Russian Journal of Bioorganic Chemistry最新文献

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Improved Efficiency of OX40L-Based Gene Therapy Using a Non-Viral Delivery System in Fibroblast-Enriched Mouse Tumor Models 利用非病毒传递系统提高ox40l基因治疗富成纤维细胞小鼠肿瘤模型的效率
IF 1.7 4区 化学
Russian Journal of Bioorganic Chemistry Pub Date : 2025-09-28 DOI: 10.1134/S1068162025601430
V. V. Pleshkan, M. V. Zinovyeva, D. A. Didych, I. V. Alekseenko
{"title":"Improved Efficiency of OX40L-Based Gene Therapy Using a Non-Viral Delivery System in Fibroblast-Enriched Mouse Tumor Models","authors":"V. V. Pleshkan,&nbsp;M. V. Zinovyeva,&nbsp;D. A. Didych,&nbsp;I. V. Alekseenko","doi":"10.1134/S1068162025601430","DOIUrl":"10.1134/S1068162025601430","url":null,"abstract":"<p><b>Objective:</b> During their development, malignant tumors are able to establish a permissive microenvironment that influences their further growth and development. Cancer-associated fibroblasts play an important role in this process. However, the role of fibroblasts in therapeutic interventions remains unclear. <b>Methods:</b> We used inoculation of a co-culture of cancer cells and fibroblasts to create a cell-enriched tumor microenvironment. After tumor nodule formation, a preparation containing a plasmid encoding the gene of the ligand of the activating receptors of immune checkpoints - OX40L, controlled by the CMV promoter, was administered intratumorally. For delivery to cells, the plasmid was encapsulated in a polymer shell based on PEG-PEI-TAT. <b>Results and Discussion:</b> We evaluated the effects of fibroblasts on tumor growth and survival of mice during immunotherapy. In the proposed model, we artificially enriched the presence of fibroblasts in tumors, which to some extent can perform the function of a developed tumor microenvironment. Fibroblast-enriched tumors had an increased proliferation rate. However, with intratumoral administration of a non-viral drug encoding OX40L, we observed a significant increase in the proportion of complete responses in these tumors, reaching up to 25%. <b>Conclusions:</b> By co-inoculating cancer cells and fibroblasts, tumors with an increased proliferation rate were generated in mice. Nevertheless, some of these tumors are more likely to regress under immunotherapy than tumors composed of cancer cells alone. It is possible that the introduced fibroblasts are able to play an antigen-presenting role or act as additional sources of signals to activate the immune system.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"1927 - 1935"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1134/S1068162025601430.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synthesis, Spectral Characterization, In Vitro and In Silico Studies of Pyridinyl Pyrazole Carboxamide Derivatives 吡啶基吡唑羧酰胺衍生物的合成、光谱表征、体外和硅内研究
IF 1.7 4区 化学
Russian Journal of Bioorganic Chemistry Pub Date : 2025-09-28 DOI: 10.1134/S1068162024605044
Munusamy Sasikala, E. Revathi, Rajendran Sribalan, C. T. Ravichandran
{"title":"Synthesis, Spectral Characterization, In Vitro and In Silico Studies of Pyridinyl Pyrazole Carboxamide Derivatives","authors":"Munusamy Sasikala,&nbsp;E. Revathi,&nbsp;Rajendran Sribalan,&nbsp;C. T. Ravichandran","doi":"10.1134/S1068162024605044","DOIUrl":"10.1134/S1068162024605044","url":null,"abstract":"<p><b>Objective:</b> In pharmaceutical research, the development of medications based on small molecules is a particularly attractive area of study. This work aimed to synthesize and evaluate a new series of compounds with potential anti-inflammatory and antidiabetic activity. <b>Methods:</b> A series of small compounds containing phenyl, pyrazole, and pyridine moieties were synthesized and thoroughly characterized using mass spectrometry, FT-IR, NMR, and UV-visible spectroscopy. The compounds were subjected to <i>in vitro</i> investigations to assess their