Russian Journal of Bioorganic Chemistry最新文献

{"title":"Harnessing Artificial Intelligence to Discover the Therapeutic Potential of Natural Coumarins: A Review Study","authors":"Nameer Mazin Zeki,&nbsp;Yasser Fakri Mustafa","doi":"10.1134/S1068162024607225","DOIUrl":"10.1134/S1068162024607225","url":null,"abstract":"<p>Natural coumarins, a group of bioactive phytochemicals, exhibit a wide range of biological activities, including anticancer, anti-inflammatory, antimicrobial, and antioxidant effects. Owing to their structural diversity and pharmacological properties, coumarins have long attracted scientific interest. This review discusses the emerging role of artificial intelligence (AI) in advancing coumarin-related research and drug discovery. AI-based approaches, such as machine learning and deep learning, are increasingly used to analyze large datasets, predict biological activity, and identify coumarin derivatives with promising therapeutic potential. Furthermore, computational tools like virtual screening and molecular docking facilitate the modeling of coumarin interactions with biological targets, providing valuable insights into their mechanisms of action and potential applications in personalized medicine. AI also significantly accelerates drug discovery by improving structure–activity relationship (SAR) analyses and optimizing lead compounds for preclinical and clinical evaluation. The versatility of AI enables researchers to integrate heterogeneous data sources, uncover novel applications of coumarins, and design more effective and targeted therapeutic agents. Despite existing challenges—including data quality, the need for experimental validation, and computational complexity—the integration of AI into coumarin research presents transformative opportunities for future medical innovations. This review summarizes recent advances, representative case studies, and prospective directions, emphasizing the importance of interdisciplinary collaboration to address current limitations. By combining the inherent therapeutic potential of natural phytochemicals with the computational power of AI, this field is advancing innovative strategies in drug development and expanding the frontiers of modern pharmacology.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1432 - 1452"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145522","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":"Induction of Oxidative Hormesis by TiO2 Nanoparticles Enhances Antibacterial Activity of Lactobacillus acidophilus","authors":"A. V. Lokteva,&nbsp;E. V. Trushlis,&nbsp;O. V. Ivankova,&nbsp;E. I. Koshel","doi":"10.1134/S1068162025602666","DOIUrl":"10.1134/S1068162025602666","url":null,"abstract":"<p><b>Objective:</b> The aim of this study was to investigate the potential induction of oxidative hormesis in probiotic <i>Lactobacillus acidophilus</i> by metal oxide nanoparticles. Special attention was given to the effect of different types of nanoparticles to trigger oxidative hormesis, influnce on bacteriocin synthesis and the antibacterial activity of the strain against antibiotic-resistant pathogens. <b>Methods:</b> This study employed sol-gel and precipitation methods to synthesize various metal oxide nanoparticles, which were characterized for their physicochemical properties and tested for their effects on <i>Lactobacillus acidophilus</i> growth. The interaction between TiO₂ nanoparticles and bacterial cells was analyzed using EDX and hydrogen peroxide assays, while gene expression related to oxidative stress and bacteriocin production was quantified by qRT-PCR, demonstrating enhanced antibacterial activity <i>via</i> oxidative hormesis. <b>Results and Discussion:</b> Research on the toxic effects of metal oxide nanoparticles (NPs) has primarily focused on their negative impact on bacterial growth and metabolism, which are well-documented. This study describes a positive influence of NPs despite predominant data about toxicity and confirms that TiO₂ NPs stimulate an increase of bacteriocin synthesis through oxidative hormesis induction. The described effect was reached by TiO₂ NPs at 15 μg/mL and resulted in a twofold increase in bacterial cell count. Oxidative hormesis induction was confirmed by enhanced gene expression associated with repair mechanisms and reactive oxygen species neutralization systems. Linkage of oxidative hormesis and antibacterial properties was shown by 8 bacteriocin genes expression increasing up to 6 times. This data determined the statistically significant increase in the inhibition zones of <i>E. coli</i> and <i>S. aureus</i> by 1.5 and 2.6 times, respectively. <b>Conclusions:</b> The obtained results provide a new approach to manipulating the antibacterial metabolism of <i>Lactobacillus</i> sp. for applications in both biotechnology and the development of biohybrid systems for personalized antibacterial therapy.