Russian Journal of Bioorganic Chemistry最新文献

{"title":"Synthetic Analogs of Ganglioside GD2 for the Study of Its Cluster and Multivalent Interactions with Antibodies","authors":"M. S. Sokolova,&nbsp;E. M. Rapoport,&nbsp;V. A. Zubricheva,&nbsp;R. V. Kholodenko,&nbsp;A. S. Paramonov,&nbsp;S. V. Khaidukov,&nbsp;N. V. Bovin,&nbsp;I. M. Ryzhov","doi":"10.1134/S1068162026600170","DOIUrl":"10.1134/S1068162026600170","url":null,"abstract":"<p><b>Objective:</b> Ganglioside GD2 is a tumor-associated antigen, and several monoclonal anti-GD2 antibodies are currently used in the treatment of high-risk pediatric neuroblastoma. The development of new therapeutics of this class requires a detailed understanding of the mechanisms underlying the interaction between ganglioside GD2 and antibodies, including the influence of the membrane environment. <b>Methods:</b> These factors include cluster (binding of one Fab fragment of an antibody to several ganglioside molecules) and multivalent (binding of different Fab fragments of one antibody to several ganglioside molecules) interactions. To investigate the possibility of such interactions, two analogs of ganglioside GD2 containing several glycan fragments were synthesized, and their binding to anti-GD2 antibodies was evaluated by flow cytometry. <b>Results and Discussion:</b> Two synthetic glycolipids, (GD2)₂-D-Ad-DOPE and (GD2)₃-T17-DOPE, containing two and three GD2 carbohydrate moieties, respectively, were successfully synthesized. When incorporated into the cell membrane, both constructs exhibited significantly higher binding to anti-GD2 antibodies compared to their monovalent analogs. The (GD2)₂-D-Ad-DOPE construct, featuring a “tight” glycocluster that models ganglioside clustering, showed the most pronounced binding, significantly exceeding that of its monovalent counterpart. The (GD2)₃-T17-DOPE construct also exhibited increased binding, attributed to a multivalent interaction effect. These findings indicate that anti-GD2 antibodies preferentially recognize clustered GD2 molecules rather than individual gangliosides. <b>Conclusions:</b> The obtained results support the hypothesis that anti-GD2 antibodies target dynamic clusters of gangliosides within membrane rafts rather than individual molecules. The cluster effect of antibody recognition was shown to be more pronounced than the multivalent effect. This study opens new perspectives in the search for complex targets for anticancer therapeutics.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148281800","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":"Unlocking the Therapeutic Potential of Heterocyclic Molecules as SIRT2 Inhibitors: Advancing Therapeutic Frontiers","authors":"Arti Soni,&nbsp;Vivek Kumar,&nbsp;Daisy Arora,&nbsp;Rohit Bhatia,&nbsp;Neelam Malik","doi":"10.1134/S1068162025602873","DOIUrl":"10.1134/S1068162025602873","url":null,"abstract":"<p>Silent information regulators (sirtuins) are nicotinamide adenine dinucleotide (NAD⁺)-dependent enzymes that participate in numerous physiological processes in humans. Among the seven human sirtuins, sirtuin 2 (SIRT2) is one of the most extensively characterized isoforms, playing a pivotal role in cellular aging, energy metabolism, and genomic stability. This review summarizes recent advances in the development of small-molecule SIRT2 inhibitors, highlighting their half-maximal inhibitory concentrations (IC₅₀ values). A concise structure–activity relationship (SAR) analysis explores the critical pharmacophores and chemical probes responsible for SIRT2 inhibition, providing insights for lead optimization and the design of novel therapeutics. This comprehensive overview is expected to facilitate the rational design of next-generation, highly potent, and selective SIRT2 inhibitors.