biological properties. <b>Results and Discussion:</b> The obtained results highlighted the compounds’ potential biological activity and encouraged further research, including molecular docking studies. Density Functional Theory (DFT) analysis was employed to provide a detailed explanation of the compounds’ reactivity and interactions with enzymes, offering insights into their mechanism of action. <b>Conclusions:</b> The therapeutic potential of the synthesized compounds against inflammation and diabetes was demonstrated using a combination of <i>in vitro</i> and <i>in silico</i> analyses, supporting their further development as drug candidates.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"2127 - 2141"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181448","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}
引用次数: 0
Antioxidant Profile of Anacardic Acid Derivatives and Their Effects on Oxidative Stress-Induced Diseases: An Update 心梗酸衍生物的抗氧化特性及其对氧化应激诱导疾病的影响:最新进展
IF 1.7 4区 化学
Russian Journal of Bioorganic Chemistry Pub Date : 2025-09-28 DOI: 10.1134/S1068162025600400
Priyabrata Pattanayak, Kamini Sethy
{"title":"Antioxidant Profile of Anacardic Acid Derivatives and Their Effects on Oxidative Stress-Induced Diseases: An Update","authors":"Priyabrata Pattanayak,&nbsp;Kamini Sethy","doi":"10.1134/S1068162025600400","DOIUrl":"10.1134/S1068162025600400","url":null,"abstract":"<p>Anacardic acid is the principal constituent of cashew nut shell liquid (CNSL), obtained as a byproduct in the cashew-processing industry. It represents a group of chemically related salicylic acid derivatives bearing a hydrophobic alk(en)yl side chain with varying degrees of unsaturation. Literature data indicate the antioxidant potential of anacardic acid, assessed by autoxidation assays, DPPH radical scavenging, superoxide anion generation assays, inhibition of uric acid formation by xanthine oxidase, and lipoxygenase inhibition. The available evidence suggests that the antioxidant activity of anacardic acid is primarily due to the inhibition of oxidative enzymes and suppression of superoxide anion generation, rather than direct reactive oxygen species (ROS) scavenging. Inhibition of soybean lipoxygenase-1–catalyzed linoleic acid peroxidation and the demonstrated metal-chelating ability of anacardic acid support its potential use as a preventive antioxidant in functional food formulations. Inhibition of xanthine oxidase by anacardic acid may help prevent the accumulation of uric acid, thereby reducing the risk of hyperuricemia and gout. Moreover, modulation of free radical generation and attenuation of oxidative stress by anacardic acid derivatives could contribute to protection against oxidative stress–related diseases. Finally, structure–activity relationship (SAR) studies summarized in this review provide a basis for the structural optimization of anacardic acid with the aim of designing more potent antioxidant derivatives.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"2247 - 2260"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181460","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}
引用次数: 0
Neurochemical Protection of Lutein against Sodium Nitroprusside-Induced Oxidative Damage in the Nauphoeta cinerea Model 叶黄素抗硝普钠氧化损伤的神经化学保护作用
IF 1.7 4区 化学
Russian Journal of Bioorganic Chemistry Pub Date : 2025-09-28 DOI: 10.1134/S1068162025600291
Carlos Alonso Leite dos Santos, Antonia Adeublena de Araújo Monteiro, Luiz Marivando Barros, Waseem Hassan, Jean Paul Kamdem, Abid Ali, Mashal M Almutairi, Mohammad Ibrahim
