Russian Journal of Bioorganic Chemistry最新文献

{"title":"Application of 3D Imaging in Biomedical Research","authors":"A. M. Safonov,&nbsp;A. V. Altunina,&nbsp;I. S. Kolpashnikov,&nbsp;D. O. Solovyeva,&nbsp;V. A. Oleynikov","doi":"10.1134/S1068162024607043","DOIUrl":"10.1134/S1068162024607043","url":null,"abstract":"<p>Three-dimensional microscopy (3D microscopy) has become an important tool in cellular analysis and biomedical research, providing unique opportunities to visualize and study complex biological structures. The capabilities of different types of microscopy in studying cellular structures and macromolecular complexes span a wide range of scales, from investigating cell behavior and function in physiological environments to understanding the molecular architecture of organelles. At each scale, the challenge of 3D imaging is to extract the highest possible spatial resolution while minimizing damage to living cells. This review highlights the various applications of 3D microscopy, including studying cancer, viruses, bacteria, and organ and implant microstructure analysis. In the context of oncology, 3D imaging allows detailed investigation of cellular interactions, tumor microenvironment, and tumor heterogeneity, which contributes to a better understanding of the mechanisms of metastasis and resistance to therapy. In virology, 3D methods help to reveal the structure of viruses and their interactions with cellular components, which is of key importance for the development of vaccines and antiviral drugs. Studying bacteria using 3D microscopy opens up new horizons in understanding colony formation, biodiversity, and pathogenicity. In addition, analyzing the microstructures of organs and implants using 3D technologies improves the quality and safety of medical devices. Finally, integrating 3D microscopy into the drug development process allows for more accurate assessment of the efficacy and toxicity of new compounds at the cellular level. Thus, 3D microscopy is a powerful tool for in-depth study of biological processes and the development of innovative solutions in medicine.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1453 - 1470"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145520","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":"Smart Delivery Systems of Sorafenib Based on Biopolymers and Supramolecular Assemblies","authors":"I. M. Le-Deygen,&nbsp;A. A. Skuredina,&nbsp;Van Cuong Bui,&nbsp;Minh Bao Ngoc Tran,&nbsp;Thi Lan Pham","doi":"10.1134/S1068162025600114","DOIUrl":"10.1134/S1068162025600114","url":null,"abstract":"<p>The challenge of effective antitumor therapy remains a pressing global issue, particularly when utilizing low-molecular-weight biologically active compounds. Sorafenib (SF), a proven treatment for kidney cancer, suffers from very low bioavailability, underscoring the critical need for innovative delivery systems. Enhancing its bioavailability could significantly expand sorafenib's therapeutic potential to other oncological diseases. Early strategies for sorafenib delivery involved liposomes, cyclodextrins, and polymeric micelles. However, over the past five years, there have been remarkable advancements in the design of more sophisticated supramolecular and “smart” delivery systems with improved biological performance. These advanced systems often incorporate biopolymers with tunable properties alongside synthetic bioorganic compounds, offering greater precision and efficacy. This review analyzes recent developments in sorafenib delivery systems, highlighting current progress and identifying potential directions for further innovation in this critical area of cancer therapy.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 3","pages":"1011 - 1021"},"PeriodicalIF":1.