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148281866","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":"Recombinant Proteins Containing Hepatitis C Virus Protein Epitopes Fused with One, Two, or Three Copies of a Lipopeptide Form Nanoparticles of Different Sizes and Differing in Immunological Properties","authors":"V. V. Kupriyanov,&nbsp;L. I. Nikolaeva,&nbsp;A. A. Zykova,&nbsp;M. D. Stuchinskaya,&nbsp;E. A. Blokhina,&nbsp;N. V. Ravin","doi":"10.1134/S1068162025604975","DOIUrl":"10.1134/S1068162025604975","url":null,"abstract":"<p><b>Objective:</b> Viral hepatitis C is a widespread infectious disease that often follows a prolonged chronic course. The development of a prophylactic and therapeutic vaccine is an urgent task to reduce the incidence of chronic hepatitis C. The aim of this study was to generate recombinant proteins with enhanced immunogenicity capable of eliciting an effective immune response, which could serve as a basis for designing a therapeutic vaccine. <b>Methods:</b> Using genetic engineering methods, we constructed recombinant proteins containing lipopeptide sequences derived from <i>Neisseria meningitidis</i>, a T-helper epitope of the viral core protein, and cytotoxic epitopes of the NS4B protein. The proteins were purified by metal affinity chromatography on Ni-NTA-agarose. Dynamic light scattering and electron microscopy were used to assess nanoparticle formation. <b>Results and Discussion:</b> A triple repeat of the lipopeptide sequence within the recombinant protein structure leads to the formation of nanoparticles approximately 50–100 nm in size. Immunological analysis performed on splenocytes from immunized mice and activated human peripheral blood lymphocytes showed that nanoparticle formation significantly enhances the immunogenicity of the NS4B epitopes. <b>Conclusions:</b> The obtained data may be used in the development of a therapeutic vaccine against the hepatitis C virus.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148281864","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, Docking, and Biological Properties of N- and O-Acyl Derivatives of 2-Aryl-substituted Quinolinecarboxylic Acids","authors":"N. Z. Hakobyan,&nbsp;A. S. Grigoryan,&nbsp;R. A. Madoyan,&nbsp;A. G. Sukiasyan,&nbsp;T. A. Ambartsumyan,&nbsp;M. Yu. Danghyan,&nbsp;A. A. Hambardzumyan,&nbsp;A. A. Harutyunyan","doi":"10.1134/S1068162025604161","DOIUrl":"10.1134/S1068162025604161","url":null,"abstract":"<p><b>Objective:</b> To synthesize novel <i>N</i>- and <i>O</i>-acylated derivatives of 2-arylquinoline-4-carboxylic acids (analogues of Atophan), evaluate their anti-monoamine oxidase, antibacterial, and fungicidal activities, perform molecular docking against several biological targets (RdRp of SARS-CoV-2, EGFR, MAPK14, and MAO-B), and identify lead compounds for further development. <b>Methods: </b><i>N</i>-Acylated derivatives (amides and diamides) were obtained by reacting 2-arylquinoline-4-carbonyl chlorides with primary amines or diamines. <i>O</i>-Acylated derivatives (1,3-benzothiazol-2-ylmethyl and naphthyl esters) were synthesized by heating the corresponding alcohols (1,3-benzothiazol-2-ylmethanol or naphthols) with acid chlorides in anhydrous benzene. The structures were confirmed by ¹H, ¹³C NMR, and IR spectroscopy. Anti-monoamine oxidase activity was studied on a rat brain homogenate model <i>in vitro</i> using