Russian Journal of Bioorganic Chemistry最新文献

{"title":"Comparison of DNA Analysis on Biochips with Brush Polymer Cells and Cross-Linked Polymer Cells","authors":"R. A. Miftakhov,&nbsp;G. F. Shtylev,&nbsp;I. Yu. Shishkin,&nbsp;V. E. Shershov,&nbsp;V. E. Kuznetsova,&nbsp;S. A. Surzhikov,&nbsp;V. A. Vasiliskov,&nbsp;O. A. Zasedateleva,&nbsp;A. Yu. Ikonnikova,&nbsp;T. V. Nasedkina,&nbsp;A. V. Chudinov","doi":"10.1134/S106816202460692X","DOIUrl":"10.1134/S106816202460692X","url":null,"abstract":"<p><b>Objective:</b> The regulation of substrate surface properties in biochip technology opens the possibility of optimizing platforms for efficient biomolecule recognition. The research aims to explore the potential of using brush polymers to improve the sensitivity and speed of DNA analysis on biochips. <b>Methods:</b> Brush polymer cells for biochips were prepared by UV-initiated polymerization of monomers from the surface on polyethylene terephthalate substrates. Cross-linked hydrogel polymer cells for biochips were prepared on polybutylene terephthalate substrates by copolymerization of gel components with DNA probes. The probes in brush polymer cells were immobilized through activated carboxyl groups. A 124 nucleotides long DNA target corresponding to the 7th exon of the human ABO gene was used for hybridization analysis. Hybridization of the target DNA was studied on biochips with cells made of brush polymers and cross-linked polyacrylamide hydrogels. The results were evaluated by digital fluorescence microscopy. <b>Results and Discussion:</b> Higher intensity of fluorescence signals and higher ratio of signals of cells with perfect duplexes to those of cells with imperfect duplexes were observed in cells made of brush polymers compared to cells made of three-dimensional cross-linked polymers. Achievement of hybridization signal up to 90% of saturation occurred at the same time in both cell types. <b>Conclusions:</b> Hybridization analysis on brush polymer cells in biochip technology showed increased sensitivity in detecting single nucleotide mutations.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 3","pages":"1255 - 1261"},"PeriodicalIF":1.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145161581","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, Spectral Characteristics, and Tumor Imaging of a Fluorescent Small-Molecule Probe Containing Selenium Indole Sulfonate","authors":"M. Liu,&nbsp;Z. Wang,&nbsp;F. Jin","doi":"10.1134/S1068162024606153","DOIUrl":"10.1134/S1068162024606153","url":null,"abstract":"<p>–<b>Objective:</b> Selenium-containing indole derivatives are widely utilized in biomarker research due to their high fluorescence efficiency, water solubility, and selectivity. However, strategies to enhance their fluorescence stability and biocompatibility remain underdeveloped. <b>Methods:</b> To improve the water solubility and biocompatibility of selenium–indole (Se-In)-based fluorescent small molecules, a sulfonate group was introduced as a hydrophilic moiety. <b>Results and Discussion:</b> A selenium-conjugated molecule was designed to address the issue of fluorescence instability. The optical and physicochemical properties of the resulting probe were evaluated using fluorescence and UV–Vis spectroscopy. The probe exhibited a maximum emission wavelength between 550 and 560 nm and a maximum absorption wavelength at 600 nm. The probe demonstrated favorable spectral properties. Cell imaging experiments confirmed the good biocompatibility of the fluorescent probe with tumor cells across multiple detection channels. This study successfully synthesized Se-In fluorescent small molecules with enhanced fluorescence stability and biocompatibility. <b>Conclusions:</b> The developed probe provides a novel approach for future exploration of selenium-containing indole-based fluorescent molecules.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 3","pages":"1224 - 1232"},"PeriodicalIF":1.