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145142273","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":"Design and Synthesis of Novel Imidazole-Bearing 1,2,3-Triazoles as Potent Anticancer Agents: Drug-Likeness, Pharmacophore, and Molecular Docking Exploration","authors":"B. V. Balaji,&nbsp;B. Hari Babu,&nbsp;G. Mahesh Kumar,&nbsp;B. Srinu,&nbsp;V. Pandu Ranga Rao,&nbsp;R. Surya Chandra Rao","doi":"10.1134/S1068162024603756","DOIUrl":"10.1134/S1068162024603756","url":null,"abstract":"<p><b>Objective:</b> A novel series of imidazole-based 1,2,3-triazole derivatives (<b>VIa–VIk</b>) was designed and synthesized as potential broad-spectrum anticancer agents. <b>Methods:</b> These compounds were obtained via a well-established copper(I)-catalyzed azide–alkyne cycloaddition (“click chemistry”), starting from (<i>E</i>)-2-butyl-4-chloro-1-methyl-1<i>H</i>-imidazole-5-carbaldehyde oxime. The structures of the synthesized compounds were confirmed using standard spectroscopic techniques, including infrared (IR), proton (¹H) and carbon (¹³C) nuclear magnetic resonance (NMR), and mass spectrometry (MS). <b>Results and Discussion:</b> The antiproliferative activities of the final compounds were evaluated against human lung adenocarcinoma (PC-9) and human colorectal carcinoma (HCT-116) cell lines, along with in vitro inhibitory assays targeting the epidermal growth factor receptor (EGFR). Compounds (<b>VId</b>) and (<b>VIh</b>) exhibited potent cytotoxic activity against the PC-9 cell line, with IC₅₀ values of 4.87 ± 0.4 and 3.74 ± 0.3 μM, respectively, surpassing the reference drug doxorubicin (IC₅₀ = 6.32 ± 0.3 μM). Molecular docking studies predicted that compounds (<b>VId</b>) and (<b>VIj</b>) bind favorably to the active site of EGFR, with IC₅₀ values of 0.76 and 0.25 μM, respectively. Docking results revealed that (<b>VId</b>) forms highly stable hydrogen bonds with amino acid residues Phe82, Met80, His18, and Gln42, which play key roles in ligand binding within the EGFR crystal structure associated with lung cancer mutations (PDB ID: 1M17). Furthermore, computational ADMET profiling was carried out using SwissADME and ADMETlab 2.0 to evaluate the pharmacokinetic properties and drug-likeness of the synthesized triazole compounds. <b>Conclusions:</b> In this study, a series of novel EGFR inhibitors incorporating 1,2,3-triazole scaffolds linked to oxime/imidazole moieties were successfully designed and synthesized.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 3","pages":"1034 - 1053"},"PeriodicalIF":1.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145142275","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":"Design, Synthesis, and Antimicrobial Study of Triad Hybrids of 1,2,3-Triazolo[4,5-b]pyridine: Click Chemistry and Azidation Using Hydrazine Hydrate","authors":"Heta B. Vasveliya,&nbsp;Jignesh H. Pandya,&nbsp;Hinaben K. Tilavat,&nbsp;Amita J. Jivani,&nbsp;Tanzil A. Juneja","doi":"10.1134/S1068162024606086","DOIUrl":"10.1134/S1068162024606086","url":null,"abstract":"<p><b>Objective:</b> The design and synthesis of new chemical entities (NCEs) with suitable physicochemical properties are crucial objectives in medicinal chemistry. This study focuses on the development of novel compounds with potential antimicrobial activity, employing a multi-step “click chemistry” strategy to synthesize ten diverse scaffolds derived from 3<i>H</i>-[1,2,3]triazolo[4,5-<i>b</i>]pyridin-3-ol. These compounds were designed to incorporate three distinct heterocyclic units within a single molecular framework. <b>Methods:</b> A novel azidation reagent—hydrazine hydrate in acetic acid—was employed for the efficient and environmentally benign synthesis of aryl azides. The resulting conjugates, 3-((1-(substituted phenyl)-1<i>H</i>-1,2,3-triazol-4-yl)methoxy)-3<i>H</i>-[1,2,3]triazolo[4,5-<i>b</i>]pyridines, were