Chemical Biology & Drug Design最新文献

筛选
英文 中文
Highly Brominated Quinolines: Synthesis, Characterization, and Investigation of Anticancer Activities Supported by Molecular Dynamics 高溴化喹啉:分子动力学支持下抗癌活性的合成、表征和研究
IF 3.2 4区 医学
Chemical Biology & Drug Design Pub Date : 2025-05-06 DOI: 10.1111/cbdd.70120
Osman Çakmak, Salih Ökten, Tuğba Kul Köprülü, Cenk A. Andac, Şaban Tekin, Seyfullah Oktay Arslan
{"title":"Highly Brominated Quinolines: Synthesis, Characterization, and Investigation of Anticancer Activities Supported by Molecular Dynamics","authors":"Osman Çakmak,&nbsp;Salih Ökten,&nbsp;Tuğba Kul Köprülü,&nbsp;Cenk A. Andac,&nbsp;Şaban Tekin,&nbsp;Seyfullah Oktay Arslan","doi":"10.1111/cbdd.70120","DOIUrl":"https://doi.org/10.1111/cbdd.70120","url":null,"abstract":"<p>In this study, we synthesized and characterized novel brominated methoxyquinolines (<b>7</b> and <b>11</b>) and nitrated bromoquinoline (<b>17</b>) derivatives with potential antiproliferative activity against cancer cell lines. Starting from 1,2,3,4-tetrahydroquinoline (THQ, <b>1</b>), a series of brominated quinoline compounds was obtained via regioselective bromination and subsequent reactions. The structure of the key compound, 3,5,6,7-tetrabromo-8-methoxyquinoline (<b>7</b>), was confirmed using 1D and 2D NMR techniques. Additionally, unexpected bromination of 3,6,8-trimethoxyquinoline (<b>5</b>) yielded 5,7-dibromo-3,6-dimethoxy-8-hydroxyquinoline (<b>11</b>), allowing functionalization of both rings in the quinoline. The direct nitration of 6,8-dibromoquinoline (<b>6</b>) yielded the corresponding 5-nitro derivative (<b>17</b>), a precursor to amino derivatives that activate the bromine group on the ring. Antiproliferative activities of these derivatives (<b>7</b>, <b>11</b>, <b>17</b>) were assessed against C6, HeLa, and HT29 cancer cell lines using the BCPE assay. Compounds <b>7</b>, <b>11</b>, and <b>17</b> exhibited significant inhibitory effects, with compound <b>11</b> showing the highest activity (IC<sub>50</sub> values of 5.45–9.6 μg/mL). Furthermore, the cytotoxicity of these compounds was evaluated using the LDH assay, indicating lower cytotoxic effects compared to the control drug 5-FU. The ability of compounds <b>11</b> and <b>17</b> to induce apoptosis was confirmed through DNA laddering, while compound <b>7</b> showed no such effect. Compounds <b>7</b> and <b>11</b> inhibited human topoisomerase I, a critical enzyme for DNA replication and repair, with significant binding energies determined by MM-PBSA studies. The wound healing assay demonstrated that compound <b>17</b> effectively inhibited the migration of HT29 cells. These findings highlight the potential of these novel quinoline derivatives as effective anticancer agents, warranting further investigation into their mechanisms of action and therapeutic applications.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Osthole Induces Hepatic Stellate Cell Ferroptosis to Alleviate Liver Fibrosis by Inhibiting the Y-Box Binding Protein 1-Wnt/β-Catenin Axis Through Downregulating Myocyte Enhancer Factor 2A 蛇床子素通过下调肌细胞增强因子2A抑制Y-Box结合蛋白1-Wnt/β-Catenin轴,诱导肝星状细胞铁凋亡减轻肝纤维化
IF 3.2 4区 医学
Chemical Biology & Drug Design Pub Date : 2025-05-03 DOI: 10.1111/cbdd.70113
Ming Tong, Meng Liu, Liang Chen, Yi-he Lin, Qing Zheng
{"title":"Osthole Induces Hepatic Stellate Cell Ferroptosis to Alleviate Liver Fibrosis by Inhibiting the Y-Box Binding Protein 1-Wnt/β-Catenin Axis Through Downregulating Myocyte Enhancer Factor 2A","authors":"Ming Tong,&nbsp;Meng Liu,&nbsp;Liang Chen,&nbsp;Yi-he Lin,&nbsp;Qing Zheng","doi":"10.1111/cbdd.70113","DOIUrl":"https://doi.org/10.1111/cbdd.70113","url":null,"abstract":"<div>\u0000 \u0000 <p>Liver fibrosis is pathologically associated with ferroptosis. Osthole (OST) has good therapeutic effects on liver fibrosis. Our study sought to investigate the pharmacological effects of OST on ferroptosis