{"title":"Neurochemical Protection of Lutein against Sodium Nitroprusside-Induced Oxidative Damage in the Nauphoeta cinerea Model","authors":"Carlos Alonso Leite dos Santos,&nbsp;Antonia Adeublena de Araújo Monteiro,&nbsp;Luiz Marivando Barros,&nbsp;Waseem Hassan,&nbsp;Jean Paul Kamdem,&nbsp;Abid Ali,&nbsp;Mashal M Almutairi,&nbsp;Mohammad Ibrahim","doi":"10.1134/S1068162025600291","DOIUrl":"10.1134/S1068162025600291","url":null,"abstract":"<p><b>Objective:</b> Lutein (LTN) is a lipophilic carotenoid widely present in green leafy vegetables such as broccoli and spinach, where it plays a crucial antioxidant role. Although its protective effects against oxidative damage are well established, its interaction with compounds such as sodium nitroprusside (SNP) remains poorly understood. This study evaluated the effects of SNP, lutein, and their combination in <i>Nauphoeta cinerea</i>, aiming to determine potential protective mechanisms. <b>Methods:</b> Toxicity was assessed after 24 h of exposure using biochemical analyses and molecular docking simulations. <b>Results and Discussion:</b> Sodium nitroprusside exhibited mild toxicity, whereas lutein reduced these effects without inducing toxicity on its own. Lower doses of lutein provided significant protection, whereas higher doses caused physiological stress. The combination of lutein and SNP mitigated nitroprusside-induced toxicity and reduced iron levels in the model. <i>In silico</i> analyses indicated comparable molecular interactions for SNP and lutein, with docking simulations revealing predominant alkyl interactions with the target protein. <b>Conclusions:</b> Lutein can modulate SNP-induced toxicity in <i>Nauphoeta cinerea</i>, with protective effects at lower concentrations but potential stress at higher doses.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"2217 - 2227"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181469","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}
引用次数: 0
Cytoskeletal Regulator Zyxin Stimulates Nuclear Translocation of YAP in Xenopus laevis Embryonic Cells 细胞骨架调节剂Zyxin刺激非洲爪蟾胚胎细胞YAP的核易位
IF 1.7 4区 化学
Russian Journal of Bioorganic Chemistry Pub Date : 2025-09-28 DOI: 10.1134/S1068162025601727
E. A. Parshina, E. E. Orlov, E. E. Voronezhskaya, N. Yu. Martynova, A. G. Zaraisky
{"title":"Cytoskeletal Regulator Zyxin Stimulates Nuclear Translocation of YAP in Xenopus laevis Embryonic Cells","authors":"E. A. Parshina,&nbsp;E. E. Orlov,&nbsp;E. E. Voronezhskaya,&nbsp;N. Yu. Martynova,&nbsp;A. G. Zaraisky","doi":"10.1134/S1068162025601727","DOIUrl":"10.1134/S1068162025601727","url":null,"abstract":"<p><b>Objective:</b> This study investigates the impact of zyxin on Yes-associated protein (YAP) signaling during embryonic development of the African clawed frog, <i>Xenopus laevis</i>. Zyxin, a mechanosensitive cytoskeletal protein, modulates cellular responses to mechanical tension and plays a pivotal role in actin dynamics regulation. Its ability to translocate to the nucleus in response to altered mechanical environments makes it critical for controlling gene expression essential for cellular morphogenesis and tissue architecture. Understanding zyxinʼs interactions with signaling pathways, particularly YAP signaling, is crucial given its implications in various pathological conditions, including cancer. <b>Methods:</b> To investigate zyxinʼs regulatory role in YAP signaling, we employed morpholino oligonucleotide microinjection to generate embryonic models with reduced zyxin expression and synthetic mRNA injection to achieve zyxin overexpression. Western blot analysis was performed to measure total YAP and phosphorylated YAP (pYAP) levels in embryos at various developmental stages. Immunohistochemical analysis was used to assess YAP subcellular distribution, specifically the nuclear-to-cytoplasmic ratio. Luciferase reporter assays quantified YAP transcriptional activity in response to altered zyxin expression levels. <b>Results and Discussion:</b> Total YAP levels remained constant across developmental stages in control embryos, despite increased phosphorylated YAP levels, indicating reduced pathway activity. Zyxin knockdown resulted