Russian Journal of Bioorganic Chemistry最新文献

{"title":"Application of Machine Learning Methods for Processing and Analyzing Data from Probe and Optical Microscopy of Biological Objects","authors":"T. O. Sergeeva,&nbsp;A. E. Efimov,&nbsp;V. V. Goncharenko,&nbsp;V. A. Oleinikov,&nbsp;I. I. Agapov","doi":"10.1134/S1068162025604902","DOIUrl":"10.1134/S1068162025604902","url":null,"abstract":"<p>This review systematizes modern machine learning (ML) methods for solving key image processing tasks in optical microscopy (OM) and atomic force microscopy (AFM). Traditional microscopy data analysis methods face problems of subjectivity, low throughput, and difficulty in quantifying multimodal information. The review discusses the use of ML for the following main tasks: segmentation of objects on OM and AFM images of biological structures; classification of samples based on morphological features; regression analysis for predicting the properties of biological objects; multiparametric data analysis combining information from various visualization channels (height, adhesion, etc.). Special attention is paid to the capabilities of ML to identify complex correlations between surface topography and functional characteristics, which is difficult in traditional analysis. The review also discusses key issues, including the need to create specialized datasets, the problem of interpretability of models, and issues of reproducibility of results.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149132983","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":"Metabolic Changes in Intestinal Microbiota During Physical Activity","authors":"R. F. Fatkhullin,&nbsp;A. V. Shestopalov,&nbsp;T. V. Grigorieva,&nbsp;D. S. Martykanova,&nbsp;N. H. Davletova,&nbsp;I. M. Kolesnikova,&nbsp;A. A. Ivanova,&nbsp;S. A. Roumiantsev","doi":"10.1134/S1068162025605051","DOIUrl":"10.1134/S1068162025605051","url":null,"abstract":"<p><b>Objective:</b> The aim of our study was to study the metabolic profile of the intestinal microbiota in combat sports athletes to identify specific enzymes and metabolic pathways associated with microbiome adaptation to intense physical activity. <b>Methods:</b> Stool samples were collected from the study participants. Bacterial DNA was isolated from the samples using the QIAamp Fast DNA Stool Mini Kit, followed by sequencing of the v3-v4 variable region of the 16S rRNA gene on the MiSeq platform. The obtained data were analyzed using QIIME v.1.9.1 using the Greengenes v.13.8 reference database with a 97% sequence similarity threshold. Metabolic functions of the intestinal microbiota were predicted using PICRUSt2 software (03), which allowed us to estimate the abundance of enzyme and metabolic pathway genes normalized to the copy number of 16S rRNA reads. Statistical processing of the obtained results was performed using GraphPad Prism v. 10.4.1. <b>Results and Discussion:</b> As a result, the presence of 2186 enzymes and 403 metabolic pathways was predicted in the metabolic profiles of the intestinal microbiota of the study groups. Among the enzymes, increased levels of aromatic amino acid decarboxylase (EC: 4.1.1.28) and pteridine reductase (EC: 1.5.1.33) were observed in the microbiome of athletes. The control group participants were not predicted to have the genes encoding these enzymes in their gut microbiomes, whereas the aromatic L-amino acid decarboxylase gene (EC: 4.1.1.28) was predicted to be present in the microbiome of 61.1% of athletes (<i>p</i> = 0.0001), and the pteridine reductase gene (EC: 1.5.1.33) was predicted to be present in the microbiome of 83.3% of athletes (<i>p</i> &lt; 0.0001). <b>Conclusions:</b> Intense physical activity leads to isolated changes in the metabolic capabilities of the gut microbiota, while the overall metabolic profile of the microbiome is similar to that of non-athletes. In athletes, the gut microbiome is more active in producing and degrading biogenic amines, synthesizing ergothioneine and methyl ketones, and exhibits specific fatty acid synthesis and pterin metabolism. These changes appear to reflect adaptation of the microbiota to intense physical activity.