Russian Journal of Bioorganic Chemistry最新文献

{"title":"Synthesis, Bioactive Evaluation, and Preliminary Antibacterial Mechanism Study of Novel Ferulic Acid Derivatives","authors":"Song Bai,&nbsp;Miao Li,&nbsp;Rong Wu,&nbsp;Shouying Tang,&nbsp;Fang Wang,&nbsp;Lijun Chen,&nbsp;Xian Wei,&nbsp;Shuang Feng,&nbsp;Miaohe Zhang,&nbsp;Suran Wan","doi":"10.1134/S1068162024606189","DOIUrl":"10.1134/S1068162024606189","url":null,"abstract":"<p><b>Objective:</b> The aim of this study was to design and synthesize a series of ferulic acid derivatives containing amide moieties and to evaluate their activity against plant pathogenic bacteria. <b>Methods:</b> The structures of the synthesized compounds (<b>IIIa–IIIy</b>) were thoroughly characterized using ¹H, ¹³C NMR, and HR-MS techniques. The antibacterial activity of the target compounds against <i>Xanthomonas oryzae</i> pv. <i>oryzicola</i> (<i>Xoc</i>), <i>Pseudomonas syringae</i> pv. <i>actinidiae</i> (<i>Psa</i>), and <i>Xanthomonas axonopodis</i> pv. <i>citri</i> (<i>Xac</i>) was evaluated <i>in vitro</i> using the turbidity method. <b>Results and Discussion:</b> The bioassay results indicated that some of the target compounds exhibited enhanced inhibitory activity against the tested phytopathogenic bacteria. In particular, compound (<b>IIId</b>) demonstrated potent activity against <i>Xoc</i>, with an EC₅₀ value of 24.4 μg/mL, which is more than three times more active than the reference agent thiodiazole copper (EC₅₀ = 86.7 μg/mL). Additionally, compound (<b>IIId</b>) showed significant antibacterial activity against <i>Psa</i>, with an EC₅₀ of 55.4 μg/mL, outperforming the reference compound zinc thiazole (EC₅₀ = 102.2 μg/mL). Mechanistic studies suggested that compound (<b>IIId</b>) exerts its antibacterial effect by increasing bacterial membrane permeability, reducing exopolysaccharide content, and inducing morphological alterations in bacterial cells. <i>In vitro</i> cytotoxicity assays indicated that compound (<b>IIId</b>) is essentially non-toxic to mammalian cells. <b>Conclusions:</b> Compound (<b>IIId</b>) exhibits promising potential as a lead compound for the development of more effective agricultural antibacterial agents to control <i>Xoc</i> in the future.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1529 - 1546"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145144826","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":"Molecular Species of Membrane Lipids of the Sea Anemone Exaiptasia diaphana and Its Symbionts","authors":"E. T. Bizikashvili,&nbsp;S. A. Kozlovskiy,&nbsp;E. V. Ermolenko,&nbsp;K. V. Efimova,&nbsp;T. V. Sikorskaya","doi":"10.1134/S106816202504034X","DOIUrl":"10.1134/S106816202504034X","url":null,"abstract":"<p><b>Objective:</b> The molecular species of membrane lipids of the sea anemone <i>Exaiptasia diaphana</i> and the molecular species of glycolipids of its symbionts were studied. <b>Methods:</b> Lipidomic analysis was performed using high-performance liquid chromatography with mass spectrometric detection. <b>Results and Discussion:</b> A total of 82 molecular species of <i>E. diaphana</i> glycerophospholipids were identified, the main ones being 16:0/22:6 cholineglycerophospholipid (PC), 18:1e/20:4 and 18:1e/20:5 ethanolaminglycerophospholipids (PE), 18:0/22:4 serineglycerophospholipid (PS), 18:0/22:4 inositolglycerophospholipid (PI), and 18:2b/16:0 ceramidaminoethylphosphonate (CAEP). Thirty-six molecular species of glycolipids were identified in symbionts. The main molecular species were 18:4/18:5 monogalactosyldiacylglycerol (MGDG), 18:3/18:5 and 18:4/18:4 digalactosyldiacylglycerols (DGDG), and 14:0/16:0 sulfoquinovosyldiacylglycerol (SQDG). Molecular genetic analysis revealed that all <i>E. diaphana</i> colonies contained the following dinoflagellates: <i>Breviolum minutum</i>, <i>Cladocopium thermophilum</i>, and <i>Gerakladium endoclionum</i>. <b>Conclusions:</b> The profile of lipid molecular species of the coral host can act as a chemotaxonomic feature, and galactolipids of symbionts indicate resistance to changes in seawater temperature. This study contributes to the development of lipidomics of marine organisms of the phylum Cnidaria.