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1801 - 1812"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145144824","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":"Cytotoxic Potential of Newly Synthesized 4-Aminoquinoline Hybrids on MDA-MB-231 Cells: Insights from Pharmacophore Modeling and Molecular Dynamics Simulation","authors":"A. A. Mattikopp,&nbsp;S. G. Alegaon,&nbsp;S. Gharge,&nbsp;S. D. Ranade,&nbsp;R. S. Kavalapure","doi":"10.1134/S1068162024606529","DOIUrl":"10.1134/S1068162024606529","url":null,"abstract":"<p><b>Objective:</b> This study aimed to design, synthesize, and evaluate novel 4-aminoquinoline hybrids as effective inhibitors of the <i>c</i>-Met kinase domain and assess their anti-proliferative activity against the MDA-MB-231 breast cancer cell line. <b>Methods:</b> The compounds were computationally designed and synthesized. Pharmacophore modeling was used to identify key structural features. Molecular docking studies were conducted to analyze interactions within the <i>c</i>-Met kinase binding pocket, and molecular dynamics simulations were performed to evaluate the stability and conformational behavior of the compounds. Density Functional Theory (DFT) computations further confirmed the optimized geometry of the hybrids. <b>Results and Discussion:</b> Two synthesized compounds exhibited notable inhibitory activity: compound (<b>VIb</b>), with a methoxy group at the 3rd position and a hydroxy group at the 4th position, achieved an IC₅₀ of 4.28 ± 1.05 µg/mL. Compound (<b>VIa</b>), containing a thiazole ring, also demonstrated significant activity. <b>Conclusions:</b> The study employed pharmacophore modeling to identify key structural features of the synthesized hybrids, which facilitated the understanding of their interactions with the <i>c</i>-Met kinase binding pocket through molecular docking studies. Furthermore, molecular dynamics simulations confirmed the stability and conformational behavior of the hybrids, and DFT computations supported their optimized geometries. This comprehensive approach highlights the potential of these novel hybrids as <i>c</i>-Met-targeting agents for cancer therapy.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1624 - 1644"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145389","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":"Comparison of Alternative Piperidine Deblocking Agents in the Solid-Phase Synthesis of Ingramon and Methylin","authors":"M. V. Klimova,&nbsp;A. S. Molokoedov,&nbsp;M. V. Ovchinnikov,&nbsp;M. E. Palkeeva,&nbsp;U. S. Kozhokar,&nbsp;D. V. Avdeev,&nbsp;M. V. Sidorova","doi":"10.1134/S1068162025602733","DOIUrl":"10.1134/S1068162025602733","url":null,"abstract":"<p><b>Objective:</b> The work is devoted to the comparison of alternative piperidine deblocking agents (4-methylpiperidine, piperazine, pyrrolidine) using the examples of solid-phase synthesis of ingramon, which has anti-inflammatory activity, and methylin, an agonist of the transmembrane APJ receptor. The possibility of using these peptides for the treatment of cardiovascular diseases dictates the need to develop optimized methods for their synthesis. <b>Methods:</b> The synthesis of ingramon and methylin was carried out by a solid-phase method using deblocking mixtures based on selected bases. The composition of the products obtained was assessed using analytical HPLC. The kinetics of Fmoc-protection cleavage was determined using spectrophotometry. <b>Results and Discussion:</b> In the synthesis of the aspartyl peptide ingramon, the lowest content of by-products was noted when using a mixture containing 10% piperazine for cleaving the Fmoc protection. In addition, piperazine is an accessible and low-toxic reagent, which is attractive for large-scale solid-phase peptide synthesis. In the synthesis of methylin, the maximum yield of the product was obtained using a deblocking mixture based on pyrrolidine. <b>Conclusions:</b> The selected deblocking reagents can successfully replace toxic piperidine in solid-phase peptide synthesis not only in the laboratory but also in the preparative scale. These reagents can find application in obtaining peptide pharmaceutical substances.