in hepatic stellate cells (HSCs) during the development of liver fibrosis and define the mechanisms involved. The in vivo model of liver fibrosis was established by CCl<sub>4</sub> treatment. MTT and EDU assays were used to assess cell viability and proliferation, respectively. The interaction between myocyte enhancer factor 2A (MEF2A) and Y-box binding protein 1 (YBX1) was analyzed by dual luciferase reporter and chromatin immunoprecipitation (ChIP) assays. OST treatment alleviated CCl<sub>4</sub>-induced liver fibrosis in mice by activating ferroptosis. OST induced ferroptosis in HSCs and inhibited the activation of HSCs in vitro, while these effects of OST were reversed by MEF2A overexpression or YBX1 overexpression. Mechanistically, MEF2A activated the Wnt/β-catenin signaling by transcriptionally facilitating YBX1 expression. As expected, the inactivation of Wnt/β-catenin signaling or YBX1 knockdown could reverse the regulatory effect of MEF2A upregulation on the activation of HSCs and ferroptosis in OST-treated HSCs. OST mitigated liver fibrosis by inducing ferroptosis in HSCs and repressing the activation of HSCs through inhibiting the MEF2A/YBX1/Wnt/β-catenin axis.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Transfer of USP25 by Exosomes of Adipose Tissue-Derived Mesenchymal Stem Cells Ameliorates Diabetic Nephropathy Through Stabilizing SMAD7 Expression 脂肪组织源性间充质干细胞外泌体转移USP25通过稳定SMAD7表达改善糖尿病肾病
IF 3.2 4区 医学
Chemical Biology & Drug Design Pub Date : 2025-05-03 DOI: 10.1111/cbdd.70118
Xinjie Wang, Siyue Huang, Xiaoqin Li, Huan Cheng
{"title":"The Transfer of USP25 by Exosomes of Adipose Tissue-Derived Mesenchymal Stem Cells Ameliorates Diabetic Nephropathy Through Stabilizing SMAD7 Expression","authors":"Xinjie Wang,&nbsp;Siyue Huang,&nbsp;Xiaoqin Li,&nbsp;Huan Cheng","doi":"10.1111/cbdd.70118","DOIUrl":"https://doi.org/10.1111/cbdd.70118","url":null,"abstract":"<div>\u0000 \u0000 <p>Adipose tissue-derived mesenchymal stem cells (ADSCs) are identified to be potential therapeutic candidates for diabetic nephropathy (DN) through secreting exosomes (Exos). Ubiquitin-specific protease 25 (USP25) has been reported to be involved in DN-induced renal injury. Herein, this study aimed to investigate whether ADSCs affected DN progression by Exo transfer of USP25. High glucose (HG)-induced mouse podocytes were used to mimic DN-induced injury for in vitro viability, inflammation, and apoptosis analyses. The db/db mice of DN were established for renal injury and function analysis in vivo. The deubiquitination effect of USP25 was analyzed by cellular ubiquitination and immunoprecipitation assays. ADSCs reversed HG-induced apoptosis and inflammation in podocytes, and these effects were achieved by Exo-mediated transfer of USP25. Mechanistically, USP25 interacted with SMAD7 protein and elevated its expression in podocytes via inducing SMAD7 deubiquitination. USP25 transferred via ADSC-Exos abolished HG-induced apoptosis and inflammation in podocytes by elevating SMAD7 protein levels. In vivo assay also confirmed that ADSC-Exo attenuated Type 2 Diabetes Mellitus-induced kidney injury and podocyte apoptosis and inflammation by releasing USP25. ADSCs attenuated T2DM-induced kidney injury, podocyte apoptosis, and inflammation via elevating SMAD7 stabilization through exosome transfer of USP25.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Computational Design of a Bicyclic Peptide Inhibitor Targeting the ICOS/ICOS-L Protein–Protein Interaction 针对ICOS/ICOS- l蛋白-蛋白相互作用的双环肽抑制剂的计算设计
IF 3.2 4区 医学
Chemical Biology & Drug Design Pub Date : 2025-05-03 DOI: 10.1111/cbdd.70117
Laura Calvo-Barreiro, Maxim Secor, Jovan Damjanovic, Somaya A. Abdel-Rahman, Yu-Shan Lin, Moustafa Gabr
