazoles","authors":"Vishweshwar Punna,&nbsp;Jeshma Kovvuri,&nbsp;Y. Umeshwar,&nbsp;Maheshwar Kundarapu","doi":"10.1134/S1068162025600497","DOIUrl":"10.1134/S1068162025600497","url":null,"abstract":"<p><b>Objective:</b> This study involves the design, synthesis, characterization, and both <i>in vitro</i> and <i>in silico</i> evaluation of novel benzo[<i>b</i>][1,4]oxazine-1,3,4-oxadiazolo-1,2,3-triazoles (<b>VIIIa–VIIIo</b>) and their inhibitory action against EGFR. <b>Methods:</b> All synthesized compounds were evaluated for their anticancer activity against selected cancer cell lines <i>in vitro</i> using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the EGFR enzymatic assay. More potent compounds were further screened for their <i>in silico</i> molecular docking. <b>Results and Discussion:</b> ESI-MS, ¹H, and ¹³C NMR spectroscopy confirmed the identity of all prepared derivatives. Compound (<b>VIIIi</b>) exhibited more potent activity against MCF-7 cancer cells with an IC₅₀ value of 4.22 ± 0.31 μM. Additionally, compound (<b>VIIIk</b>) demonstrated equipotent activity against both MCF-7 and A-549 cell lines, with IC₅₀ values of 4.89 ± 0.26 and 5.48 ± 0.32 μM, respectively. These results were compared to the standard erlotinib. Further evaluation of the EGFR inhibitory activity of the more potent compounds revealed that compounds (<b>VIIIi</b>) and (<b>VIIIk</b>) exhibited significant activity. All potent compounds showed higher binding energies compared to the standard erlotinib. Conclusions: A series of benzo[<i>b</i>][1,4]oxazine-1,3,4-oxadiazolo-1,2,3-triazoles were synthesized and investigated for <i>in vitro</i> anticancer activity. Some compounds showed excellent efficacy against MCF-7 and A-549 cell lines. The more potent compounds were less harmful to the normal HEK293 cell line. Compounds (<b>VIIIi</b>) and (<b>VIIIk</b>) demonstrated potent EGFR inhibitory activity compared to the standard. Finally, slight modifications to the potent compound (<b>VIIIi</b>) could make it a promising future therapeutic candidate for cancer treatment. All potent compounds exhibited significant binding energies, ranging from ­–9.77 to –10.97 kcal/mol, compared to the standard erlotinib (­–7.69 kcal/mol).</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"2261 - 2273"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181450","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":"Construction of a Producer Strain of the Fibrinolitic Enzyme PAPC Based on Pichia pastoris Yeast","authors":"S. K. Komarevtsev,&nbsp;Yu. S. Lapteva,&nbsp;R. H. Ziganshin,&nbsp;V. V. Farofonova,&nbsp;V. N. Stepanenko,&nbsp;A. A. Osmolovskiy,&nbsp;K. A. Miroshnikov,&nbsp;E. V. Loktyushov","doi":"10.1134/S1068162025602046","DOIUrl":"10.1134/S1068162025602046","url":null,"abstract":"<p><b>Objective:</b> Yeast <i>Pichia pastoris</i> (<i>Komagataella phaffii</i>) is widely used in food and pharmaceutical industries as microbial cell factories of recombinant proteins. Protease-activator of protein C (PAPC) of blood plasma from <i>Aspergillus ochraceus</i> VKM F-4104D micromycetes can potentially be introduced into therapeutic practice as a fibrinolytic drug and into diagnostic systems for blood coagulation analysis as the main component that activates protein C. The aim of this work was to construct a PAPC-producing strain based on <i>P. pastoris</i> and to demonstrate the effective production and secretion of the recombinant enzyme into the culture medium. <b>Methods:</b> We assembled a pD912-AFSnoEAEA-PAPC vector carrying the <i>papc</i> gene under a methanol-induced AOX1-promoter. This vector was used to transform <i>P. pastoris</i> yeast, and transformants were selected on a zeocin-containing medium. The clones most effectively producing the target enzyme were selected using an agar medium with casein and an analysis of the culture medium by SDS-PAGE. <b>Results and Discussion:</b> The selected clones secreted an active form of PAPC into the culture medium. The ability to production of the target enzyme remained after 60 generations. LC-MS analysis confirmed the presence of the enzyme in the culture medium and demonstrated that accumulation occurs in the mature active form. <b>Conclusions:</b> We demonstrated that <i>P. pastoris</i> system can be successfully used for the high-level expression of PAPC from <i>A. ochraceus</i>. The low amount of host cell proteins in the culture medium makes the subsequent purification of the target enzyme easier in comparison to bacterial expression systems. The obtained strain can be used for the further production of experimental industrial batches of the enzyme in biotechnological production facilities that support yeast fermentation.