evaluated for antimicrobial activity against various microbial strains using minimum inhibitory concentration (MIC) assays. Additionally, molecular docking studies were conducted to assess the binding affinities of the synthesized compounds toward DNA gyrase (PDB ID: 4DUH). <b>Results and Discussion:</b> The synthesized conjugates exhibited varying degrees of antibacterial and antifungal activity <i>in vitro</i>. Among them, the scaffold bearing a trifluoromethyl (–CF₃) substituent on the aryl ring demonstrated the most potent antibacterial activity, with MIC values of 3.125 µg/mL against Bacillus subtilis and 6.75 µg/mL against <i>Escherichia coli</i>. In molecular docking simulations, the compound 3-((1-(2-(trifluoromethyl)phenyl)-1<i>H</i>-1,2,3-triazol-4-yl)methoxy)-3<i>H</i>-[1,2,3]triazolo[4,5-<i>b</i>]pyridine showed favorable binding energy (−7.6 kcal/mol), comparable to that of streptomycin (−7.5 kcal/mol), penicillin (−6.6 kcal/mol), and amphotericin B (−9.7 kcal/mol). <b>Conclusions:</b> The newly synthesized conjugates exhibit promising antibacterial and antifungal properties. In particular, the compound 3-((1-(2-(trifluoromethyl)phenyl)-1<i>H</i>-1,2,3-triazol-4-yl)methoxy)-3<i>H</i>-[1,2,3]triazolo[4,5-<i>b</i>]pyridine demonstrates potent antimicrobial activity and favorable binding interactions with DNA gyrase, suggesting its potential as a novel antimicrobial agent.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 3","pages":"1161 - 1170"},"PeriodicalIF":1.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145161242","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":"Combined Effects of Cytokine TRAIL-Based DR5-Specific Fusion Protein with Olaparib on Tumor Cell Lines with Different BRCA Mutation Status","authors":"A. V. Yagolovich,&nbsp;A. A. Isakova,&nbsp;E. V. Kukovyakina,&nbsp;D. A. Dolgikh,&nbsp;M. P. Kirpichnikov,&nbsp;M. E. Gasparian","doi":"10.1134/S1068162024606694","DOIUrl":"10.1134/S1068162024606694","url":null,"abstract":"<p><b>Objective:</b> Tumor cell death induction via activation of TRAIL (tumor necrosis factor-related apoptosis inducing ligand) cytokine signaling pathway is a promising strategy for anticancer therapy. Previously, we developed a fusion protein SRH-DR5-B-iRGD based on the DR5 (death receptor 5)-specific cytokine TRAIL variant DR5-B with antiangiogenic peptides. The SRH peptide specifically binds to the VEGFR2 (vascular endothelial growth factor receptor 2) receptor and blocks its VEGF-mediated activation; the iRGD peptide binds to integrin αvβ3 and the NRP-1 (neuropilin-1) receptor. All of these targets are known to be overexpressed on the surface of tumor cells. In the current study, we investigated the cytotoxic activity of the SRH-DR5-B-iRGD fusion protein in comparison with DR5-B <i>in vitro</i> in ovarian and breast adenocarcinoma cell lines with different <i>BRCA</i> mutation status in combination with olaparib, a targeted poly(ADP-ribose) polymerase (PARP) inhibitor. <b>Methods:</b> Target receptor expression and correlation analysis were performed using the online tool TNMplot. Recombinant proteins DR5-B and SRH-DR5-B-iRGD were obtained in <i>Escherichia coli</i>. Cell viability was studied by MTT assay. <b>Results and Discussion:</b> Olaparib synergistically enhanced cytotoxicity of TRAIL-based proteins regardless of the cells’ <i>BRCA</i> mutation status. Importantly, this effect was more pronounced for SRH-DR5-B-iRGD. <b>Conclusions:</b> The combination of SRH-DR5-B-iRGD with olaparib can be considered as a new approach for the treatment of ovarian and breast adenocarcinoma regardless of their <i>BRCA</i> mutation status.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 3","pages":"1128 - 1136"},"PeriodicalIF":1.