in decreased YAP levels at early developmental stages, while zyxin overexpression enhanced nuclear localization of YAP, suggesting that zyxin promotes YAP nuclear translocation. Luciferase assays demonstrated increased YAP transcriptional activity in zyxin-overexpressing embryos, supporting the hypothesis that zyxin enhances YAP signaling through mechanical tension modulation. <b>Conclusions:</b> These results demonstrate zyxinʼs significant role in modulating YAP signaling pathways during embryonic development. The zyxin-YAP interaction is critical for proper cell signaling and morphogenesis, revealing potential therapeutic targets for diseases associated with dysregulated cell proliferation, including cancer. Future investigations will elucidate the mechanistic basis of zyxinʼs interactions with other YAP signaling pathway components and its influence on cellular dynamics and development, advancing our understanding of cellular mechanobiology with implications for regenerative medicine and therapeutic interventions.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"1945 - 1953"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181476","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}
引用次数: 0
Synthesis of Formononetin Derivatives and Their Protective Effects Against Oxidative Stress 刺芒柄花素衍生物的合成及其对氧化应激的保护作用
IF 1.7 4区 化学
Russian Journal of Bioorganic Chemistry Pub Date : 2025-09-28 DOI: 10.1134/S1068162024607328
Zeping Luo, Liwei Pan
{"title":"Synthesis of Formononetin Derivatives and Their Protective Effects Against Oxidative Stress","authors":"Zeping Luo,&nbsp;Liwei Pan","doi":"10.1134/S1068162024607328","DOIUrl":"10.1134/S1068162024607328","url":null,"abstract":"<p><b>Objective:</b> With the molecular formula C<sub>16</sub>H<sub>12</sub>O<sub>4</sub>, formononetin (FMN) is an appealing synthon exhibiting a wide range of biological activities, including antioxidant, anti-infective, and anti-apoptotic effects. Due to increasing interest in the mechanisms of action of antioxidants, our group aimed to identify the cellular target sites of these compounds. <b>Methods:</b> Cell Counting Kit-8 (CCK-8), enzyme-linked immunosorbent assay (ELISA), transmission electron microscopy (TEM), TdT-mediated dUTP nick end labeling (TUNEL) staining, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blot were used to analyze the effects of oxidative stress on PC12 cell survival, antioxidant enzyme activity, mitochondrial morphology, apoptosis, key intracellular proteins, and signaling pathways. The potential roles of candidate targets were further investigated using proteomics, molecular docking, kinetic simulation, and cellular thermal shift assay (CETSA). <b>Results and Discussion:</b> One of the compounds, (<b>VI</b>) (5-(8-(((1-(benzyloxy)-3-hydroxy-1-oxopropan-2-yl)amino)methyl)-7-hydroxy-4-oxo-4<i>H</i>-chromen-3-yl)-2-methoxybenzenesulfonic acid), was highly active. It enhanced PC12 cell proliferation, reduced lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels, and increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, effectively inhibiting apoptosis and ameliorating mitochondrial damage. Meanwhile, (<b>VI</b>) upregulated the expression of PI3K/Akt and Nrf2/HO-1 proteins. The study also demonstrated that (<b>VI</b>) binds significantly to the oxidative stress-related protein HO-1. <b>Conclusions:</b> Compound (<b>VI</b>) effectively protects PC12 cells against H<sub>2</sub>O<sub>2</sub>-induced oxidative damage. Its protective mechanism may involve activation of the PI3K/Akt and Nrf2/HO-1 signaling pathways, with HO-1 serving as a potential key target of its action.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"2152 - 2169"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181486","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}
引用次数: 0