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035048","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":"7-R-Amino-6-(tetrazol-5-yl)azolo[1,5-a]pyrimidines as Potential CK2 Inhibitors: Synthesis and Cytotoxic Activity","authors":"G. V. Urakov,&nbsp;K. V. Savateev,&nbsp;M. D. Tokhtueva,&nbsp;V. V. Melekhin,&nbsp;A. V. Paramonova,&nbsp;V. L. Rusinov","doi":"10.1134/S1068162026600819","DOIUrl":"10.1134/S1068162026600819","url":null,"abstract":"<p><b>Objective:</b> The structure of 6-(tetrazol-5-yl)azolo[1,5-<i>a</i>]pyrimidines as inhibitors of casein kinase 2 (CK2) has been optimized by the replacement of the primary C7-amino group with a secondary amino fragment to increase the affinity for the active site of CK2. The proposed water-soluble heterocycles have been obtained by original synthetic scheme, which involved exploiting the NH-acidity of the tetrazole ring. The cytotoxic activity of the obtained water-soluble derivatives of 6-(tetrazol-5-yl)azolopyrimidines was studied on several cell lines, including cells with overexpression of CK2, lung carcinoma A-549 and hepatocellular carcinoma Hep-G2. <b>Methods:</b> An original synthetic scheme with the construction of a condensed azaheterocyclic system, chlorodeoxygenation, nucleophilic substitution of a halogen atom, and the azide-nitrile cycloaddition. The structure and purity of obtained heterocycles were confirmed by a suite of modern physico-chemical methods of analysis. Cytotoxicity was studied by MTT assay. <b>Results and Discussion:</b> It was shown that 7-oxoazolopyrimidine-6-carbonitriles could be constructed by reaction of aminoazoles and ethyl 2-cyano-3-ethoxyacrylate through intermediate enamine compounds. Further chlorodeoxygenation and nucleophilic substitution of chlorine atom <i>in situ</i> resulted in 7<i>-</i>R-aminoazolopyrimidin-6-carbonitriles. The latter were used as the substrates for azide-nitrile cycloaddition to give desired 6-(tetrazol-5-yl)azolopyrimidines. The cytotoxicity of water-soluble sodium salts of these molecules was studied on different tumor cells as well as pseudo-normal cells HEK-293. <b>Conclusions:</b> It was found that most 7<i>-</i>R-amino-6-(tetrazol-5-yl)azolo[1,5-<i>a</i>]pyrimidines exhibited a weak effect on the viability of tumor cells, probably, a special impact is required to induce programmed cell death in addition to inhibiting CK2. Sodium 5-(2-(benzylthio)-7-((4-chlorophenethyl)amino)-[1,2,4]triazolo[1,5-<i>a</i>]pyrimidin-6-yl)tetrazol-2-id demonstrated the greatest cytotoxicity against liver carcinoma cells with an IC₅₀ index &lt; 39.66 µmol/L.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035275","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":"Neutralization of Hemolytic Activity of Hemolysin II and Cytotoxin K2 of Bacillus cereus by Antibodies","authors":"O. S. Vetrova,&nbsp;N. V. Rudenko,&nbsp;A. P. Karatovskaya,&nbsp;A. V. Zamyatina,&nbsp;A. S. Nagel,&nbsp;Zh. I. Andreeva-Kovalevskaya,&nbsp;A. V. Siunov,&nbsp;F. A. Brovko,&nbsp;A. S. Solonin","doi":"10.1134/S1068162025605191","DOIUrl":"10.1134/S1068162025605191","url":null,"abstract":"<p><b>Objective:</b> <i>Bacillus cereus</i>, a gram-positive bacterium widespread in nature, can cause toxic infections in humans. Key virulence factors include hemolysin II (HlyII) and cytotoxin K2 (CytK2), which belong to the group of β-pore-forming toxins. The toxic effect occurs when the water-soluble monomeric forms of the toxins secreted by the bacterium oligomerize to form pores that disrupt the permeability of the cell membrane, leading to cell lysis. <b>Methods:</b> The study examined the suppression of toxic activity HlyII and CytK2 <i>in vivo</i> and the effect of HP-5 neutralizing antibodies on the CytK2. <b>Results and