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1725 - 1733"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145503","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":"Integration of Software for Nanotomography-Based 3D Tissue Reconstruction","authors":"D. О. Solovyevа,&nbsp;О. Y. Popadinets,&nbsp;I. S. Kolpashnikov,&nbsp;A. V. Altunina,&nbsp;V. A. Oleinikov","doi":"10.1134/S1068162024607146","DOIUrl":"10.1134/S1068162024607146","url":null,"abstract":"<p><b>Objective:</b> To enhance three-dimensional (3D) reconstruction of cellular tissues and their components at the nano scale by integrating dedicated software tools into optical probe nanotomography (OPNT). <b>Methods:</b> We incorporated the 3D Slicer open source platform into the OPNT workflow to standardize, optimize, and automate volumetric reconstruction. Atomic force microscopy (AFM) and optical microscopy datasets were imported into 3D Slicer, aligned, segmented, and rendered to generate high-resolution 3D models. A fragment of an astrocyte was used as a test sample to validate reconstruction accuracy and workflow efficiency. <b>Results and Discussion:</b> The enhanced OPNT pipeline produced reliable and reproducible 3D reconstructions of complex biological structures. Integration of 3D Slicer enabled precise registration of multimodal images and flexible segmentation tools, resulting in detailed morphology of astrocytic processes. Quantitative evaluation demonstrated improved spatial resolution and reduced user bias compared to manual reconstruction methods. The platform’s modularity facilitates adaptation to varied microscopy datasets and reconstruction tasks. <b>Conclusions:</b> The proposed methodology provides a robust, high-precision platform for 3D reconstruction of cellular and subcellular structures. It holds significant potential for specialized applications such as synaptic environment analysis of individual neurons and broad use in biomedical research and materials science.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1579 - 1585"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145554","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 Fully Substituted 1,2,3-Triazoles via Organocatalytic [3+2] Cycloaddition: Incorporation of Pyrazole and Imidazole Scaffolds as Potent EGFR-Targeted Anticancer Agents","authors":"Sreenivas Tumu,&nbsp;A. Samba Shiva Rao,&nbsp;Jagadeesh Kumar Ega","doi":"10.1134/S1068162024606633","DOIUrl":"10.1134/S1068162024606633","url":null,"abstract":"<p><b>Objective:</b> The present study aimed to synthesize novel imidazole- and pyrazole-containing 1,2,3-triazoles <i>via</i> organocatalytic [3+2] cycloaddition and to evaluate their anticancer activity against MCF-7, A-549, and HEK-293 cell lines. <b>Methods:</b> The synthesis began with <i>S</i>-alkylation of 1-methyl-1<i>H</i>-imidazole-2-thiol using 2-bromo-1-(4-chloro-1-methyl-1<i>H</i>-pyrazol-3-yl)ethan-1-one to yield 1-(4-chloro-1-methyl-1<i>H</i>-pyrazol-3-yl)-2-((1-methyl-1<i>H</i>-imidazol-2-yl)thio)ethan-1-one, followed by oxidation to form the key intermediate β-ketosulfone. Subsequent [3+2] cycloaddition between aryl azides and the α-ketosulfone led to the formation of fully substituted 1,2,3-triazoles. Anticancer activity of the synthesized compounds was assessed using the MTT assay. <i>In silico</i> molecular docking and ADMET analyses were also performed for the most active compounds. <b>Results and Discussion:</b> Structural confirmation of all synthesized compounds was achieved using ESI-MS, ¹H, and ¹³C NMR spectroscopy. Compound (<b>Vi</b>) exhibited the most potent cytotoxic activity against both MCF-7 and A-549 cancer cell lines, with IC₅₀ values of 4.18 ± 0.32 and 6.97 ± 0.41 μM, respectively. Compound (<b>Vg</b>) also demonstrated comparable activity, with IC₅₀ values of 4.42 ± 0.38 μM (MCF-7) and 7.53 ± 0.49 μM (A-549). These results were benchmarked against the standard drug Erlotinib. Further investigation of EGFR-inhibitory potential revealed that the most active compounds displayed strong binding affinity, with binding energies ranging from –7.98 to –9.63 kcal/mol, exceeding that of Erlotinib (–7.69 kcal/mol). <b>Conclusions:</b> A new series of fully substituted 1,2,3-triazoles was successfully synthesized and evaluated for their <i>in vitro</i> anticancer activity. Several compounds exhibited significant cytotoxicity against MCF-7 and A-549 cell lines while maintaining lower toxicity toward the non-cancerous HEK-293 cells. Compound (<b>Vi</b>), in particular, holds promise as a lead candidate for further development, given its potency and favorable <i>in silico</i> profile.