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1663 - 1674"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145144875","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":"Chimeric Amides of Substituted Allyl- and Phenylcarboxylic Acids with Pharmacophoric Moieties of Aromatic and Heteroaromatic Rings as Potential Multitarget Protein Kinase Inhibitors: Design, Synthesis, Evaluation of Antitumor Activity, and In Silico Analysis","authors":"E. V. Koroleva,&nbsp;Yu. V. Siniutsich,&nbsp;A. L. Ermolinskaya,&nbsp;Zh. V. Ignatovich,&nbsp;Yu. V. Kornoushenko,&nbsp;O. V. Panibrat,&nbsp;Ya. M. Katok,&nbsp;A. M. Andrianov","doi":"10.1134/S1068162025601648","DOIUrl":"10.1134/S1068162025601648","url":null,"abstract":"<p><b>Objective:</b> This study aims to synthesize and evaluate the antitumor efficacy of a series of designed chimeric amides (<b>10–14</b>, <b>16</b>, <b>19</b>, <b>21</b>, <b>25–27</b>, <b>28</b>, <b>30</b>) containing various combinations of nitrogen-based heterocycles, which are the key pharmacophores of many antitumor drugs with different mechanisms of action. <b>Methods:</b> The designed amides were synthesized and characterized using spectroscopic techniques. The antitumor activity of all these compounds against tumor cell lines K562 (chronic myeloid leukemia), HL-60 (acute promyelocytic leukemia), and HeLa (cervical carcinoma) was evaluated <i>in vitro</i> in terms of the half-maximal inhibitory concentration (IC₅₀). <b>Results and Discussion:</b> As a result, five lead compounds, amides (<b>10</b>, <b>11</b>, <b>21</b>, <b>27</b>, <b>30</b>), active against the above cell lines, were identified, followed by <i>in silico</i> analysis of their pharmacological properties and prediction of the most probable mechanism of their action against myeloid blood cells K562. <b>Conclusions:</b> In light of the data obtained, the identified compounds provide promising basic structures for the design of novel orally active antitumor agents, multitarget protein kinase inhibitors.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1734 - 1751"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145391","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":"BCR-ABL Inhibitors in the Targeted Therapy of Chronic Myeloid Leukemia","authors":"S. G. Kostryukov,&nbsp;O. A. Belyakova,&nbsp;D. V. Mishkin,&nbsp;D. V. Stulnikov,&nbsp;A. V. Dektyarev","doi":"10.1134/S106816202560031X","DOIUrl":"10.1134/S106816202560031X","url":null,"abstract":"<p>Chronic myeloid leukemia (CML) is a malignant disease of the hematopoietic system with a key pathogenic protein BCR-ABL, which seriously threatens the lives of patients. The first drug whose action is based on the inhibition of the hybrid tyrosine kinase BCR-ABL, the gene of which is located on the “Philadelphia chromosome,” was imatinib. Imatinib therapy turned out to be quite successful: patients with CML achieved a complete cytogenic response 2 years after the start of treatment and a state of stable longterm remission. However, the inevitable resistance to imatinib, which occurs in clinical settings due to mutations in the BCR-ABL kinase, gave impetus to the development of new specific drugs, such as dasatinib, nilotinib, bosutinib, and ponatinib. Currently, the pharmaceutical market offers the second and third generations of BCR-ABL tyrosine kinase inhibitors designed to combat mutant BCR-ABL and possessing better selectivity. It is noteworthy, the first allosteric inhibitor capable effectively overcome ATP binding site mutations has appeared on the market. In recent years, proteolysis-targeting chimeras (PROTAC) based on another E3 ligase ligand have been introduced, as a result they are able to overcome drug resistance through selective degradation of target proteins. Data on inhibitors that have received approved drug status for the treatment of CML are presented. Promising directions for developing novel BCR-ABL inhibitors are indicated. The relevance of this research direction is confirmed by the emergence of a significant number of new publications on this topic.