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145161582","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 Senexin B and Antitumor Agents on Neuroblastoma and Glioblastoma Cell Lines","authors":"D. V. Mazur,&nbsp;S. S. Pogodaeva,&nbsp;O. A. Kuchur,&nbsp;O. O. Miletina,&nbsp;A. I. Rezekina,&nbsp;E. G. Petrosyan,&nbsp;D. A. Rudik,&nbsp;E. I. Ivanova,&nbsp;A. A. Shtil,&nbsp;N. V. Antipova","doi":"10.1134/S1068162024607080","DOIUrl":"10.1134/S1068162024607080","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Objective:&lt;/b&gt; Neurogenic tumors are highly heterogeneous, causing difficulties in finding a universal therapeutic target. In glioblastoma and neuroblastoma, MYCN oncogene copy-number disruption, gene transcription disruption and overall high transcriptional deregulation are found. We analyzed changes in cell survival and changes in expression of &lt;i&gt;MYCN&lt;/i&gt;, &lt;i&gt;HAND2&lt;/i&gt;, &lt;i&gt;PHOX2A&lt;/i&gt;, &lt;i&gt;PHOX2B&lt;/i&gt; oncogenes after exposure to senexin B in combination with the potential therapeutic agent 10058-F4 and temozolomide. &lt;b&gt;Methods:&lt;/b&gt; Resazurin assay and MTT assay, as well as real-time PCR were used. &lt;b&gt;Results and Discussion:&lt;/b&gt; Glioblastoma did not respond with a change in viability after incubation with 10058-F4, growth of one cell line of neuroblastoma was suppressed. One glioblastoma cell line was resistant to the tested concentrations of temozolomide, with the maximum inhibitory effect on the other cell line starting at 250 μM. Neuroblastoma did not respond with decreased survival following exposure to temozolomide. In the Kelly neuroblastoma line, we observed &lt;i&gt;PHOX2B&lt;/i&gt; activation and decreased &lt;i&gt;PHOX2A&lt;/i&gt; expression after drug exposure. Incubation of cells with 10058-F4 was accompanied by a significant decrease in &lt;i&gt;MYCN&lt;/i&gt; mRNA levels. In the IMR-32 line, &lt;i&gt;MYCN&lt;/i&gt; expression was reduced only upon simultaneous exposure to senexin B and 10058-F4. Co-incubation of temazolomide and senexin B resulted in the significant activation of all genes examined except &lt;i&gt;PHOX2A&lt;/i&gt;. In the glioblastoma cell line T98G, only the basal level of &lt;i&gt;PHOX2A&lt;/i&gt; mRNA was detected, which fell after exposure to all combinations tested. Meanwhile, the expression of other genes increased from exposure. &lt;i&gt;MYCN&lt;/i&gt; and &lt;i&gt;PHOX2A&lt;/i&gt; transcripts were detected in the U87MG cell line. Compound 10058-F4 decreased the expression of both genes and increased &lt;i&gt;PHOX2B&lt;/i&gt; expression. Other combinations of substances also decreased &lt;i&gt;MYCN&lt;/i&gt; and &lt;i&gt;PHOX2A&lt;/i&gt; expression. The Kelly line responded with a statistically significant decrease in survival after incubation with senexin B in combination with 10058-F4, but less than after 10058-F4 alone. There was no cytotoxic effect for the IMR-32 cell line, but we observed increased cell survival after incubation with temazolomide and its combination with senexin B. In glioblastoma cell lines, we observed decreased cell survival after exposure to senexin B and 10058-F4. In the U87MG cell line, viability was decreased by 25–35% after incubation with temozolomide, as well as with the combination of senexin B and temozolomide. &lt;b&gt;Conclusions:&lt;/b&gt; Our work shows the substance 10058-F4 is not effective against glioblastoma. In neuroblastoma cell lines, &lt;i&gt;PHOX2B&lt;/i&gt; and &lt;i&gt;MYCN&lt;/i&gt; respond most strongly to changes in expression; in glioblastoma cell lines, it is difficult to detect unambiguous changes in gene expression, except for a decrease in &lt;i&gt;PHOX2A&lt;/i&gt; (also &lt;i&gt;MYCN&lt;/i&gt; for U87MG) in both cell lines after any d","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 3","pages":"1279 - 1286"},"PeriodicalIF":1.