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"2022 - 2033"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181451","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":"RNA Interference as a Method for Validation of Pharmacological Targets in Fibrosis Treatment","authors":"A. S. Mikaelyan,&nbsp;N. Halimani,&nbsp;V. V. Fedorova,&nbsp;Yu. V. Kotelevtsev","doi":"10.1134/S1068162025602150","DOIUrl":"10.1134/S1068162025602150","url":null,"abstract":"<p>RNA interference (RNAi) is an evolutionarily conserved mechanism of gene expression silencing based on the degradation of mRNA by small interfering RNAs (siRNAs). The discovery of this mechanism has not only become a powerful tool for fundamental research in biology, but has also opened up new perspectives for therapeutic medicine. In terms of efficacy and safety, siRNA therapy represents a promising alternative to traditional pharmaceutical approaches, which are often characterized by systemic toxicity and low specificity. siRNA-based therapy allows for the selective suppression of genes associated with pathologies, providing high specificity and low toxicity. The use of siRNA to modulate the activity of macrophages, key effectors of innate immunity that play a central role in the development of liver fibrosis, represents particular interest. Due to their high plasticity, macrophages are able to polarize into proinflammatory (M1) or anti-inflammatory (M2) phenotypes, which determines their contribution to the progression or regression of fibrosis. Suppression of key polarization regulators (such as <i>EGR2</i>, <i>IRF5</i>, <i>IRF3</i>, <i>TLR4</i>, <i>HAS2</i>) using siRNA allows macrophage repolarization into alternative functional phenotypes. This review systematizes current data on the role of macrophages in the pathogenesis of liver fibrosis and the prospects for using siRNA therapy to control their activity. Strategies for precision targeting of key molecular targets are discussed, opening up new possibilities for the development of pathogenetically justified treatment methods.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"1853 - 1862"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1134/S1068162025602150.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an Experimental Intracranial PDX Model of Human Glioblastoma in NSG Mice","authors":"N. V. Antipova,&nbsp;D. A. Bondarenko,&nbsp;D. V. Mazur,&nbsp;A. A. Isakova,&nbsp;M. E. Gasparian,&nbsp;O. I. Patsap,&nbsp;V. M. Pavlov,&nbsp;E. S. Mikhailov,&nbsp;N. A. Goryacheva,&nbsp;D. I. Rzhevsky,&nbsp;S. G. Semushina,&nbsp;D. A. Dolgikh,&nbsp;A. N. Murashev,&nbsp;A. V. Yagolovich","doi":"10.1134/S1068162025602514","DOIUrl":"10.1134/S1068162025602514","url":null,"abstract":"<p><b>Objective:</b> Establishment of an orthotopic intracranial model from human glioblastoma cell culture in immunodeficient mice is important both for studying the invasiveness and aggressiveness of tumor cells and for developing a reliable model for assessing the effectiveness of new drugs for glioblastoma therapy. The aim of this work was to perform a comparative study of tumorigenicity of established and primary patient-derived glioblastoma cells during subcutaneous and orthotopic intracranial xenotransplantation into immunodeficient NSG mice. <b>Methods:</b> The glioblastoma cell line U87MG and primary patient-derived glioblastoma cells (022 culture) were characterized in terms of morphology and molecular subtype. The expression of specific markers was analyzed by RNA-seq. Cells were xenografted into immunodeficient NSG mice either subcutaneously or orthotopically into the corpus striatum. Tumors were examined using immunohistochemical staining for glial markers. <b>Results and Discussion:</b> It was shown that in both groups of animals with orthotopic xenografts, tumors grew both deep into the brain tissue and on the brain surface, and in the case of the primary 022 culture, growth toward the ventricles was also noted. Morphologically, primary 022 cells had an epithelioid morphology, while U87MG cells were more sarcomatoid. Importantly, the U87MG cell line was tumorigenic in both localizations. However, the primary 022 culture formed tumors only during intracranial, but not during subcutaneous xenotransplantation, which indicates the neurospecificity of this model. <b>Conclusions:</b> The primary patient-derived glioblastoma culture 022 may serve as a more relevant model of glioblastoma compared to the U87MG cell line-based model.