Synthesis, Biological Evaluation, and Computational Studies of Pyridine-Thiazolyl Hydrazones as Anticancer Candidates Targeting EGFR Kinase 靶向EGFR激酶的吡啶-噻唑基腙的合成、生物学评价和计算研究
IF 1.7 4区 化学
Russian Journal of Bioorganic Chemistry Pub Date : 2025-09-28 DOI: 10.1134/S1068162025601016
Sonali S. Shinde, Jaydeo T. Kilbile, Sachin S. Bhusari, Pravin S. Wakte
{"title":"Synthesis, Biological Evaluation, and Computational Studies of Pyridine-Thiazolyl Hydrazones as Anticancer Candidates Targeting EGFR Kinase","authors":"Sonali S. Shinde,&nbsp;Jaydeo T. Kilbile,&nbsp;Sachin S. Bhusari,&nbsp;Pravin S. Wakte","doi":"10.1134/S1068162025601016","DOIUrl":"10.1134/S1068162025601016","url":null,"abstract":"<p><b>Objective:</b> Synthesis, characterization, biological evaluation, and <i>in silico</i> studies of new 2-amino pyridine-thiazolyl hydrazones (<b>5a–5h</b>) as novel anticancer agents targeting the EGFR kinase protein. <b>Methods:</b> All designed compounds were synthesized <i>via</i> a one-pot multicomponent reaction. The synthesized compounds were evaluated for their anticancer activity against selected cancer cell lines <i>in vitro</i>, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and EGFR enzymatic assay. A computational study was conducted to explore the properties of the targeted compounds, which included drug similarity, molecular docking, and ADMET profiling. <b>Results and Discussion:</b> Among all, compounds (<b>5d</b>), (<b>5g</b>), and (<b>5h</b>) showed the most potent anticancer activity with IC<sub>50</sub> values of 9.02, 10.02, and 8.09 μM against A549, MCF-7, and DU145, respectively. Additionally, <i>in vitro</i> EGFR enzymatic activity provided insight into the anticancer mechanisms of the majority of the active molecules. Compound (<b>5d</b>) exhibited <i>in vitro</i> enzymatic inhibitory activity with an IC<sub>50</sub> value of 5.11 μM, compared to the standard osimertinib (IC<sub>50</sub> = 1.35 μM). The molecular docking study was performed against mutant EGFR (T790M/C797S) (PDB ID: 5D41) and wild-type EGFR (PDB ID: 4I23) to gain information about the interactions of the synthesized molecules with the binding pockets. The molecular docking, ADMET, and drug-likeness properties of all synthesized derivatives were computationally determined as EGFR inhibitors. <b>Conclusions:</b> Compounds (<b>5d</b>), (<b>5g</b>), and (<b>5h</b>) demonstrated significant efficacy against prostate, lung, and breast cancer cell lines. This research suggests that 2-amino pyridine-thiazolyl hydrazone molecules have the potential to be developed into effective anticancer agents in the future.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"2288 - 2303"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181499","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}
引用次数: 0
Discovery and Identification of Plant Regulatory Peptides 植物调控肽的发现与鉴定
IF 1.7 4区 化学
Russian Journal of Bioorganic Chemistry Pub Date : 2025-09-28 DOI: 10.1134/S1068162025602629
A. Yu. Skripnikov, E. E. Vorobeva, M. E. Taliansky, N. O. Kalinina
{"title":"Discovery and Identification of Plant Regulatory Peptides","authors":"A. Yu. Skripnikov,&nbsp;E. E. Vorobeva,&nbsp;M. E. Taliansky,&nbsp;N. O. Kalinina","doi":"10.1134/S1068162025602629","DOIUrl":"10.1134/S1068162025602629","url":null,"abstract":"<p>Plant regulatory peptides represent a novel class of signaling molecules that play a central role in the regulation of plant growth, development, and stress responses. Owing to high biological activity at low concentrations, they are considered promising biostimulants for environmentally sustainable agriculture. This review summarizes the key theoretical approaches and experimental methods used for the discovery and identification of plant regulatory peptides, including mass spectrometry, bioinformatics, bioassays, and <i>in silico</i> screening. An overview is provided of the major plant regulatory