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145161589","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 and Anticancer Activity of Diethyl (((5-(substituted phenyl)-1,3,4-thiadiazol-2-yl)amino)(quinolin-2-yl)methyl)phosphonate","authors":"Shailee V. Tiwari,&nbsp;Mahavir H. Ghante,&nbsp;Dattatraya N. Pansare,&nbsp;Nileema S. Gore,&nbsp;Rohini N. Shelke,&nbsp;Shashikant V. Bhandari","doi":"10.1134/S1068162024605998","DOIUrl":"10.1134/S1068162024605998","url":null,"abstract":"<p><b>Objective:</b> This study reports the efficient catalysis of a three-component reaction involving 5-(substituted phenyl)-1,3,4-thiadiazol-2-amine (<b>IIIa–IIIq</b>), quinoline-2-carbaldehyde, and triethyl phosphite, using zirconium oxychloride (ZrOCl₂) as a catalyst in ethanol under reflux conditions. The reaction yields α-aminophosphonates in good to excellent yields. Notably, the catalyst can be recovered and reused multiple times without significant loss of activity. <b>Methods:</b> A series of diethyl (((5-(substituted phenyl)-1,3,4-thiadiazol-2-yl)amino)(quinolin-2-yl)methyl)phosphonate derivatives (<b>VIa–VIq</b>) was synthesized and evaluated for <i>in vitro</i> anticancer activity against the HCC827 and H1975 human non-small cell lung cancer cell lines using the MTT assay. <b>Results and Discussion:</b> The structure–activity relationship (SAR) analysis revealed that electron-withdrawing groups on the phenyl ring enhance anticancer activity, while electron-donating groups, the presence of an alkyl chain between the thiadiazole and phenyl rings, and increased steric bulk on the phenyl ring are detrimental to activity. Additionally, due to their low selectivity towards wild-type EGFR (WT-EGFR), the synthesized compounds may exhibit reduced toxicity associated with WT-EGFR inhibition. Compounds (<b>VIe</b>) and (<b>VIf</b>) showed selective cytotoxicity toward cancer cells and did not display toxicity against normal cells at concentrations up to IC₅₀ &gt;20 μM. <b>Conclusions:</b> These findings provide valuable leads that merit further optimization for the development of improved cancer therapeutics.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 3","pages":"1115 - 1127"},"PeriodicalIF":1.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145161393","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 Quinoline–Bearing Dihydropyridine Hybrids on A549 Lung Cancer Cells","authors":"V. Kuthe,&nbsp;S. G. Alegaon,&nbsp;R. S. Kavalapure,&nbsp;S. Gharge,&nbsp;S. D. Ranade","doi":"10.1134/S1068162024606827","DOIUrl":"10.1134/S1068162024606827","url":null,"abstract":"<p><b>Objective:</b> This study aimed to design, synthesize, and evaluate novel quinoline–dihydropyridine hybrids as potential inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR-TK), assessing their antiproliferative activity against the human lung cancer cell line A549. <b>Methods:</b> The compounds were designed <i>in silico</i> and synthesized. Molecular docking studies were performed to assess their binding affinities within the EGFR-TK active site. Molecular dynamics (MD) simulations were conducted to investigate the stability and conformational dynamics of the ligand–protein complexes. Additionally, density functional theory (DFT) calculations were used to optimize the molecular geometry of the hybrids and confirm their electronic properties. <b>Results and Discussion:</b> Among the synthesized compounds, two demonstrated notable EGFR-TK inhibitory activity: compound (<b>VIc</b>), bearing a methoxy substituent at the 4-position, exhibited an IC₅₀ of 1.455 ± 1.17 µg/mL, while compound (<b>VIh</b>), containing a hydroxy group at the same position, showed an IC₅₀ of 1.736 ± 1.24 µg/mL. For comparison, the reference drug erlotinib exhibited an IC₅₀ of 7.32 ± 0.52 µg/mL. Molecular modeling identified structural determinants responsible for the observed activity, including favorable hydrogen bonding and hydrophobic interactions within the EGFR-TK active site. <b>Conclusions:</b> This integrated experimental and computational study underscores the potential of quinoline–dihydropyridine hybrids as promising EGFR-TK inhibitors. The findings provide a structural basis for further optimization of these compounds as candidates for targeted lung cancer therapy.