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1471 - 1488"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145500","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 Carbazole-Fused Triazole Scaffolds: Evaluation of Anticancer Activity and Molecular Docking Studies","authors":"Kariyappa N. Ankali,&nbsp;B. Manjunatha,&nbsp;C. Kiran Yadav,&nbsp; Neelufar,&nbsp;Mallappa Shalavadi,&nbsp;Nagaraja Naik","doi":"10.1134/S1068162024605652","DOIUrl":"10.1134/S1068162024605652","url":null,"abstract":"<p><b>Objective:</b> The tricyclic carbazole nucleus exhibits various biological activities and is an integral part of many naturally occurring alkaloids and synthetic heterocyclic derivatives. In this work, we further explore a series of carbazole-fused triazole scaffolds. We report the synthesis and anticancer evaluation of a novel 9-((1-phenyl-1<i>H</i>-1,2,3-triazole-4-yl)methyl)-2,3-dihydro-1<i>H</i>-carbazol-4(9<i>H</i>)-one derivative rationally designed by incorporating two active pharmacophoric heterocyclic moieties, <i>viz</i>., carbazole and triazole, in one framework. <b>Methods:</b> All synthesized compounds were characterized by spectral methods, <i>viz</i>., ¹H, ¹³C NMR, and LC-MS. <i>In vitro</i> cytotoxicity of 1,2,3-triazole-linked heterocyclic fragments was investigated using the sulforhodamine B (SRB) assay against the BT474 cell line. <b>Results and Discussion:</b> All synthesized compounds possess an active 1,2,3-triazole moiety in their structure, and the carbazole nucleus has an oxo group at the 4th position. Compounds (<b>Vc–Vg</b>) displayed good anticancer activity with IC₅₀ values ranging from 15.17 to 210.9 μM against the BT474 cell line as compared to the standard drug doxorubicin, which has an IC₅₀ value of 2.32 μM. Molecular docking studies of these molecules revealed good binding interactions with their biochemical target, human epidermal growth factor receptor 2 (HER2), which acts as a networking receptor. <b>Conclusions:</b> Compounds (<b>Vc</b>), (<b>Ve</b>), and (<b>Vg</b>) showed potent cytotoxicity against the BT474 cell line, and molecular docking studies demonstrated strong binding interactions that correlated well with the experimental results.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1813 - 1823"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145144862","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, Antimicrobial, Anti-Inflammatory, Antioxidant Activities, Molecular Docking, and Dynamic Simulations with Lanosterol 14α-Demethylase of Propionyl Glucopyranoside Derivatives","authors":"J. Ferdous,&nbsp;F. Ali,&nbsp;S. Saha,&nbsp;D. Palit,&nbsp;S. M. A. Kawsar","doi":"10.1134/S1068162024606554","DOIUrl":"10.1134/S1068162024606554","url":null,"abstract":"<p><b>Objective:</b> Carbohydrate derivatives have attracted significant attention due to their broad applications in various industrial and biomedical fields. <b>Methods:</b> In this study, selective propionylation of methyl α-<i>D</i>-glucopyranoside (MDGP, <b>I</b>) was carried out, leading to the synthesis of a series of 2,3,4-tri-<i>O</i>-acyl derivatives (<b>III–VII</b>) from the 6-<i>O</i>-glucopyranoside precursor. The structures of the MDGP derivatives were confirmed by physicochemical characterization, elemental analysis, and spectral data. <i>In vitro</i> antimicrobial assays, along with the Prediction of Activity Spectra for Substances (PASS), indicated promising antifungal activity of these derivatives, which was more pronounced than their antibacterial activity. <b>Results and Discussion:</b> The compounds also exhibited notable antioxidant activity in the DPPH free