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145161586","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":"Regulation of pou5f3 Family Pluripotency Gene Transcripts Stability by Ybx1 Ribonucleoprotein Complexes in Xenopus laevis Early Development","authors":"E. A. Parshina,&nbsp;A. G. Zaraisky,&nbsp;N. Y. Martynova","doi":"10.1134/S1068162025602265","DOIUrl":"10.1134/S1068162025602265","url":null,"abstract":"<p><b>Objective:</b> Stability regulation of <i>pou5f3</i> family transcripts by association with Ybx1, the ribonucleoprotein complex factor, was studied. It is known that the clawed frog Xenopus laevis has three genes belonging to the POU5 family: <i>pou5f3.1/oct91, pou5f3.2/oct25</i>, and <i>pou5f3.3/oct60</i>. The Pou5f3 family factors are orthologs of the mammalian embryonic stem cell OCT4 pluripotency factor. However, the expression patterns of these genes differ over time<i>. Pou5f3.3/oct60</i> transcripts are stored in oocytes, are present in large quantities in fertilized eggs, and then degrade only after fertilization. <i>Pou5f3.2/oct25</i> transcripts are also present in the zygote, but their numbers increase even more during the development process. Finally, <i>pou5f3.1/oct91</i> transcription begins only after the activation of the embryo genome at the middle blastula stage. <b>Methods:</b> To study the effect of Ybx1 on the mRNA stability of the POU5 family, we used the Ybx1 gain/loss of function assay and RIP (riboimmunoprecipitation) of myc-tagged Ybx1 complexes. <b>Results and Discussion:</b> In the present work, we revealed a much higher specificity of the Ybx1 factor to form a complex with the maternal mRNA of the pou5f3.3/oct60 gene compared to zygotic mRNAs of pou5f3.1/oct91 and pou5f3.2/oct25. <b>Conclusions:</b> Since Ybx1 is a protein that, on the one hand, is involved in the interaction with cytoskeletal proteins, and, on the other hand, binds and stabilizes pluripotency-associated transcripts, it can play a linking role in between the degradation of these maternal transcripts and cytoskeletal rearrangements during the onset of morphogenetic cell movements during the formation of germ layers.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 3","pages":"1297 - 1305"},"PeriodicalIF":1.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145161445","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":"Sequence Specificity of Dimeric Bisbenzimidazoles for DNA AT Sequences of Different Nucleotide Compositions, as Determined by Footprinting","authors":"D. S. Naberezhnov,&nbsp;А. F. Arutuynyan,&nbsp;А. D. Beniaminov,&nbsp;N. М. Smirnov,&nbsp;D. N. Kaluzhnyi,&nbsp;A. L. Zhuze,&nbsp;O. Y. Susova","doi":"10.1134/S1068162024606700","DOIUrl":"10.1134/S1068162024606700","url":null,"abstract":"<p><b>Objective:</b> The study aimed to investigate the site-specificity of binding to DNA of three series of minor groove ligands – dimeric bisbenzimidazoles DB₂(<i>n</i>), DB₂P(<i>n</i>), and DB₂Py(<i>n</i>) – using DNAase I footprinting. The compounds consist of two bisbenzimidazole units linked by oligomethylene linkers of varying lengths (<i>n</i>), with structural modifications to enhance DNA-binding properties. <b>Methods:</b> The binding specificity of the compounds was determined using DNAase I footprinting. The DB₂(<i>n</i>) and DB₂P(<i>n</i>) series are analogs of Hoechst 33342, modified by removing hydrophobic ethoxyphenol cores and introducing hydrophilic aminomethylene groups. The DB₂Py(<i>n</i>) series incorporates a pyrrolcarboxamide group, a structural unit of the AT-specific antibiotic netropsin. The interaction of these compounds with DNA sequences was analyzed to identify their binding preferences. <b>Results and Discussion:</b> All studied compounds demonstrated specificity for AT-rich DNA sequences. The DB₂P(<i>n</i>) and