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 3","pages":"1365 - 1384"},"PeriodicalIF":1.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145161588","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":"Search for Possible Conjugation Sites of Electrophiles with Biomolecules by Molecular Modeling","authors":"D. A. Belinskaia,&nbsp;E. I. Savelieva","doi":"10.1134/S1068162025601211","DOIUrl":"10.1134/S1068162025601211","url":null,"abstract":"<p><b>Objective:</b> The ability for rapid adduct formation with nucleophilic groups of proteins, nucleic acids, and lipids is among the main factors responsible for the toxic effects of electrophiles. Considering that the number of toxic electrophiles is practically unlimited, and they can form adducts with many molecular targets, a purely empirical approach to characterizing the adductome is obviously unproductive. The aim of this study was to develop a method for primary <i>in silico</i> assessment of the probability of conjugation of electrophiles with a particular modification site. <b>Methods:</b> For the model group of electrophiles, quantum-chemical indices were obtained by DFT calculations. The interaction of the electrophiles with potential sites of their covalent binding with plasma proteins was investigated with the help of molecular docking. <b>Results and Discussion:</b> The resulting data were used to compile a scale for assessing the hardness of electrophiles. The priority sites for covalent binding of the electrophiles to plasma proteins were determined. <b>Conclusions:</b> An algorithm for the computer selection of possible conjugation sites of electrophiles with biological macromolecules was developed.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 3","pages":"1320 - 1338"},"PeriodicalIF":1.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145161565","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":"Effect of Different Coatings on Immobilization of Biomolecules in Brush Polymer Cells","authors":"G. F. Shtylev,&nbsp;I. Yu. Shishkin,&nbsp;R. A. Miftakhov,&nbsp;S. A. Polyakov,&nbsp;V. E. Shershov,&nbsp;V. E. Kuznetsova,&nbsp;S. A. Surzhikov,&nbsp;V. I. Butvilovskaya,&nbsp;V. E. Barsky,&nbsp;V. A. Vasiliskov,&nbsp;O. A. Zasedateleva,&nbsp;A. V. Chudinov","doi":"10.1134/S1068162024606864","DOIUrl":"10.1134/S1068162024606864","url":null,"abstract":"<p><b>Objective:</b> Biochips with protein and oligonucleotide probes are used in the analysis of samples containing target proteins and nucleic acids. The selection of materials for biochip substrates and the functionalization of the carrier surface are among the key challenges of biochip technology that affect the sensitivity of the assay. <b>Methods:</b> Black polybutylene terephthalate substrates for biochip fabrication were modified by coating them with photoactive polymers: poly(ethylene-co-propylene-co-5-methylene-2-norbornene), acetylcellulose, polyvinyl acetate, and polyvinyl butyral. The polymer coatings were applied by centrifugation followed by drying. The effect of polymer coating on biochip characteristics was investigated. A matrix of hydrophilic cells made of brush polymers with functional epoxy groups, in which DNA probes and human immunoglobulins were immobilized, was obtained by the method of photoinitiated radical polymerization on substrates. The functionality of probes was investigated by hybridization analysis and reaction with specific antibodies. The binding efficiency of probes to molecular targets was evaluated on biochips with different polymer coatings. <b>Results and Discussion:</b> Cells