radical-scavenging assay, surpassing that of the standard antioxidant. Anti-inflammatory properties were evaluated using protein denaturation assays. Supporting these findings, molecular docking studies were performed with lanosterol 14α-demethylase (CYP51A1), revealing significant binding affinities and non-covalent interactions, thereby corroborating the experimental data. The compounds met drug-likeness criteria and demonstrated favorable pharmacokinetic profiles <i>in silico</i>. Notably, compounds (<b>III</b>) and (<b>V</b>) exhibited binding affinities of −10.2 and −10.6 kcal/mol, respectively. During 100 ns molecular dynamics (MD) simulations, the RMSD, RMSF, radius of gyration, and solvent-accessible surface area (SASA) values remained within acceptable ranges. These compounds also formed a greater number of hydrogen bonds. Molecular Mechanics/Poisson–Boltzmann Surface Area (MM/PBSA) analyses of the 3-3LD6 and 5-3LD6 complexes showed that van der Waals, electrostatic, polar solvation, and SASA energy contributions positively influenced the binding free energies. <b>Conclusions:</b> Structure–activity relationship (SAR) analysis, together with <i>in vitro</i> and <i>in silico</i> studies, suggests that MDGP derivatives possess enhanced therapeutic potential and represent promising candidates for the development of new antimicrobial agents.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1675 - 1699"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145412","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, Semi-Synthesis, and Antibacterial Activities of Triterpenoid-Hydrazone Conjugates","authors":"Pengju Yang,&nbsp;Yuting Liu,&nbsp;Yunyun Zhou,&nbsp;Zhiwen Zhou,&nbsp;Yongzhong Li","doi":"10.1134/S1068162024606438","DOIUrl":"10.1134/S1068162024606438","url":null,"abstract":"<p><b>Objective:</b> To develop novel ocotillol-derived triterpenoid antibacterial agents by introducing hydrazone, acylhydrazide, and amino groups at the C-3 position, aiming to enhance their antibacterial potency, water solubility, and broaden their spectrum of activity, particularly against drug-resistant bacteria. <b>Methods:</b> Compounds (<b>VIIIa–VIIIm</b>) were synthesized <i>via</i> a multistep procedure using PPD as the starting material. The synthetic route included hydroxyl group protection, epoxidation, oxidation, and condensation with acylhydrazides. Antibacterial activity was evaluated using the broth microdilution method in LB medium against both drug-sensitive and drug-resistant bacterial strains. Cytotoxicity was assessed using the MTT assay on HEK-293, HK-2, and MCF-7 cell lines. Additional experiments included resistance development assays, bactericidal time-kill kinetics, biofilm disruption evaluation, and <i>in silico</i> prediction of pharmacokinetic properties. <b>Results and Discussion:</b> In this study, we synthesized a diverse array of hydrazone derivatives derived from ocotillol to evaluate their efficacy as antibacterial agents. The results showed that compound (<b>VIIIm</b>) exhibited exceptional potency, with minimum inhibitory concentrations (MICs) as low as 2–4 μg/mL against <i>S. aureus</i> and <i>B. subtilis</i>, and 8 μg/mL against <i>E. coli</i>. When tested against MRSA, compound (<b>VIIIm</b>) also demonstrated strong antibacterial activity, achieving an MIC of 8 μg/mL. Moreover, these hydrazone derivatives significantly enhanced the efficacy of kanamycin and chloramphenicol against MRSA and <i>E. coli</i>, as evidenced by fractional inhibitory concentration index (FICI) values below 0.5. Compound (<b>VIIIm</b>) was particularly notable for its ability to disrupt established bacterial biofilms and to delay the development of bacterial resistance compared to conventional antibiotics such as norfloxacin and colistin. Time-kill kinetics analysis provided compelling evidence that compound (<b>VIIIm</b>), at a concentration of 3 × MIC, exerted bactericidal activity against MRSA and <i>E. coli</i>. Furthermore, drug-likeness and ADME (absorption, distribution, metabolism, and excretion) predictions for the synthesized derivatives indicated overall compliance with Lipinski’s rule of five—with the exception of molecular weight—and suggested moderate oral bioavailability and intestinal absorption in humans. Mechanistic studies revealed that compound (<b>VIIIm</b>) exerted its antibacterial effect by disrupting the structural integrity of bacterial cell membranes, leading to leakage of intracellular components and subsequent cell death. <b>Conclusions:</b> <i>In vivo</i> studies supported the <i>in vitro</i> findings, demonstrating that compound (<b>VIIIm</b>) exhibited a moderate level of antibacterial efficacy in <i>S. aureus</i> infection models when administered at a dose of 80 mg/kg.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1605 - 1623"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145505","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":"C-Terminal Domain of Bacillus cereus Hemolysin II is Capable of Forming Homo- and Hetero-Oligomeric Forms of the Toxin on the Membrane Surface","authors":"O. S. Vetrova,&nbsp;N. V. Rudenko,&nbsp;B. S. Mel’nik,&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/S106816202460733X","DOIUrl":"10.1134/S106816202460733X","url":null,"abstract":"<p><b>Objective:</b> Hemolysin II (HlyII) is one of the key pathogenic factors of the opportunistic gram-positive bacterium <i>Bacillus cereus</i>. HlyII lyses target cells by forming pores on membranes. HlyII belongs to the group of β-pore-forming toxins. A distinctive feature of HlyII is the presence of a <i>C</i>-terminal domain of 94 amino acid residues (HlyIICTD). It was shown that, under slightly acidic conditions (pH 5.0) corresponding to the perimembrane region, the <i>C</i>-terminal domains, both by themselves and as part of the toxin, form stable complexes consisting of full-length and truncated toxin molecules. <b>Methods:</b> HlyII, HlyIILCTD (large <i>C</i>-terminal fragment Met225–Ile412), and HlyIICTD were obtained using recombinant producer strains <i>Escherichia coli</i> BL21(DE3). Biotinylation of HlyIICTD was carried out using <i>N</i>-hydroxysuccinimide ester of biotin. The interaction of HlyIICTD with HlyIICTD, HlyIILCTD, and HlyII, as well as that of HlyIICTD with erythrocyte membranes, were studied by enzyme-linked immunosorbent assay and immunoblotting using both horseradish peroxidase-conjugated streptavidin and monoclonal antibodies against HlyII. <b>Results and Discussion:</b> Under slightly acidic conditions, HlyIICTD interacted with both the HlyIICTD domain within the full-length toxin and with the HlyIICTD protein. The interaction of HlyIICTD with the erythrocyte membrane was enhanced several-fold in the presence of the toxin. <b>Conclusions:</b> The property of the <i>C</i>-terminal domain to form complexes with other HlyIICTDs, regardless of whether it is part of the full-length toxin, the large <i>C</i>-terminal fragment, or the short HlyIICTD under conditions corresponding to those existing near the cell membrane (pH 5.0), was revealed. The toxin in the perimembrane region exists in a partially molten-globule state, in which the <i>C</i>-terminal domains of the monomers can bind to each other, increasing the local concentration of full-length toxins.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1654 - 1662"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145506","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 Evaluation, and Molecular Docking Studies of Hexahydro-1H-xanthene-1,8(2H)-dione and 1,2,3-Triazole Hybrids as Potent Free Radical Scavengers","authors":"Jaydeep N. Lalpara,&nbsp;Bhavin B. Dhaduk,&nbsp;G. G. Dubal,&nbsp;Maneesh Kumar Gupta,&nbsp;Chandan Kumar Pashavan,&nbsp;Jayendra Kanzariya,&nbsp;Rakesh Rola,&nbsp;Mayur Shiyal,&nbsp;Sanjay D. Hadiyal","doi":"10.1134/S1068162024606013","DOIUrl":"10.1134/S1068162024606013","url":null,"abstract":"<p><b>Objective:</b> To