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"2034 - 2040"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181452","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":"Influence of Cultivation Conditions on Expression of Transcription Factor Genes in Glioblastoma Cells","authors":"A. I. Rezekina,&nbsp;D. V. Mazur,&nbsp;M. I. Shakhparonov,&nbsp;N. V. Antipova","doi":"10.1134/S1068162025601909","DOIUrl":"10.1134/S1068162025601909","url":null,"abstract":"<p><b>Objective:</b> Glioblastoma is a malignant and aggressive brain tumor characterized by deregulation of certain transcription factors. One of its main traits, cellular heterogeneity, probably originates from tumor stem cells, a treatment-resistant and poorly differentiated cell population capable of continuous proliferation and formation of phenotypically distinct cells. The exceptional adaptive abilities and drug resistance of glioblastoma result from peculiarities of gene expression in tumor cells. Studying the expression of key transcription factors and mechanisms of tumor stem cell differentiation can help identify molecular pathways important for glioblastoma therapy. <b>Methods:</b> Changes in expression of transcription factors <i>MYCN</i>, <i>MYCC</i>, <i>PHOX2A</i>, and <i>PHOX2B</i>, which are involved in cell cycle regulation and differentiation, were evaluated using real-time PCR in response to changes in cultivation conditions. <b>Results and Discussion:</b> Primary cultures grown in medium with fetal bovine serum acquired morphology and gene expression similar to cell lines. Moreover, all cell lines and primary cultures of glioblastoma under standard conditions differed in expression profiles of the studied genes. Primary cultures with the proneural subtype demonstrated higher <i>PHOX2A</i> expression than tumors with the mesenchymal subtype. Often, <i>PHOX2B</i> expression was not detected. Interestingly, in response to changes in cultivation conditions, all lines and cultures demonstrated multiple increases in <i>MYCN</i> expression, as well as opposite responses of <i>PHOX2A</i> and <i>PHOX2B</i>. <b>Conclusions:</b> Under the new conditions, there is a shift away from the initial molecular parameters of the tumor toward less accurate <i>in vitro</i> models of glioblastoma—cell lines. Moreover, changes in <i>MYCN</i>, <i>PHOX2A</i>, and <i>PHOX2B</i> expression in response to altered cultivation conditions indicate a possible role of these genes in glioblastoma stress resistance, making them important targets for further research to identify therapeutic targets for glioblastoma.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"1962 - 1969"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1134/S1068162025601909.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Ionizable Cationic Lipid for Intracellular RNA Delivery","authors":"K. Sh. Gaisin,&nbsp;E. V. Ryabukhina,&nbsp;D. O. Koroev,&nbsp;I. I. Mikhalyov,&nbsp;E. S. Zhuravlev,&nbsp;G. A. Stepanov,&nbsp;I. A. Boldyrev,&nbsp;E. L. Vodovozova","doi":"10.1134/S1068162025602149","DOIUrl":"10.1134/S1068162025602149","url":null,"abstract":"<p><b>Objective:</b> Ionizable lipids are a key component of the lipid nanoparticle platform for RNA therapy. They ensure efficient assembly of a lipid-nucleic acid complex, protect it against premature degradation, and after endocytosis, promote the release of RNA into the cytoplasm for further processing. Despite the multiple proposed ionizable cationic lipids, the search for molecules to improve the efficacy and safety profile of lipid nanoparticles (LNPs) for RNA delivery continues. <b>Methods:</b> The paper describes the synthesis of a new ionizable cationic lipid that is a diglyceride derivative of tertiary alkylamine, [5-[1,2-di(decanoyloxy)propane-3-yloxy]pentyl-(4-hydroxybutyl)-amino]pentoxy]-2-decanoyloxypropyl]decanoate (An-1). Lipid An-1, along with the common so-called helper lipids, was used to formulate LNPs with mRNA of the green fluorescent protein. The functional activity of the LNPs with mRNA-GFP was tested in a culture of human embryonic kidney cells HEK293T. <b>Results and Discussion:</b> The synthesis of An-1 is characterized by simplicity and cost-effectiveness of reagents. Comparative experiments with the lipid ALC-0315 have shown that An-1 lipid forms LNPs similar in size and incorporation efficiency of the model mRNA. The LNPs containing mRNA-GFP, formulated with An-1 lipid, transfected cells more efficiently than those formulated with ALC-0315 lipid. <b>Conclusions:</b> A new ionizable cationic lipid was synthesized. Its molecule does not contain branched alkyl chains whose metabolism is difficult. This may be the reason for effective transfection of RNA-LNPs comprising An-1. It is assumed that the new ionizable lipid can be used in the production of mRNA vaccines.