from brush polymers obtained on substrates from polybutylene terephthalate coated with thin films of poly(ethylene-co-propylene-co-5-methylene-2-norbornene), acetylcellulose, polyvinyl acetate and polyvinyl butyral, firmly adhere to the substrate surface, do not break and do not peel off under conditions of DNA hybridization analysis and immunochemical analysis of proteins. The polymer coatings adsorbed insignificantly the analyzed molecular targets, so the result was observed high contrast of fluorescence image of cells after binding of fluorescently labeled molecular targets with molecular probes immobilized in biochip cells. <b>Conclusions:</b> Biochips prepared on polybutylene terephthalate substrates coated with polyvinyl butyral and poly(ethylene-co-propylene-co-5-methylene-2-norbornene) showed the best binding efficiency of immobilized molecular DNA probes and immunoglobulins to responsive molecular targets compared to polyvinyl acetate and acetyl cellulose coatings and are promising for lab-on-a-chip microanalysis technology.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 3","pages":"1206 - 1217"},"PeriodicalIF":1.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145161587","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":"A Novel Piperine Derivative, NOHJ, Exerts Antibreast Cancer Effects by Inhibiting MDM2","authors":"Xing Liu,&nbsp;Jingliang He,&nbsp;Wenhao Cheng,&nbsp;Xiaoshuo Wang,&nbsp;Meiqi Zhang,&nbsp;Sen Wang,&nbsp;Lu Chen,&nbsp;Siyi Zhang,&nbsp;Chongyun Zhou,&nbsp;Lili Zhou,&nbsp;Boyu Zhang,&nbsp;Dan Wang,&nbsp;Yizhuo Song,&nbsp;Xiujun Wang,&nbsp;Jing Ji","doi":"10.1134/S1068162024605718","DOIUrl":"10.1134/S1068162024605718","url":null,"abstract":"<p><b>Objective:</b> To design and synthesize a novel piperine derivative with enhanced antitumor efficacy compared to the natural compound piperine. <b>Methods:</b> Compound NOHJ was synthesized via the condensation of (<i>E</i>)-3-(4,5-dimethoxy-2-nitrophenyl)acrylic acid with 4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline. Its antitumor activity was evaluated using both <i>in vitro</i> and <i>in vivo</i> models. Potential molecular targets of NOHJ were identified through molecular docking, Western blotting, and immunofluorescence assays. <b>Results and Discussion:</b> NOHJ exhibited significant antitumor activity and demonstrated greater efficacy than piperine in inhibiting cell adhesion, migration, invasion, and colony formation in MDA-MB-231 and MCF-7 breast cancer cell lines. Additionally, NOHJ effectively suppressed tumor growth <i>in vivo</i> and inhibited angiogenesis in the chick embryo chorioallantoic membrane (CAM) assay. Mechanistic studies revealed that NOHJ treatment upregulated the expression of p53 and p21, while downregulating CDK1 and CCNB1, indicating cell cycle disruption. <b>Conclusions:</b> NOHJ exerts its antibreast cancer effects by targeting and inhibiting MDM2, stabilizing p53, and modulating key regulators of the cell cycle, ultimately leading to G₂/M phase arrest and apoptosis. These findings suggest that NOHJ is a promising therapeutic candidate for breast cancer.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 3","pages":"1070 - 1082"},"PeriodicalIF":1.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145141995","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 Novel N-Alkyl-3-mesityl-5-methyl-4,5-dihydro-isoxazole-5-carboxamide Molecules: In Vitro Antimicrobial, Antimalarial Evaluation, and In Silico Prediction Studies","authors":"Amit Chouhan,&nbsp;Sumit Kumar,&nbsp;Ajit Joshi,&nbsp;Satyanarayana Battula","doi":"10.1134/S106816202460627X","DOIUrl":"10.1134/S106816202460627X","url":null,"abstract":"<p><b>Objective:</b> This study reports the synthesis and characterization of a series of novel <i>N</i>-alkyl-substituted 3-mesityl-5-methyl-4,5-dihydroisoxazole-5-carboxamide derivatives (<b>VIa–VI6j</b>). <b>Methods:</b> The compounds were