serotonin (5-OT) as a substrate. Antibacterial and antifungal activities were assessed against <i>E. coli</i>, <i>S. aureus</i>, and <i>C. albicans</i> using the agar diffusion method. Molecular docking was performed to calculate the Gibbs free energy (Δ<i>G</i>°) of binding to RdRp (pdb 7btf), EGFR (pdb 3w32), MAPK14 (pdb 6zqs), and MAO-B (pdb 4a7a). <b>Results and Discussion:</b> A series of <i>N</i>-substituted 2-arylquinoline-4-carboxamides (<b>9–21</b>), diamides (<b>22</b>, <b>23</b>), 1,3-benzothiazol-2-ylmethyl esters (<b>24, 25</b>), and naphthyl esters (<b>26–28</b>) were synthesized. Amides <b>10</b> and <b>17</b> activated MAO-A by 19 and 10%, respectively (1·10^–6 mol/mL), while esters <b>25</b> and <b>28</b> exhibited potent anti-MAO activity (92 ± 6.3 and 91 ± 5.0% inhibition of serotonin deamination), outperforming the reference drug indopan (86 ± 6.0%). Compounds <b>14</b> and <b>19</b> showed high antibacterial activity against all tested strains. Compound <b>19</b> also demonstrated pronounced antifungal activity comparable to fluconazole (28 mm inhibition zone <i>vs</i>. 30 mm for fluconazole). Docking studies revealed that compounds <b>23</b> and <b>27</b> have the highest affinity for MAPK14 (Δ<i>G</i>° = –12.027 and –12.580 kcal/mol), while all tested compounds interacted weakly with MAO-B (Δ<i>G</i>° = –7 to –9 kcal/mol) and RdRp (Δ<i>G</i>° = –7 to –8 kcal/mol). Compounds <b>24</b> and <b>26</b> showed no significant biological activity in the assays used. <b>Conclusions:</b> Derivatives <b>25</b>, <b>28</b>, <b>14</b>, <b>19</b>, <b>23</b>, and <b>27</b> are promising lead compounds for further development as antidepressants, antibacterial, antifungal, and anticancer agents. The study confirms that the Atophan scaffold is a valuable basis for designing multitarget bioactive molecules.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148281129","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, Docking, and Biological Properties of 2-Phenyl-5,6,7,8-tetrahydroquinazoline-4(3H)-thione Derivatives","authors":"M. S. Safaryan,&nbsp;R. A. Madoyan,&nbsp;A. G. Sukiasyan,&nbsp;A. G. Ayvazyan,&nbsp;A. A. Mnatsakanyan,&nbsp;M. Yu. Danghyan,&nbsp;A. A. Hambardzumyan,&nbsp;A. A. Harutyunyan","doi":"10.1134/S1068162025604410","DOIUrl":"10.1134/S1068162025604410","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Objective:&lt;/b&gt; The aim of this study was to synthesize &lt;i&gt;S&lt;/i&gt;-alkylated and hybrid derivatives of 2-phenyl-5,6,7,8-tetrahydroquinazoline-4(3&lt;i&gt;H&lt;/i&gt;)-thione, evaluate their antibacterial and antifungal properties, and perform a docking study against four molecular targets: RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2, epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 14 (MAPK14), and monoamine oxidase B (MAO-B). &lt;b&gt;Methods:&lt;/b&gt; The starting 2-phenyl-5,6,7,8-tetrahydroquinazoline-4(3&lt;i&gt;H&lt;/i&gt;)-thione &lt;b&gt;1&lt;/b&gt; was alkylated with 2-halogen-1-(aryl)ethan-1-ones &lt;b&gt;2a–2c&lt;/b&gt;, &lt;i&gt;N&lt;/i&gt;-substituted chloroacetamides &lt;b&gt;2d–2e&lt;/b&gt;, and 4-methoxy-3-chloromethylbenzaldehyde &lt;b&gt;4&lt;/b&gt; to give &lt;i&gt;S&lt;/i&gt;-alkylated derivatives &lt;b&gt;3a–3e&lt;/b&gt; and &lt;b&gt;5&lt;/b&gt;. Compound &lt;b&gt;5&lt;/b&gt; was further condensed with 2-thioxothiazolidin-4-one &lt;b&gt;6&lt;/b&gt; to afford quinazoline-thiazolidine hybrid &lt;b&gt;7&lt;/b&gt;, and with 2-amino-4,5,6,7-tetrahydrobenzo[&lt;i&gt;b&lt;/i&gt;]thiophene-3-carboxamide &lt;b&gt;8&lt;/b&gt; to give