Discussion:</b> Neutralizing antibodies against hemolysins HlyII and CytK2 have been shown not to interfere with the oligomerization of monomers in the presence of the target cell membrane. Monoclonal antibodies that neutralize the hemolytic activity of CytK2 block the pore formed by the toxin on the target cell membrane, as do antibodies against the large <i>C</i>-terminal fragment of the HlyII strain, which specifically neutralize its effect. Using a mouse model, the ability of antibodies to neutralize the action of HlyII and CytK2 was demonstrated. <b>Conclusions:</b> The neutralizing antibodies being studied may form the basis for the development of therapeutic agents for the treatment of diseases caused by <i>B. cereus</i>.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035276","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":"Immunogenicity of Peptides Reproducing Conserved B-cell Epitopes of Hepatitis C Virus Antigens","authors":"M. D. Stuchinskaya,&nbsp;L. I. Nikolaeva,&nbsp;V. V. Kupriyanov,&nbsp;A. N. Belyavtsev,&nbsp;V. A. Shelkonogov,&nbsp;N. S. Shastina","doi":"10.1134/S1068162026601710","DOIUrl":"10.1134/S1068162026601710","url":null,"abstract":"<p><b>Objective:</b> Hepatitis C virus (HCV) is characterized by high genetic variability, which complicates the development of vaccines that protect against all viral genotypes and subtypes. Therefore, studying the immunogenicity of conserved B-cell epitopes is an important task. The aim of this study was to synthesize and analyze seven peptides reproducing conserved B-cell epitopes of HCV structural and nonstructural proteins: E1(313–327), E2(412–422), E2(434–446), E2(524–535), Core(1–17), NS4A(1689–1711), and NS4B(1722–1739). <b>Methods:</b> The selected peptides were obtained by solid-phase peptide synthesis using the Fmoc-strategy with high purity (&gt;95%). To enhance peptide immunogenicity, liposomal formulations based on soybean phosphatidylcholine were constructed. To evaluate immunogenicity, BALB/c mice were immunized with the following preparations: peptides in saline, peptides with incomplete Freund's adjuvant (IFA), and liposomal formulations of the peptides. Antibodies against the peptides were detected by solid-phase enzyme-linked immunosorbent assay (ELISA). <b>Results and Discussion:</b> Liposomal nanoparticles containing the peptides were homogeneous, with an average size of 170–205 nm, high peptide entrapment efficiency (61–86%), and long-term stability. Analysis of mouse sera after immunization with peptides in saline revealed no humoral immune response. The use of IFA led to antibody production against only two peptides (E2(524–535) and NS4A(1689–1711)), with low titers (up to 1:56). In contrast, immunization with liposome-encapsulated peptides induced antibody production against five peptides (E2(434–446), E2(524–535), Core(1–17), NS4A(1689–1711), and NS4B(1722–1739)), with titers ranging from 1:24 to 1:448. <b>Conclusions:</b> These results demonstrate that liposomal peptide formulations are an effective strategy for enhancing the immunogenicity of HCV B-cell epitopes. This study provides a promising foundation for the development of a multi-epitope hepatitis C vaccine.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035109","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":"II. Synthesis and Antioxidant Activity of Hydrazinecarbothioamides Based on 6-Methyluracil and Acylhydrazides","authors":"I. B. Chernikova,&nbsp;N. S. Makara","doi":"10.1134/S1068162025605282","DOIUrl":"10.1134/S1068162025605282","url":null,"abstract":"<p><b>Objective:</b> The synthesis of uracil-containing hydrazinecarbothioamides opens up new possibilities for studying their antioxidant properties. In the course of this work, the indicated compounds with high yields were successfully obtained. Their antioxidant potential has been studied in vitro using conventional techniques such as ABTS, FRAP, DPPH, and nitric oxide