structurally confirmed by ¹H NMR and LC-MS analyses. Their <i>in vitro</i> antimicrobial activities were evaluated against two Gram-positive bacteria (<i>Streptococcus pyogenes</i> and <i>Staphylococcus aureus</i>), two Gram-negative bacteria (<i>Pseudomonas aeruginosa</i> and <i>Escherichia coli</i>), and three fungal strains (<i>Candida albicans</i>, <i>Aspergillus niger</i>, and <i>Aspergillus clavatus</i>). Additionally, the antimalarial activity was assessed against <i>Plasmodium falciparum</i>. <b>Results and Discussion:</b> Several compounds, including (<b>VIa</b>), (<b>VIb</b>), (<b>VId</b>), (<b>VIe</b>), and (<b>VIg</b>), exhibited superior potency compared to standard reference drugs. Others, such as (<b>VIc</b>), (<b>VIf</b>), (<b>VIi</b>), and (<b>VIj</b>), demonstrated moderate to comparable activity (~50% relative potency). Molecular docking studies provided insights into the potential binding interactions of these isoxazoline carboxamide derivatives, supporting their observed biological activity. Furthermore, density functional theory (DFT) calculations and ADMET predictions reinforced the pharmacological potential of these molecules. <b>Conclusions:</b> among the evaluated compounds, compound (<b>VId</b>) exhibited the most pronounced biological activity, characterized by significant antibacterial and potent antimalarial effects. Compounds (<b>VIa</b>), (<b>VIb</b>), (<b>VIh</b>), and (<b>VIi</b>) also demonstrated notable antibacterial properties. Although the overall antimicrobial efficacy of the synthesized compounds was inferior to that of the standard reference agents, the observed activities—particularly those of compound (<b>VId</b>)—indicate their potential as lead structures for further optimization and development in antimicrobial and antimalarial drug discovery.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 3","pages":"1262 - 1278"},"PeriodicalIF":1.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145161584","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":"TERT Promoter Mutation Analysis in Glioma Samples by Allele-Specific Biochip Hybridization","authors":"V. O. Varachev,&nbsp;I. O. Barinova,&nbsp;S. A. Surzhikov,&nbsp;O. Yu. Susova,&nbsp;A. A. Mitrofanov,&nbsp;I. V. Grechishnikova,&nbsp;A. S. Zasedatelev,&nbsp;A. V. Chudinov,&nbsp;T. V. Nasedkina","doi":"10.1134/S1068162024606803","DOIUrl":"10.1134/S1068162024606803","url":null,"abstract":"<p><b>Objective:</b> Somatic mutations in the promoter of the telomerase reverse transcriptase gene <i>TERT</i> can cause reactivation of telomerase, which stimulates neoplastic processes in the body. C228T and C250T mutations of the <i>TERT</i> promoter (<i>TERTp</i>) are most often found in brain gliomas, for which they are important diagnostic and prognostic markers. <b>Methods:</b> To detect <i>TERTp</i> mutations, an approach involving amplification of the promoter region and subsequent hybridization with immobilized probes on a biological microarray (biochip) has been developed. <b>Results and Discussion:</b> Using this approach, the mutational status of <i>TERTp</i> in 94 glioma samples (astrocytoma, oligodendroglioma, glioblastoma) was investigated. To verify the genotyping results, we used data from Illumina targeted sequencing and Sanger direct sequencing. In total, <i>TERTp</i> mutations were detected in 62 of 94 samples (66%), most commonly in patients with glioblastoma (71%). The C228T mutation (69%) was significantly more frequent compared to the C250T mutation (31%). <b>Conclusions:</b> The results of biochip validation on a collection of clinical samples show that it can be used as a convenient and reliable diagnostic tool in the genetic analysis of CNS tumors.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 3","pages":"1218 - 1223"},"PeriodicalIF":1.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145161564","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}