peptides identified to date, such as systemin, PSK, PSY, <i>At</i>Pep1, CLV3, TDIF, CEP, and CIF, along with the methods used for their isolation, chemical synthesis, and functional validation. Special attention is given to model systems based on cell cultures and seedlings, which are commonly employed to screen peptide activity, as well as to strategies for identifying their corresponding receptors. The review highlights the critical role of bioassays as a final and indispensable stage in peptide discovery pipelines, enabling the functional evaluation of both identified and putative peptides.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"1838 - 1852"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181410","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}
引用次数: 0
Unveiling the Antidiabetic Potential of 6-Chloro-3-(2-substituted-4-oxothiazolidin-3-yl)-2-phenylquinazolin-4(3H)-one Derivatives: Design, Synthesis, and Biological Evaluation Targeting Fructose 1,6-Bisphosphatase with In Silico ADMET and Docking Approaches 揭示6-氯-3-(2-取代-4-氧噻唑烷-3-基)-2-苯基喹唑啉-4(3H)- 1衍生物的抗糖尿病潜力:基于硅ADMET和对接方法靶向果糖1,6-双磷酸酶的设计、合成和生物学评价
IF 1.7 4区 化学
Russian Journal of Bioorganic Chemistry Pub Date : 2025-09-28 DOI: 10.1134/S1068162025600047
Sanjay D. Sawant, Vasundhara N. Sawant
{"title":"Unveiling the Antidiabetic Potential of 6-Chloro-3-(2-substituted-4-oxothiazolidin-3-yl)-2-phenylquinazolin-4(3H)-one Derivatives: Design, Synthesis, and Biological Evaluation Targeting Fructose 1,6-Bisphosphatase with In Silico ADMET and Docking Approaches","authors":"Sanjay D. Sawant,&nbsp;Vasundhara N. Sawant","doi":"10.1134/S1068162025600047","DOIUrl":"10.1134/S1068162025600047","url":null,"abstract":"<p><b>Objective:</b> FBPase is considered a significant player in the middle phase of the gluconeogenesis pathway and an attractive target for improving hyperglycemia in T2DM patients. To date, several FBPase inhibitors for the management of diabetes have been reported; however, many of them are structurally similar to AMP, resulting in some off-target side effects. Therefore, efforts have been made to identify novel non-AMP-mimetic FBPase inhibitors without a phosphonate moiety. <b>Methods:</b> Compounds bearing a quinazoline scaffold linked to a thiazolidinone moiety were investigated as FBPase inhibitors in this study. The synthesis, molecular docking studies, pharmacokinetic predictions, toxicity profiles, and biological activities of quinazoline–thiazolidinone derivatives are reported. <i>In silico</i> approaches were thoroughly employed to understand the binding modes at the active site of FBPase. <b>Results and Discussion:</b> The results indicated that several compounds demonstrated significant antidiabetic activity, with the highest activity observed in compound (<b>S6</b>). An in-depth examination of structural variations and their biological activities revealed that (<b>S6</b>) is the most potent compound, with an IC<sub>50</sub> value of 0.004 ± 0.10 µM. <b>Conclusions:</b> Compound (<b>S6</b>) exhibited noteworthy hypoglycemic activity and can serve as a template for the future development of FBPase inhibitors. This work also demonstrates that orally bioavailable and effective FBPase inhibitors can be developed without employing prodrug strategies.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 5","pages":"2185 - 2204"},"PeriodicalIF":1.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181453","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}
引用次数: 0
Rich Phenolic Structure of Flavone Glycosides and Feruloylquinic Acid: Evaluation of Their Bioactivity in the Natural Plant Acer palmatum var. amoenum 黄酮苷和阿魏酰奎宁酸的富酚结构:天然植物棕榈槭的生物活性评价
IF 1.7 4区 化学
Russian Journal of Bioorganic Chemistry Pub Date : 2025-09-28 DOI: 10.1134/S1068162022601161
L. Zhao, D. Jiang, C. Shen, F. Jin
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