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"1982 - 1989"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1134/S1068162025602149.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modern Laboratory Test-Systems as Platforms for Validation of Clinically Promising T-Cell Receptors","authors":"R. V. Mungalov,&nbsp;N. S. Vand,&nbsp;D. M. Chudakov,&nbsp;E. A. Bryushkova","doi":"10.1134/S1068162025601910","DOIUrl":"10.1134/S1068162025601910","url":null,"abstract":"<p>The development of therapeutic antigen-specific T-cell receptors (TCRs) requires comprehensive preclinical validation of their functional activity. One of the approaches in the development of new drugs for cell therapy based on antigen-specific T lymphocytes is the modification of autologous T lymphocytes with endogenous T-cell receptors. The present work reviews modern laboratory platforms used to assess key TCR characteristics: immunological synapse formation, specificity and affinity of antigen binding, activation of signaling pathways, cytokine production and cytotoxic potential. Particular attention is paid to the creation of model T-cell lines expressing transgenic TCRs, optimization of HLA context of target cells and application of multiparametric technologies for immune response analysis. The prospects of using 3D organoid models for validation of functional activity of transgenic TCRs under conditions close to physiological ones, as well as for predicting their clinical efficacy are discussed. The presented approaches form the basis for rational selection of candidate receptors for their subsequent application in immunotherapy of tumors and chronic infections.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"1827 - 1837"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1134/S1068162025601910.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactive Coumarins: Bioorganic Strategies for Targeting Enzymes, Receptors, and DNA","authors":"Yasser Fakri Mustafa","doi":"10.1134/S1068162025601788","DOIUrl":"10.1134/S1068162025601788","url":null,"abstract":"<p>Coumarins, a structurally diverse class of naturally occurring and synthetic compounds, have emerged as pivotal entities in modern bioorganic chemistry. Centered around the 2<i>H</i>-1-benzopyran-2-one scaffold, these molecules exhibit remarkable structural plasticity, enabling fine-tuned interactions with a broad spectrum of biological targets, including enzymes, nucleic acids, and cellular receptors. This review provides a detailed overview of bioactive coumarins and their growing importance as molecular modulators and scaffolds in drug discovery and design. Special emphasis is placed on their dual role as both therapeutic agents and diagnostic probes, capable of engaging in covalent and non-covalent interactions within biological systems. The discussion highlights how strategic structural modifications enhance coumarins’ specificity and potency toward key biological macromolecules. Mechanistic insights into coumarin-based enzyme inhibition are explored, particularly with respect to active and allosteric site binding, using representative examples involving dehydrogenases, DNA repair enzymes, and cytoskeletal proteins. Furthermore, the review delves into the interaction of coumarins with nuclear receptors, such as estrogen, glucocorticoid, and peroxisome proliferator-activated receptors, elucidating their roles in modulating neurological, cardiovascular, and immunological functions. Special attention is given to the nucleic acid-binding potential of coumarins, particularly their involvement in DNA intercalation and G-quadruplex stabilization, which are promising strategies in anticancer therapy. The review also examines recent advances in sustainable synthetic methodologies, including microwave-assisted and green chemistry approaches. Analytical tools like fluorescence spectroscopy and chromatographic techniques are emphasized for their critical role in evaluating structure–activity relationships and biological responses. Finally, the pharmacokinetic behavior, safety considerations, and emerging nanotechnology-enabled delivery systems are discussed. <i>In vivo</i> and clinical findings underscore the translational relevance of coumarins, particularly in oncology, infectious diseases, and neurodegenerative conditions. Looking ahead, coumarins stand out as versatile molecular platforms with immense potential to inspire innovative therapeutic strategies through interdisciplinary collaboration.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"2304 - 2335"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181470","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}