DB₂(<i>n</i>) series exhibited increased affinity for (AATT)₃ and TTTT sequences. The DB₂Py(<i>n</i>) series showed high specificity to AT-rich regions, with a preference for the TTTT motif. None of the compounds interacted with sequences containing fewer than four AT base pairs. These findings highlight the influence of structural modifications on DNA-binding specificity and affinity. <b>Conclusions:</b> The study revealed that dimeric bisbenzimidazoles DB₂(<i>n</i>), DB₂P(<i>n</i>), and DB₂Py(<i>n</i>) exhibit distinct binding preferences for AT-rich DNA sequences, with DB₂Py(<i>n</i>) showing a pronounced affinity for the TTTT motif. The results demonstrate the potential of these compounds as tools for targeting specific DNA sequences, with implications for molecular biology and drug design.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 3","pages":"1137 - 1146"},"PeriodicalIF":1.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145161329","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":"Environmentally Friendly Synthesis of Coumarin–Pyrazolo[1,5-a]pyrimidine Hybrids with Potent Antibacterial and Antibiofilm Activities","authors":"T. R. A. Sangma,&nbsp;L. B. Marpna,&nbsp;M. Rymbai,&nbsp;S. Kaping,&nbsp;V. V. Borah,&nbsp;J. N. Vishwakarma","doi":"10.1134/S1068162024606360","DOIUrl":"10.1134/S1068162024606360","url":null,"abstract":"<p><b>Objective:</b> This study aimed to synthesize a series of coumarin–pyrazolo[1,5-<i>a</i>]pyrimidine hybrid compounds and evaluate their potential antibacterial and antibiofilm activities. <b>Methods:</b> In our synthetic approach, a mixture of 3-acetylcoumarin (<b>I</b>) and <i>N</i>,<i>N</i>-dimethylformamide dimethyl acetal (DMF-DMA) was refluxed in toluene to afford the enaminone intermediate (<b>II</b>). Subsequent condensation with 3-aminopyrazoles in the presence of potassium hydrogen sulfate (KHSO₄) yielded a series of 7-(2-oxo-2<i>H</i>-chromen-3-yl)pyrazolo[1,5-<i>a</i>]pyrimidine derivatives. The structures of the synthesized compounds were confirmed using spectroscopic and analytical techniques, including FT-IR, ¹H, ¹³C NMR, and high-resolution mass spectrometry (HRMS). Antibacterial and antibiofilm activities were evaluated against <i>Staphylococcus epidermidis</i> ATCC 35984 and <i>Pseudomonas aeruginosa</i> using MIC, MIC₅₀ assays, and biofilm formation inhibition studies. <b>Results and Discussion:</b> The synthesized coumarin–pyrazolo[1,5-<i>a</i>]pyrimidine (CPP) hybrids (<b>IVa–IVj</b>) were obtained in high yields (74–92%) within short reaction times (9–18 min). These compounds exhibited significant anti-adhesion and antibiofilm activities against both <i>S. epidermidis</i> and <i>P. aeruginosa</i>. All compounds were tested for their ability to inhibit bacterial cell adhesion to polystyrene surfaces. <b>Conclusions:</b> Hybrids (<b>IVd</b>) and (<b>IVe</b>) demonstrated outstanding and consistent antibiofilm activity against strong biofilm-forming strains, <i>S. epidermidis</i> ATCC 35984 and <i>P. aeruginosa</i>, indicating broad-spectrum efficacy at low concentrations.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 3","pages":"1306 - 1319"},"PeriodicalIF":1.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145161245","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":"Evaluation of Natural Monoterpene Indole Alkaloids as Potent Fungicide Candidates","authors":"Zhuoyi Wang,&nbsp;Yanyan Chen,&nbsp;Hean Liu,&nbsp;Yueming Li,&nbsp;Mingjie Zhang,&nbsp;Yongyong Zhang,&nbsp;Junwei Sun","doi":"10.1134/S1068162025600709","DOIUrl":"10.1134/S1068162025600709","url":null,"abstract":"<p><b>Objective:</b> The fungicidal activity of 86 monoterpene indole alkaloids (MIAs) derived from plants was evaluated to identify novel lead compounds with antifungal potential. <b>Methods:</b> In