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1700 - 1714"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145394","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":"Solid-Phase PCR on Film Biochips with Brush Polymer Cells, “Lab-On-A-Chip”","authors":"I. Yu. Shishkin,&nbsp;K. А. Sinnikov,&nbsp;G. F. Shtylev,&nbsp;R. A. Miftakhov,&nbsp;O. A. Zasedateleva,&nbsp;V. E. Kuznetsova,&nbsp;V. E. Shershov,&nbsp;S. A. Surzhikov,&nbsp;V. A.Vasiliskov,&nbsp;S. A. Lapa,&nbsp;A. V. Chudinov","doi":"10.1134/S1068162024607055","DOIUrl":"10.1134/S1068162024607055","url":null,"abstract":"<p><b>Objective:</b> To develop a multifactorial, highly sensitive nucleic acid analysis method on biological microarrays within an environmentally sealed system. This approach eliminates the need for transferring biological material between vessels and avoids adding components during the assay, thereby reducing contamination risk and enabling process automation. <b>Methods:</b> Polyethylene terephthalate (PET) film substrates for biochip fabrication were treated with corona discharge. A thin layer of photoactive polyvinyl acetate was deposited on the surface by spin coating. A matrix of cells composed of brush polymers was obtained through photoinitiated radical polymerization of monomers “from the surface” using photolithographic patterning under UV irradiation through a photomask. Reactive carboxyl groups on polymer chains were activated, and primers with C6-amino modification at the 5′-end were immobilized within biochip cells. PCR with extension of immobilized primers using Cy5-fluorescently labeled nucleotides was performed within the biochip cells. <b>Results and Discussion:</b> A method for nucleic acid analysis by solid-phase PCR with immobilized primer extension in a closed film biochip during thermocycling was successfully developed. Detection was achieved through endpoint digital fluorescence microscopy monitoring Cy5-fluorescently labeled nucleotide incorporation. The developed “film biochip” consists of PET film with an internal chamber, brush polymer cells containing immobilized primers, and channels for solution supply and removal. The biochip features low heat capacity and high thermal conductivity of thin-film components, thermocycling capability, and result detection by digital fluorescence microscopy through the lid and washing solution layer without biochip disassembly in an environmentally isolated lab-on-a-chip system. The method′s performance and functional suitability were demonstrated by analyzing samples containing DNA from pathogenic bacteria <i>Staphylococcus aureus</i> and <i>Legionella pneumophila</i>. <b>Conclusions:</b> Film biochips made of commercially available PET film with brush polymer cells show promise for further development and application in solid-phase PCR for multiplex nucleic acid analysis, lab-on-a-chip microanalysis technologies, and clinical laboratory applications.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1506 - 1520"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145501","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 Tetraesters of Indolyl-3-acetic Acid with 24-Epibrassinosteroids and Their Influence on the Initial Growth of Wheat Plants","authors":"R. P. Litvinovskaya,&nbsp;N. E. Manzhаlesаva,&nbsp;А. P. Savachka,&nbsp;A. L. Sauchuk,&nbsp;V. A. Khripach","doi":"10.1134/S1068162024607079","DOIUrl":"10.1134/S1068162024607079","url":null,"abstract":"<p><b>Objective:</b> The aim of this work was to synthesize 2,3,22,23-tetraindolyl-3-acetoxy derivatives of 24-epibrassinosteroids, study their growth-regulating activity at the initial stage of spring wheat development and influence on the content of endogenous brassinosteroids during the growth of wheat plants. It has been shown that brassinosteroid tetraesters of indolyl-3-acetic acid exhibit phytogrowth-regulating activity in the early stages of wheat plant growth. <b>Methods:</b> By treating 24-epibrassinosteroids with indolyl-3-acetic acid (IAA) anhydride in dioxane in the presence of DMAP, their 2,3,22,23-tetra-(3′-indolylacetoxy) derivatives were obtained. Quantitative analysis of endogenous BS content was performed by ELISA using previously developed test systems for the determination of 24-epibrassinosteroids, 28-homobrassinosteroids and brassinosteroids of the brassinolide group. <b>Results and Discussion:</b> The synthesized brassinosteroid tetraesters with IAA have a growth-stimulating effect at the initial stage of wheat plant development. Exogenous treatment of wheat plants with brassinosteroid solutions and their esters with IAA changes the brassinosteroid profile at the early stages of development. A decrease in the content of BS of the brassinolide group and 28-homobrassinosteroids 14 days after exogenous treatment confirms the fact that brassinosteroids participate in the processes of regulation of their biosynthesis, thus maintaining the steroid-hormonal balance for optimal growth and development of plants. <b>Conclusions:</b> For the first time, tetraesters of IAA and 24-epibrassinosteroids were synthesized. Primary screening of the obtained compounds in laboratory tests on wheat plants showed growth-stimulating concentration-dependent activity. Changes in the steroid-hormonal balance of BS in vegetative plants when treated with 24-epibrassinosteroids or BS tetraesters with IAA may indicate their participation in the processes of biosynthesis regulation. The obtained derivatives are promising for more in-depth study, primarily for investigating their effectiveness in field experiments.