develop and synthesize new hybrid compounds incorporating hexahydro-1<i>H</i>-xanthene-1,8(2<i>H</i>)-dione and 1,2,3-triazole with potential free radical inhibitory activity. <b>Methods:</b> The structures of all synthesized compounds were confirmed by ¹H and ¹³C NMR spectroscopy, as well as by elemental analysis. A molecular docking study was conducted for the designed compounds against the 1PRX receptor. Furthermore, the antioxidant activity of all synthesized compounds was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide (H₂O₂), and nitric oxide (NO) assays. <b>Results and Discussion:</b> A direct transformation of a xanthene-based intermediate into triazole hybrids <i>via</i> a Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction was developed, affording the desired products in 73–91% yields. <b>Conclusions:</b> Compound (<b>VIIh</b>) exhibited notable antioxidant potential compared to the reference standard.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1489 - 1497"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145289","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":"Pharmacokinetic Characteristics of Ecdystene and Ursolic Acid in Plant Extracts After Oral Administration In Vivo","authors":"D. A. Kiseleva,&nbsp;S. V. An’kov,&nbsp;T. G. Tolstikova,&nbsp;A. A. Okhina,&nbsp;A. D. Rogachev","doi":"10.1134/S1068162024607316","DOIUrl":"10.1134/S1068162024607316","url":null,"abstract":"<p><b>Objective:</b> Bioavailability determination is critically important when studying the therapeutic potential of plant extracts, as it indicates whether active compounds retain their biological activity or gradually lose efficacy under various physiological conditions. Rosemary (<i>Rosmarinus officinalis</i> L.) represents the richest source of the pentacyclic triterpenoid ursolic acid, while ecdystene (20-hydroxyecdysone) is a principal phytoecdysteroid present in Rhaponticum (<i>Rhaponticum carthamoides</i> Willd.). Both plant sources are approved for pharmaceutical distribution as dietary supplements and metabolic therapy agents. However, limited information exists regarding the pharmacokinetic profiles of ecdystene and ursolic acid in plant extracts and multicomponent formulations. This study aimed to comparatively evaluate the pharmacokinetic parameters of ecdystene, ursolic acid, Rhaponticum and Rosemary extracts, and a combination formulation containing both extracts after oral administration <i>in vivo</i>. <b>Methods:</b> Test substances and their extracts were administered as single intragastric doses to CD-1 outbred mice at doses standardized to equivalent concentrations of the primary active compounds. Ursolic acid and ecdystene concentrations in animal blood were quantified using HPLC-MS/MS for subsequent pharmacokinetic parameter calculations (<i>C</i>_max, <i>T</i>_max, AUC). <b>Results and Discussion:</b> Both compounds demonstrated decreased bioavailability in animal blood when administered as plant extracts compared to pure substances. In the combination formulation, only trace amounts of ecdystene were detected, while ursolic acid pharmacokinetic parameters showed no significant differences between the combination and rosemary extract. These findings demonstrate that combining plant extracts in multicomponent formulations can reduce bioavailability of active compounds through various physicochemical and biological mechanisms. <b>Conclusions:</b> This study confirms that plant extract combinations in multicomponent formulations may significantly decrease bioavailability of primary active substances through multiple factors. Development of plant extract-based products should incorporate comprehensive pharmacokinetic studies to ensure finished product quality and therapeutic efficacy.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1645 - 1653"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145390","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}