quinazoline-benzo[4,5]thieno[2,3-&lt;i&gt;d&lt;/i&gt;]pyrimidin-4(3&lt;i&gt;H&lt;/i&gt;)-one hybrid &lt;b&gt;9&lt;/b&gt;. Reaction of &lt;b&gt;5&lt;/b&gt; with ethyl cyanoacetate &lt;b&gt;10&lt;/b&gt; and substituted acetophenones &lt;b&gt;11a–11d&lt;/b&gt; yielded chalcones &lt;b&gt;12a–12e&lt;/b&gt;, which were cyclized with benzamidine hydrochloride &lt;b&gt;13&lt;/b&gt; into quinazoline-pyrimidine hybrids &lt;b&gt;14a–14b&lt;/b&gt;. All compounds were characterized by IR, NMR, and mass spectrometry, and X-ray diffraction (for &lt;b&gt;5&lt;/b&gt;). Antibacterial activity against &lt;i&gt;E. coli&lt;/i&gt; and &lt;i&gt;S. aureus&lt;/i&gt; and antifungal activity against &lt;i&gt;C. albicans&lt;/i&gt; were tested using the agar diffusion method. Molecular docking was performed using AutoDock Vina. &lt;b&gt;Results and Discussion:&lt;/b&gt; &lt;i&gt;S&lt;/i&gt;-alkylated derivatives &lt;b&gt;3a–3e&lt;/b&gt; showed moderate to good antibacterial and antifungal activity. Compound &lt;b&gt;3c&lt;/b&gt; (3-nitrophenyl) was active against &lt;i&gt;E. coli&lt;/i&gt; and &lt;i&gt;C. albicans&lt;/i&gt;, while hybrid &lt;b&gt;7&lt;/b&gt; exhibited pronounced antifungal properties. Chalcones &lt;b&gt;12b–12e&lt;/b&gt; and pyrimidines &lt;b&gt;14a–14b&lt;/b&gt; showed activity against &lt;i&gt;S. aureus&lt;/i&gt;. Docking studies revealed that all synthesized compounds bind strongly to RdRp of SARS-CoV-2 with Δ&lt;i&gt;G&lt;/i&gt;° values from –7.0 to –9.0 kcal/mol; hybrid &lt;b&gt;14b&lt;/b&gt; showed the highest affinity (Δ&lt;i&gt;G&lt;/i&gt;° of –9.4 kcal/mol), comparable to remdesivir (–8.19 kcal/mol). Against EGFR, derivatives &lt;b&gt;3d–3e&lt;/b&gt; displayed Δ&lt;i&gt;G&lt;/i&gt;° below –10.0 kcal/mol, while hybrids &lt;b&gt;14a–14b&lt;/b&gt; showed Δ&lt;i&gt;G&lt;/i&gt; below –11.0 kcal/mol, surpassing erlotinib and gefitinib and approaching lapatinib (–11.25 kcal/mol). Hybrid &lt;b&gt;9&lt;/b&gt; demonstrated exceptional binding to MAPK14 with Δ&lt;i&gt;G&lt;/i&gt;° of –13.15 kcal/mol, significantly stronger compared to known inhibitors such as dabrafenib and vemurafenib (Δ&lt;i&gt;G&lt;/i&gt;° from –7.52 to –10.40 kcal/mol). Against MAO-B, all compounds showed moderate affinity (Δ&lt;i&gt;G&lt;/i&gt;° from –6.78 to –8.99 kcal/mol), comparable to clinical inhibitors moclobemide and selegiline. &lt;b&gt;Conclusions:&lt;/b&gt; A series of &lt;i&gt;S&lt;/i&gt;-alkylated and hybrid deriv","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148281280","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":"Novel Imine Derivatives of 1,2,4-Triazole-3-thione: Synthesis, Characterization, Antimicrobial Activities, and ADME Profile Investigation","authors":"Palak I. Vaja,&nbsp;Mehul R. Chauhan,&nbsp;Satish M. Ghelani","doi":"10.1134/S1068162025602757","DOIUrl":"10.1134/S1068162025602757","url":null,"abstract":"<p><b>Objective:</b> A series of novel imine derivatives of 1,2,4-triazole-3-thione <b>TAS-01–TAS-10</b> was synthesized from 2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylic acid <i>via</i> a multi-step sequence, culminating in acid-catalyzed condensation with various substituted benzaldehydes. <b>Methods:</b> The structures of the synthesized compounds were established using HRMS, FT-IR, and ¹H and ¹³C NMR spectroscopy. <i>In silico</i> ADME profiling using the SwissADME platform revealed strict compliance with Lipinski’s rule of five; however, high topological polar surface area (TPSA &gt;140 Ų) and low predicted gastrointestinal absorption suggested limited oral bioavailability. <i>In vitro</i> antimicrobial evaluation <i>via</i> the agar well