inhibition tests. <b>Methods:</b> The synthesis of hydrazinecarbothioamides was carried out by the method described earlier, by boiling 5-isothiocyanato-6-methyluracil and acylhydrazides in a 1,4-dioxane medium with quantitative yields. When studying the antioxidant activity in vitro of the obtained compounds, ascorbic acid and trolox were used as comparison drugs. <b>Results and Discussion:</b> The reaction of 5-isothiocyanato-6-methyluracil and acylhydrazides synthesized a series of hydrazinecarbothioamides with high yields and investigated their biological activity. During in vitro tests for antioxidant properties, it was found that compound (<b>VII</b>), which contains in its structure, in addition to 6-methyluracil and thiourea, an aromatic fragment, has the best activity against the reduction of Fe³⁺ and the radical cation ABTS. It was shown that compound (<b>XI</b>), containing an isonicotinoyl fragment in its structure, was more active in reducing the stable DPPH radical and inhibiting nitric oxide. <b>Conclusions:</b> As a result, two of the most active compounds were identified: 2-benzoyl-<i>N</i>-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-yl)hydrazinecarbothioamide (showed reducing activity against the radical cation ABTS and Fe³⁺ in EC₅₀ values of 276.31 ± 11.52 and 10.14 ± 0.45 µg/mL, respectively) and 2-isonicotinoyl-<i>N</i>-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-yl)hydrazinecarbothioamide (restored the stable radical DPPH in the EC₅₀ value of 124.28 ± 4.32 µg/ml, and also reduced the level of nitrite by 55.9% (<i>p</i> &lt; 0.05) compared with the control).</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035271","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 Immunotropic Activity of New Heterodimers with a 4-(2-Furyl)pyridine Fragment","authors":"A. S. Kutenets,&nbsp;I. V. Bibik,&nbsp;E. S. Gorokhova Ketova,&nbsp;E. Yu. Bibik,&nbsp;S. G. Krivokolysko,&nbsp;V. V. Dotsenko,&nbsp;N. A. Aksenov,&nbsp;I. V. Aksenova","doi":"10.1134/S1068162026600054","DOIUrl":"10.1134/S1068162026600054","url":null,"abstract":"<p><b>Objective:</b> The aim of this study was to identify new immunotropic compounds among nicotinonitrile and thienoquinoline derivatives conjugated with furan residues. Three new heterodimeric molecules were synthesized: 5-cyano-6-({2-[(4-ethoxyphenyl)amino]-2-oxoethyl}thio)-4-(2-furyl)-2-methyl-<i>N</i>-(2-methylphenyl)-1,4-dihydropyridine-3-carboxamide (<b>XI</b>), ethyl 4-(6-({2-[(3,5-dichlorophenyl)amino]-2-oxoethyl}thio)-5-cyano-4-(2-furyl)-2-methyl-1,4-dihydropyridine-3-carboxamido)benzoate (<b>XII</b>), and (3-amino-4-(5-methyl-2-furyl)-5,6,7,8-tetrahydrothieno[2,3-<i>b</i>]quinolin-2-yl)methanone (<b>XV</b>). <b>Methods:</b> The compounds were synthesized via reactions of cyanothioacetamide with furfural (or 5-methylfurfural), subsequent treatment with <i>N</i>-arylacetoacetamides or 1-(morpholino)cyclohexene and S-alkylation. The structures were confirmed by IR, ¹H, and ¹³C NMR spectroscopy, including 2D NMR experiments. Immunotropic activity was evaluated <i>in vivo</i> in Wistar rats with streptozotocin- and dexamethasone-induced diabetes. The test compounds were administered intragastrically at 1.5 mg/kg for 14 days. Thymus mass (absolute and relative) and histological structure were assessed. <b>Results and Discussion:</b> The synthesized heterodimers significantly increased the absolute and relative thymus mass by 53–87% and 50–90%, respectively, compared to intact animals in both diabetes models. 