{"title":"Computational Design of a Bicyclic Peptide Inhibitor Targeting the ICOS/ICOS-L Protein–Protein Interaction","authors":"Laura Calvo-Barreiro,&nbsp;Maxim Secor,&nbsp;Jovan Damjanovic,&nbsp;Somaya A. Abdel-Rahman,&nbsp;Yu-Shan Lin,&nbsp;Moustafa Gabr","doi":"10.1111/cbdd.70117","DOIUrl":"https://doi.org/10.1111/cbdd.70117","url":null,"abstract":"<div>\u0000 \u0000 <p>The interaction between the inducible T-cell costimulatory molecule (ICOS) and its ligand (ICOS-L) is a critical pathway in T-cell activation and immune regulation. We computationally designed a bicyclic peptide (CP5) that inhibits the ICOS/ICOS-L protein–protein interaction (PPI). Using the structural insights derived from the ICOS/ICOS-L co-crystal structure (PDB: 6X4G) and bias-exchange metadynamics simulations (BE-META), we first designed monocyclic peptide candidates containing the β-strand (residues 51–55 <sup>51</sup>YVYWQ<sup>55</sup>) of ICOS-L that interact with ICOS. Using Rosetta's flex ddG calculations and further disulfide-bond restraint, we arrived at CP5 (cyclo-RVY[CQPGWC]WVLpG) as a potential ICOS/ICOS-L inhibitor. Using dynamic light scattering (DLS), we examined the interaction between CP5 and ICOS. Importantly, we validated the ICOS/ICOS-L inhibitory activity of CP5 using both TR-FRET assay and ELISA. Notably, CP5 demonstrated satisfactory in vitro pharmacokinetic properties, such as metabolic stability and lipophilicity, positioning it as a promising candidate for further drug development. Our findings provide a foundation for future drug discovery efforts aiming to develop cyclic peptides that specifically target the ICOS/ICOS-L interaction.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Network Pharmacology Integrated Experimental Validation Uncover Quercetin as the Key Ingredient of Hedyotis diffusa Anti-BRCA 网络药理学综合实验验证揭示槲皮素是白花蛇舌草抗brca的关键成分
IF 3.2 4区 医学
Chemical Biology & Drug Design Pub Date : 2025-04-25 DOI: 10.1111/cbdd.70112
Queting Chen, Yuanzhuang Xu, Jianhua Ma, Gaotao Zhang, Zhengyu Yin, Donghao Zhang, Duqiang Luo, Zhiqin Liu
{"title":"Network Pharmacology Integrated Experimental Validation Uncover Quercetin as the Key Ingredient of Hedyotis diffusa Anti-BRCA","authors":"Queting Chen,&nbsp;Yuanzhuang Xu,&nbsp;Jianhua Ma,&nbsp;Gaotao Zhang,&nbsp;Zhengyu Yin,&nbsp;Donghao Zhang,&nbsp;Duqiang Luo,&nbsp;Zhiqin Liu","doi":"10.1111/cbdd.70112","DOIUrl":"https://doi.org/10.1111/cbdd.70112","url":null,"abstract":"<div>\u0000 \u0000 <p><i>Hedyotis diffusa</i>, a famous Traditional Chinese Medicine (TCM), has been extensively used clinically for thousands of years. Although the therapeutic effect of <i>Hedyotis diffusa</i> on tumors has attracted wide attention, components, and mechanisms against breast cancer (BRCA) have not been fully understood. The study aims to explore the active components and molecular mechanisms of <i>Hedyotis diffusa</i> against BRCA using network pharmacology combined with experimental validation. The results of network pharmacology indicated that quercetin was the most core component of <i>Hedyotis diffusa</i>. BIRC5, CDK1, FOS, and HSP90AA1 were considered candidate key targets of <i>Hedyotis diffusa</i> against BRCA. KEGG enrichment analysis revealed that multiple cancer-related pathways are enriched, including pathways in cancer, estrogen signaling pathway, and PI3K-AKT signaling pathway, and the like. The results of in vitro experiments showed that quercetin inhibited the proliferation of both MCF-7 cells and MDA-MB-231 cells in a dose-dependent manner. Furthermore, the experimental data demonstrated quercetin may decrease the expression level of BIRC5, CDK1, and HSP90AA1 in MCF-7 cells. Overall, results of the study indicated that quercetin may play a vital role in the anti-BRCA effect of <i>Hedyotis diffusa</i>, and quercetin can affect the expression of BIRC5, CDK1, and HSP90AA1 in MCF-7 cells. This study may provide new evidence for the use of <i>Hedyotis diffusa</i> in the treatment of BRCA.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to “Protocatechuic Acid Alleviates Inflammation and Oxidative Stress in Acute Respiratory Distress Syndrome by Promoting Unconventional Prefoldin RPB5 Interactor 1-Mediated Mitophagy” 更正“原儿茶酸通过促进非常规前折叠蛋白RPB5相互作用因子1介导的线粒体自噬,减轻急性呼吸窘迫综合征的炎症和氧化应激”