diffusion method against Gram-positive (<i>Staphylococcus aureus</i>, <i>Bacillus subtilis</i>) and Gram-negative (<i>Pseudomonas aeruginosa</i>, <i>Salmonella typhimurium</i>) bacterial strains, using streptomycin as a positive reference, revealed distinct antibacterial profiles. <b>Results and Discussion:</b> Derivatives <b>TAS-04</b>, <b>TAS-07</b>, and <b>TAS-09</b> exhibited pronounced inhibitory effects against Gram-positive bacteria, generating zones of inhibition (ZOI) of 20.0–22.0 mm (streptomycin: 36.0–44.7 mm). Conversely, compounds <b>TAS-02</b>, <b>TAS-05</b>, and <b>TAS-08</b> demonstrated notable activity against Gram-negative strains, with ZOIs ranging from 10.3 to 13.3 mm (streptomycin: 32.3–41.3 mm). Although less potent than the standard antibiotic, these hybrids represent promising leads for further structural optimization aimed at enhancing membrane permeability and therapeutic efficacy. <b>Conclusions:</b> A novel series of 1,2,4-triazole-3-thione Schiff bases was synthesized, demonstrating substituent-modulated <i>in vitro</i> antibacterial activity against Gram-positive and Gram-negative pathogens. Although <i>in silico</i> profiling highlighted low oral bioavailability due to elevated TPSA, these triazole–thiazole hybrids establish a viable structural platform for further optimization <i>via</i> prodrug strategies or polarity reduction to enhance membrane permeability.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148172254","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":"Synthetic Antimicrobial Peptides. VI. Antifungal Activity of Histidine-containing Peptides against Various Pathogenic and Opportunistic Species of Candida Fungi","authors":"N. V. Amirkhanov,&nbsp;A. V. Bardasheva,&nbsp;N. V. Tikunova,&nbsp;V. N. Silnikov","doi":"10.1134/S1068162025604173","DOIUrl":"10.1134/S1068162025604173","url":null,"abstract":"<p><b>Objective:</b> The synthesis and comparative screening of antifungal activity of de novo constructed histidine-containing synthetic antimicrobial peptides (SAMP) H10, H16, F2H16, and H16F2 was carried out in relation to the most common and active species of pathogenic and opportunistic fungi of the genus <i>Candida</i>. <b>Methods:</b> During the experiments, the studied strains were divided into two groups. The minimum inhibitory concentration (MIC) of the peptides was determined against strains of <i>C. albicans</i>, <i>C. glabrata</i>, <i>C. parapsilosis</i>, <i>C. tropicalis</i>, <i>C. auris,</i> and <i>C. lusitaniae</i>. <b>Results and Discussion:</b> The studied strains were stratified into a first, most aggressive group (average MIC &gt; 4 μmol) and a second, less aggressive group (MIC ≤ 4 μmol). Histidine-containing peptides were shown to exhibit selective activity against certain species of fungal cultures, depending on the number of His residues. Peptide H16 (16 His) showed increased activity against aggressive strains like <i>C. parapsilosis</i> (3759), <i>C. parapsilosis</i> (2555), and <i>C. auris</i> (9771) (MIC = 1.6, 3.1, and 3.1 μmol), which is more than 23, 6, and 16 times higher than the activity of the H10 peptide against the same cultures, respectively. Conversely, peptide H10 showed increased activity against highly aggressive strains such as <i>C. glabrata</i> (3097) and <i>C. glabrata</i> (2563) (MIC = 1.6 and 1.6 μmol), which was more than 11 and 7 times higher than the activity of peptide H16 against the same strains, respectively. Peptides H10 and H16, due to their low hydrophobicity, exhibit low hemolytic toxicity, and peptide H10 has practically zero