this study, both <i>in vitro</i> and <i>in vivo</i> antifungal assays were performed to assess the efficacy of the selected MIAs. <b>Results and Discussion:</b> Among the tested compounds, rhazinilam (<b>32</b>) and rhazinal (<b>33</b>) exhibited markedly stronger antifungal activity against <i>Aspergillus niger</i> than ketoconazole in preliminary screenings. Further evaluation using mycelial growth inhibition assays confirmed that both compounds were significantly more active than ketoconazole against <i>A. niger</i>, <i>B. dothidea</i>, and <i>F. oxysporum</i> f. sp. <i>cubense in vitro</i>. The IC₅₀ values for rhazinilam (<b>32</b>) were &lt; 5, &lt; 10, and 17.89 μg/mL, respectively; for rhazinal (<b>33</b>), the values were &lt; 2.5, &lt; 5, and &lt; 5 μg/mL, respectively. Moreover, <i>in vivo</i> tests on cucumber leaves demonstrated that at a concentration of 40 μg/mL, compounds (<b>32</b>) and (<b>33</b>) provided significant protection against <i>A. niger</i>, with protection rates of 77.27 and 100%, respectively, compared to 47.62% for ketoconazole. <b>Conclusions:</b> Rhazinilam (<b>32</b>) and rhazinal (<b>33</b>) demonstrated potent antifungal activity in both <i>in vitro</i> and <i>in vivo</i> experiments, highlighting their promise as lead candidates for the development of novel fungicidal agents.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 3","pages":"1339 - 1345"},"PeriodicalIF":1.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145161246","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":"Design, Synthesis, and Evaluation of Antitumor Activity of Novel Pyrimidine Derivatives Containing Acrylamide and a Cyano Group","authors":"Hongjing Chen,&nbsp;Dongling Gu,&nbsp;Jiahui Han,&nbsp;Zichen Yang,&nbsp;Shihao Wang,&nbsp;Lingling Chi,&nbsp;Fuqiang Yu,&nbsp;Hao Wang,&nbsp;Hongmin Liu,&nbsp;Yu Ke,&nbsp;Qiurong Zhang","doi":"10.1134/S1068162024605019","DOIUrl":"10.1134/S1068162024605019","url":null,"abstract":"<p><b>Objective:</b> Based on the observed in vitro antitumor activity, the conformational influence of various substituents at the 2-position of the pyrimidine ring was systematically investigated to develop more effective antitumor pyrimidine analogs. <b>Methods:</b> A series of novel pyrimidine derivatives containing acrylamide and cyano groups were designed and synthesized. Their antiproliferative activities against four human tumor cell lines (MDA-MB-231, MGC-803, PC-3, and A549) were evaluated using the MTT assay. Additionally, colony formation, migration, cell cycle distribution, and apoptosis assays were performed to elucidate the antitumor mechanisms of compound (<b>XVIIIg</b>). <b>Results and Discussion:</b> Compound (<b>XVIIIg</b>) exhibited the strongest inhibitory activity against PC-3 cells, with an IC₅₀ value of 1.50 ± 0.29 μM. Cellular assays confirmed that (<b>XVIIIg</b>) significantly suppressed PC-3 cell proliferation and migration, induced G₀/G₁ cell cycle arrest, and promoted apoptosis. Structural modifications at the 2-position of the pyrimidine ring had a pronounced effect on <i>in vitro</i> antitumor activity. The 4-fluorophenyl (4-F-C₆H₄) substituent in compound (<b>XVIIIg</b>) contributed to its superior inhibitory effect, suggesting its potential as a lead compound. <b>Conclusions:</b> Among the 21 synthesized compounds, (<b>XVIIIg</b>) demonstrated the most potent antiproliferative and antimigratory activity, along with dose-dependent apoptosis induction in PC-3 cells. These results highlight its promise as a candidate for further development of novel antitumor agents.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 3","pages":"1054 - 1069"},"PeriodicalIF":1.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145141943","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}