IF 3.2 4区 医学
Chemical Biology & Drug Design Pub Date : 2025-04-21 DOI: 10.1111/cbdd.70109
{"title":"Correction to “Protocatechuic Acid Alleviates Inflammation and Oxidative Stress in Acute Respiratory Distress Syndrome by Promoting Unconventional Prefoldin RPB5 Interactor 1-Mediated Mitophagy”","authors":"","doi":"10.1111/cbdd.70109","DOIUrl":"https://doi.org/10.1111/cbdd.70109","url":null,"abstract":"<p>\u0000 <span>Li, X</span>, <span>Gu, Q</span>, <span>Xu, J</span>, <span>Liu, B</span>, <span>Luo, P</span>, <span>Zhao, M</span>. <span>Protocatechuic Acid Alleviates Inflammation and Oxidative Stress in Acute Respiratory Distress Syndrome by Promoting Unconventional Prefoldin RPB5 Interactor 1-Mediated Mitophagy</span>. <i>Chem Biol Drug Des.</i> <span>2025</span>; <span>105</span>(<span>3</span>):e70072. https://doi.org/10.1111/cbdd.70072.\u0000 </p><p>For the quantitative histograms of WBC in BALF (Figures 3B and 4C), the values are inaccurate due to our inadvertent omission of some types of WBC. We need to make an erratum to this, which does not affect the conclusions of the article. The correct figures are provided below:</p><p>We apologize for this error.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bioinformatic Analysis of the Protective Effects of Dexmedetomidine and Thrombopoietin Against Hypoxia/Reoxygenation-Induced Injury in AC16 Cells 右美托咪定和血小板生成素对缺氧/再氧损伤AC16细胞保护作用的生物信息学分析
IF 3.2 4区 医学
Chemical Biology & Drug Design Pub Date : 2025-04-19 DOI: 10.1111/cbdd.70105
Cuiyan Xing, Mingyi Wu, Xiaoyang Zhou, Benhang Gong
{"title":"Bioinformatic Analysis of the Protective Effects of Dexmedetomidine and Thrombopoietin Against Hypoxia/Reoxygenation-Induced Injury in AC16 Cells","authors":"Cuiyan Xing,&nbsp;Mingyi Wu,&nbsp;Xiaoyang Zhou,&nbsp;Benhang Gong","doi":"10.1111/cbdd.70105","DOIUrl":"https://doi.org/10.1111/cbdd.70105","url":null,"abstract":"<p>This study aimed to investigate the protective mechanisms of dexmedetomidine (Dex) and thrombopoietin (TPO) against hypoxia/reoxygenation (H/R)-induced myocardial injury. Human cardiomyocyte AC16 cells were subjected to hypoxic conditions and treated with Dex and TPO. Cellular responses, including proliferation, apoptosis, and autophagy, were assessed. RNA sequencing and bioinformatic analyses were conducted to identify differentially expressed genes, followed by functional pathway enrichment analysis. The results demonstrated that Dex and TPO significantly promoted cell proliferation, reduced apoptosis and autophagy, and inhibited caspase-3 activity and light chain 3B (LC3B) expression. Pathway enrichment analysis revealed the involvement of mitogen-activated protein kinase (MAPK), transforming growth factor beta (TGF-β), and tumor necrosis factor (TNF) signaling pathways. Although both treatments demonstrated overlapping effects, they also exhibited distinct gene regulation mechanisms. These findings suggested that Dex and TPO could mitigate H/R-induced myocardial injury through complex gene regulatory mechanisms, highlighting their potential as therapeutic strategies for myocardial ischemia–reperfusion injury (MIRI).</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Berberine Ameliorates Pulmonary Fibrosis by Inactivating the Thrombospondin 2/Smad Homolog 2/3 Pathway 小檗碱通过灭活血小板反应蛋白2/Smad同源物2/3通路改善肺纤维化
IF 3.2 4区 医学
Chemical Biology & Drug Design Pub Date : 2025-04-18 DOI: 10.1111/cbdd.70111
Liwen Zhang, Jie Chen, Xiang Huang, Yucheng Zhang, Di Wu, Wenqian Zhu