hemolytic toxicity. It is particularly noteworthy that the efficacy of peptide H16 and its antifungal activity against <i>C. auris</i> (MIC = 1.6 μmol) was more than 30 times higher than the control antifungal peptide P113, and even 1.5 times higher than the efficacy of the most active known antifungal agent, Amphotericin B. <b>Conclusions:</b> Peptides H10 and H16, due to their high antifungal properties and low hemolytic toxicity, can be used as promising synthetic antifungal peptide drugs against a wide range of both pathogenic and opportunistic fungal cultures of the genus <i>Candida</i>. Peptide H10 can be successfully used against such an aggressive species as <i>C. glabrata</i>, while the H16 peptide is effective against <i>C. parapsilosis</i> and especially against <i>C. auris</i>. Peptides H10 and H16 can be represented as some of the most promising antifungal peptide drugs not only due to their high antifungal activity, low hemolytic toxicity, and high therapeutic significance, but also in terms of the cost-effectiveness of their synthesis, since they represent a homogeneous sequence consisting of only one histidine amino acid residue.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148172253","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 Structurally Tailored 4H-Pyran Derivatives as Potent Therapeutics for Precision Gastric Cancer Targeting","authors":"Shichao Yan,&nbsp;Zuojun Qu,&nbsp;Junpeng Chi,&nbsp;Zhe Xu,&nbsp;Aifeng Yang,&nbsp;Zhen Lv,&nbsp;Hong Li","doi":"10.1134/S1068162025602769","DOIUrl":"10.1134/S1068162025602769","url":null,"abstract":"<p><b>Objective:</b> To discover novel small-molecule anticancer agents, we designed and synthesized a series of structurally diverse 4<i>H</i>-pyran derivatives <b>2a–2g</b> and evaluated their antiproliferative activity against human gastric cancer cells. <b>Methods:</b> A one-pot multicomponent reaction strategy was systematically optimized by screening solvents, catalyst loadings, reaction times, and reactant molar ratios. The optimized protocol—utilizing 4-dimethylaminopyridine (DMAP) as an organocatalyst in ethanol—afforded the target heterocycles under mild conditions within 20 min in high yields (80–91%). Structure–activity relationship (SAR) analysis revealed that the electronic properties and regiochemistry of the phenyl ring substituents heavily dictated both synthetic efficiency and cytotoxicity. <b>Results and Discussion:</b> Notably, the <i>para</i>-fluoro <b>2a</b> and <i>para</i>-methyl <b>2d</b> derivatives exhibited the most potent antiproliferative effects against SGC-7901 cells, with half-maximal inhibitory concentrations (IC₅₀) values of 10.81 ± 0.32 and 12.73 ± 0.24 μM, respectively, significantly outperforming the reference flavonoid apigenin (IC₅₀ = 29.47 ± 0.27 μM). These findings underscore the dual role of electronic effects in modulating chemical reactivity and biological efficacy. <b>Conclusions:</b> establishing a rapid, sustainable synthetic framework and identifying promising lead candidates for preclinical anticancer drug development.