5-Сyano-6-({2-[(4-ethoxyphenyl)amino]-2-oxoethyl}thio)-4-(2-furyl)-2-methyl-<i>N</i>-(2-methylphenyl)-1,4-dihydropyridine-3-carboxamide showed the most pronounced effect, inducing mitotic activity of thymocytes in the subcapsular cortex and promoting their migration into the bloodstream, indicative of immunostimulatory properties. <i>In silico</i> predictions suggested potential targets for the studied compounds (LFA-1, TBK1, TLR, PPARγ, JAK, RORγ, Ras-specific nucleotide exchange factors), which may underlie the observed immunotropic effects. <b>Conclusions:</b> The novel furan–pyridine heterodimers exhibit significant immunotropic activity, with 5-cyano-6-({2-[(4-ethoxyphenyl)amino]-2-oxoethyl}thio)-4-(2-furyl)-2-methyl-<i>N</i>-(2-methylphenyl)-1,4-dihydropyridine-3-carboxamide being the most promising immunostimulant for potential use in immunosuppressive conditions of various origins. These findings support further research on nicotinonitrile-based hybrid molecules as immunomodulators.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035273","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, Biological Properties, and Docking Study of 5-Substituted 6-Methyl-2-[(E)-2-(aryl)ethenyl]pyrimidin-4(3H)-ones","authors":"Z. A. Hovasyan,&nbsp;R. A. Madoyan,&nbsp;A. G. Sukiasyan,&nbsp;A. A. Hambardzumyan,&nbsp;A. S. Sargsyan,&nbsp;M. Y. Danghyan,&nbsp;A. A. Shahkhatuni,&nbsp;G. Sh. Hovhannisyan,&nbsp;A. A. Harutyunyan","doi":"10.1134/S1068162025604422","DOIUrl":"10.1134/S1068162025604422","url":null,"abstract":"<p><b>Objective:</b> By condensation of 5-substituted 2,6-dimethylpyrimidin-4(3<i>H</i>)-ones with aromatic aldehydes, 5-substituted 6-methyl-2-[(<i>E</i>)-2-(aryl)ethenyl]pyrimidin-4(3<i>H</i>)-ones were obtained. By chlorination of 5-pentyl-2-(4-bromophenyl)ethenyl) derivative followed by treatment with dimethylamine, 4-dimethylamino derivative was synthesized, isolated as picrate. <b>Methods:</b> Chemical synthesis. <b>Results and Discussion:</b> The antimicrobial and antifungal properties of the synthesized compounds and known drugs were studied against <i>Staphylococcus aureus</i> and <i>Escherichia coli</i> bacteria and <i>Candida albicans</i> fungus. A docking study was performed against four targets: the RNA-dependent RNA polymerase (RdRp) complex with the NSP7 and NSP8 proteins of the SARS-CoV-2 virus, the kinase domain of the human epidermal growth factor receptor (EGFR), doubly phosphorylated human mitogen-activated protein kinase 14 (MAPK14) in complex with the activator of transcription factor (ATF2), and human monoamine oxidase B in complex with 2-(2-benzofuranyl)-2-imidazoline. (2-BFI). <b>Conclusions:</b> It was shown that the size of the substituent at position 5 of 2-styrylpyrimidines leads to the emergence of significant antifungal activity in the compounds, in the absence of antibacterial activity. Docking studies of the synthesized pyrimidines did not reveal the predicted activity against the used targets, although the obtained Δ<i>G</i>_o values are comparable to those for known drugs with a similar pharmacological profile. The obtained results indicate the potential of searching for compounds with antifungal activity in the 2-styrylpyrmidine series.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035277","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":"NMR Structure and Dynamics of the Starfish Three-Finger Protein Lystar5","authors":"A. S. Paramonov,&nbsp;M. A. Shulepko,&nbsp;A. M. Chernikov,&nbsp;M. P. Kirpichnikov,&nbsp;E. N. Lyukmanova,&nbsp;Z. O. Shenkarev","doi":"10.1134/S1068162025605002","DOIUrl":"10.1134/S1068162025605002","url":null,"abstract":"<p><b>Objective:</b> The primary goal of this study was to determine the spatial structure and investigate the intramolecular dynamics of Lystar5, the first functionally characterized three-finger protein (TFP) from the starfish <i>Asterias rubens</i>. <b>Methods:</b> Spatial structure determination was performed using 2D and 3D homo- and heteronuclear NMR. Intramolecular dynamics data (mobility in the pico-nanosecond and micro-millisecond ranges) were obtained by measuring ¹⁵N NMR relaxation parameters (R₁, R₂, and ¹⁵N-{¹H}-NOE) with subsequent model-free analysis. <b>Results and Discussion:</b> The NMR data confirmed that Lystar5 adopts a classic \"three-finger\" fold stabilized by six disulfide bonds. The structure features two