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1571 - 1578"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145521","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":"Olaparib Stimulates the Senescence of Ovarian Cancer Cells by Inhibiting SIRT1","authors":"Yanjun Wang,&nbsp;Xi Liu","doi":"10.1134/S1068162024606207","DOIUrl":"10.1134/S1068162024606207","url":null,"abstract":"<p><b>Objective:</b> The induction of cellular senescence in ovarian cancer cells has emerged as a promising therapeutic strategy. Olaparib, the first approved PARP inhibitor, is widely used in the treatment of various cancers, including ovarian cancer. This study aimed to investigate the effects of olaparib on the induction of senescence in ovarian cancer cells. <b>Methods:</b> A2780 ovarian cancer cells were treated with olaparib at concentrations of 15, 30, and 60 μM. DNA damage was assessed by measuring levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) and γH2AX. Cellular senescence was evaluated using senescence-associated β-galactosidase (SA-β-Gal) staining and telomerase activity assays. Gene and protein expression were analyzed by real-time PCR and Western blotting, respectively. <b>Results and Discussion:</b> Olaparib treatment led to a significant reduction in telomerase activity in A2780 cells. It also induced DNA damage, as evidenced by increased levels of 8-OHdG and γH2AX. Furthermore, olaparib promoted cellular senescence, confirmed by positive SA-β-Gal staining. Treatment with olaparib resulted in decreased expression of hTERT and Lamin B1, both of which are markers associated with cellular proliferation and nuclear integrity, respectively. Notably, olaparib downregulated the expression of SIRT1, a key regulator of cellular senescence, while upregulating acetylation of p53 at lysine 382 (ac-p53^K382) and p21 expression. Overexpression of SIRT1 attenuated olaparib-induced senescence in A2780 cells. <b>Conclusions:</b> These findings reveal a novel pharmacological activity and molecular mechanism of olaparib in promoting senescence in ovarian cancer cells through SIRT1 inhibition.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1547 - 1557"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145555","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":"Recent Developments in Structurally Diverse Anti-Tubercular Drug Molecules and Their Molecular Targets Against Mycobacterium tuberculosis","authors":"S. Alghamdi,&nbsp;N. F Qusty,&nbsp;A. Maulana,&nbsp;M. Ajmal,&nbsp;M. Khan,&nbsp;A. K. Mahato,&nbsp;S. Verma,&nbsp;M. Asif","doi":"10.1134/S1068162023603257","DOIUrl":"10.1134/S1068162023603257","url":null,"abstract":"<p><i>Mycobacterium tuberculosis</i> (<i>Mtb</i>), the primary etiological agent of tuberculosis (TB), remains a major global health threat. In recent years, <i>Mtb</i> strains exhibiting complete drug resistance have emerged, evolving unique mechanisms to survive within the host. Although multidrug therapy was introduced four decades ago, the rise of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains necessitates the urgent development of novel therapeutic targets and interventions. Current drug development efforts have been insufficient to curb the TB epidemic, with anti-TB drug discovery largely stagnant for nearly half a century. However, in the past decade, three promising drugs—delamanid, bedaquiline, and pretomanid—have unexpectedly emerged. Furthermore, numerous modified compounds, initially developed to combat other infections, have demonstrated potential anti-TB activity. These drugs exhibit diverse targets and mechanisms of action, including the inhibition of cell wall biosynthesis, DNA/RNA synthesis, protein synthesis, and metabolic pathways. This article reviews the molecular targets, mechanisms of action, drug interactions, and structure–activity relationships (SAR) of newly approved and repurposed drugs for TB treatment. While TB poses a global burden, its impact is disproportionately felt in developing countries, where latent <i>Mtb</i> infection is estimated to affect nearly one-third of the population. Although TB is curable, treatment becomes significantly more challenging with progression to MDR and even more so with XDR forms. Despite decades of stagnation, recent breakthroughs—including the discovery of delamanid and bedaquiline and the repurposing of drugs like linezolid and clofazimine—offer renewed hope for effective TB management.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1385 - 1431"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145144825","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}