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148172255","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":"Therapeutic Potential and Mechanism of Action of a New Cathelicidin from the Chacoan Peccary (Catagonus wagneri)","authors":"I. A. Bolosov,&nbsp;V. N. Safronova,&nbsp;O. V. Korobova,&nbsp;A. I. Borzilov,&nbsp;T. V. Ovchinnikova,&nbsp;P. V. Panteleev","doi":"10.1134/S106816202660162X","DOIUrl":"10.1134/S106816202660162X","url":null,"abstract":"<p><b>Objective:</b> Proline-rich antimicrobial peptides (PrAMPs) are a specific class of host-defense peptides whose primary mechanism of action involves the inhibition of bacterial ribosomes. The peccaries (<i>Tayassuidae</i>) represent a separate family of non-ruminant even-toed ungulates, belonging to the suborder <i>Suina</i>. <b>Methods:</b> In this study, we used bioinformatics approaches to discover a new cathelicidin from the Chaco peccary (<i>Catagonus wagneri</i>), consisting of 28 amino acid residues and named CwBac28. Its mechanism of action was investigated using a combination of biochemical assays and flow cytometry. <b>Results and Discussion:</b> Although peccaries are evolutionarily closely related to pigs, the closest homologs of the CwBac28 peptide were identified in representatives of the suborder <i>Cetancodonta</i>, which includes the family <i>Hippopotamidae</i> and the infraorder <i>Cetacea</i>. Cathelicidin CwBac28, similar to the well-known bovine PrAMP Bac7, is capable of efficiently inhibiting bacterial translation; however, unlike the latter, it is effective in penetrating bacterial cells lacking the functional transporter protein SbmA without disrupting the integrity of the cytoplasmic membrane of the cells. <b>Conclusions:</b> The broad spectrum of antibacterial activity and demonstrated therapeutic efficacy of CwBac28 in a mouse model of bacterial septicemia make this peptide a promising candidate for the development of new antibiotics.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147872396","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":"Biodiversity and Antimicrobial Activities of Bac7-Like Cathelicidins from Cetartiodactyls","authors":"P. V. Panteleev,&nbsp;I. A. Bolosov,&nbsp;O. V. Korobova,&nbsp;A. I. Borzilov,&nbsp;T. V. Ovchinnikova","doi":"10.1134/S1068162026601618","DOIUrl":"10.1134/S1068162026601618","url":null,"abstract":"<p><b>Objective:</b> About half of conventional antibiotics target the bacterial translation apparatus, and many of them play an important role in modern medicine. New-generation translation inhibitors must demonstrate high efficacy against clinically significant antibiotic-resistant bacterial pathogens. It is also imperative that they possess mechanisms of action that differ from those of known antibiotics, thereby reducing the likelihood of cross-resistance. One class of compounds of particular interest is animal-derived proline-rich antimicrobial peptides (PrAMPs). <b>Methods:</b> In this study, we screened 12 natural homologs of previously described cathelicidin Bac7 from <i>Bos taurus</i>, which were discovered through bioinformatic analysis of the genomes of <i>Cetartiodactyla</i> mammals, for their antibacterial activity and ability to inhibit translation. <b>Results and Discussion:</b> A structure-activity relationship analysis enabled the identification of two new homologs that exhibited pronounced activity against bacteria lacking key PrAMP transporter proteins. The high therapeutic potential of the new peptides was demonstrated in an animal model of bacterial septicemia. <b>Conclusions:</b> It has been demonstrated that the analysis of naturally-occurring combinatorial PrAMP libraries is a powerful approach for the search for new valuable antibacterial agents and provides a rich information resource for the development of new antibiotics by modifying the structures of well-known AMPs with a characterized mechanism of action.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 4","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147872283","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}