β-sheets: a small one in loop I and a larger one formed by four strands from all three loops, along with an α-helix in loop III. The molecular surface is mainly hydrophilic, containing two major clusters of negatively charged groups. Dynamics studies indicated that while the protein backbone is generally stable in the pico-nanosecond range, sections of loops I and II exhibit conformational exchange on the micro-millisecond timescale. Although the Lystar5 fold is similar to the human protein Lynx2, their distinct physicochemical properties and dynamics suggest different molecular targets and mechanisms of action. <b>Conclusions:</b> This work provides the first detailed structural and dynamic characterization of an echinoderm TFP. Understanding the relationship between the structure and dynamics of Lystar5 will facilitate the study of its interactions with human nicotinic acetylcholine receptors and integrins. These data open opportunities for the rational design of new biomedical drugs, specifically aimed at stimulating cell migration for wound healing.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035272","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, Molecular Docking, and ADMET Evaluation of Novel Quinazolinone-Coumarin Hybrid Derivatives as Dual Inhibitors of Urease and Acetylcholinesterase","authors":"Nedime Çalışkan,&nbsp;Gülay Akyüz,&nbsp;Fatih İslamoğlu,&nbsp;Emre Menteşe","doi":"10.1134/S1068162026600650","DOIUrl":"10.1134/S1068162026600650","url":null,"abstract":"<p><b>Objective:</b> In this study, new amide-bridged quinazolinone and coumarin hybrid compounds were synthesized. The characterization of these compounds was carried out using spectral data such as FT-IR, ¹H NMR, ¹³C NMR, and elemental analysis. Enzyme inhibition properties of the compounds were investigated against both urease and acetylcholinesterase enzymes. <b>Methods:</b> Compounds <b>2a–2g</b> were dissolved in benzene, and coumarin derivatives were added. The reaction mixture was heated under reflux for the synthesis of compounds <b>4a–4n</b>. Enzyme inhibition studies were carried out using the Weatherburn method for urease and the Ellman method for acetylcholinesterase. The structures were further elucidated through molecular docking studies. <b>Results and Discussion:</b> While all synthesized compounds exhibited acetylcholinesterase inhibition, urease inhibition was observed only in some of the compounds. Molecular docking studies were performed to evaluate the binding affinities of the compounds against AChE and urease enzymes. The docking results were evaluated based on the scoring function of AutoDock Vina. The reported values represent relative binding affinity scores rather than absolute binding free energies. All tested compounds exhibited favorable binding affinities toward both enzymes, with compound <b>4a</b> showing a significant docking score against AChE (11.4) and compound <b>4d</b> against urease (11.0). Interaction analyses revealed that these ligands maintain high conformational fit and stability through hydrogen bonds and various π-interactions, suggesting the potential of specific derivatives as potent dual inhibitors. ADMET predictions showed that most compounds exhibited good gastrointestinal absorption, low blood-brain barrier permeability (which is desirable for peripheral targets), and an acceptable toxicity profile. <b>Conclusions:</b> In particular, compound <i>N</i>-(4-oxo-2-(3-bromobenzyl)-6-methyl-2-oxo-quinazolin-3(4<i>H</i>)-yl)-2<i>H</i>-chromene-3-carboxamide (<b>4d</b>) showed an IC₅₀ value of 11.50 ± 0.15 µg/mL for urease inhibition, whereas this value was 14.50 ± 0.10 µg/mL for acetylcholinesterase. These findings demonstrate that this compound exhibits inhibitory activity against both enzymes.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 5","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035108","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}