{"title":"Berberine Ameliorates Pulmonary Fibrosis by Inactivating the Thrombospondin 2/Smad Homolog 2/3 Pathway","authors":"Liwen Zhang,&nbsp;Jie Chen,&nbsp;Xiang Huang,&nbsp;Yucheng Zhang,&nbsp;Di Wu,&nbsp;Wenqian Zhu","doi":"10.1111/cbdd.70111","DOIUrl":"https://doi.org/10.1111/cbdd.70111","url":null,"abstract":"<div>\u0000 \u0000 <p>Pulmonary fibrosis (PF) is a progressive and irreversible lung disease. Previous studies have shown that berberine (BBR) ameliorates PF; however, the mechanism of BBR regulating PF remains unclear. mRNA expression of thrombospondin 2 (THBS2) was analyzed by quantitative real-time polymerase chain reaction. Protein expression level was detected by western blotting assay or immunohistochemistry assay. Cell function was analyzed using cell counting kit-8 assay, 5Ethynyl-2'-deoxyuridine assay, transwell invasion assay, wound-healing assay, enzyme-linked immunosorbent assays, and colorimetric assay. PF mouse model was established using bleomycin (BLM) to analyze the effect of BBR on PF. The results showed that THBS2 expression was upregulated in the lung tissues of BLM-induced PF mice and transforming growth factor-β1 (TGF-β1)-induced HLF cells. BBR ameliorated BLM-induced PF in vivo. TGF-β1 treatment induced HLF cell proliferation, invasion, migration, inflammation response, and oxidative stress, accompanied by increases in collagen I, fibronectin, and α-SMA protein expression; however, these effects were attenuated after THBS2 silencing. In addition, BBR attenuated TGF-β1-induced pro-fibrotic phenotypes of HLF cells and BLM-induced PF through the inactivation of the THBS2/Smad2/3 pathway. Thus, BBR inhibited BLM-induced PF by inactivating the THBS2/Smad2/3 pathway, providing a theoretical basis for PF treatment with BBR.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Quercetin Prevents Hyperuricemia Associated With Gouty Arthritis by Inactivating the NLRP3/NF-κB Signaling Pathway 槲皮素通过抑制 NLRP3/NF-κB 信号通路预防痛风性关节炎相关的高尿酸血症
IF 3.2 4区 医学
Chemical Biology & Drug Design Pub Date : 2025-04-15 DOI: 10.1111/cbdd.70103
Qingliang Meng, Chenyang Song, Junfu Ma, Jiakang Cui, Junping Zhan, Jing Zhao, Yunan Zhang, Zelin Zhu, Xuzhao Du
{"title":"Quercetin Prevents Hyperuricemia Associated With Gouty Arthritis by Inactivating the NLRP3/NF-κB Signaling Pathway","authors":"Qingliang Meng,&nbsp;Chenyang Song,&nbsp;Junfu Ma,&nbsp;Jiakang Cui,&nbsp;Junping Zhan,&nbsp;Jing Zhao,&nbsp;Yunan Zhang,&nbsp;Zelin Zhu,&nbsp;Xuzhao Du","doi":"10.1111/cbdd.70103","DOIUrl":"https://doi.org/10.1111/cbdd.70103","url":null,"abstract":"<div>\u0000 \u0000 <p>Quercetin (QCT) shows great therapeutic potential for hyperuricemia (HUA) associated with gouty arthritis (GA). However, the underlying mechanism of QCT in inhibiting the progression of HUA and GA remains unclear. HUA mouse model was established by injection of oteracil potassium (OXO) combined with ethambutol (EMB). The GA mouse model was established by intraarticular injection of sodium urate (MSU). MSU-induced HK-2 cells as well as lipopolysaccharide (LPS) and MSU-induced THP-1/M0 macrophages were used as cell models. The ankle perimeter of each mouse was measured to evaluate ankle swelling. The study also detected serum levels of uric acid (UA), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β (IL-1β), and IL-6 and analyzed the pathological conditions of synovial tissues and renal tissues. QCT treatment inhibited ankle joint swelling, TNF-α, IL-1β, and IL-6 serum levels as well as UA production in HUA and GA mice. Treatment with QCT inhibited oxidative stress in the renal tissues of HUA and GA mice and MSU-induced HK-2 cells. QCT treatment inhibited the inflammatory response in LPS and MSU-induced THP-1/M0 macrophages. QCT treatment inactivated the NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/nuclear factor kappa-B (NF-κB) pathway. QCT inactivated the NLRP3/NF-κB signaling pathway to prevent HUA associated with GA.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Natural Pangenotypic Hepatitis C Virus Preventives- a Hope With Terfenadine 天然的泛型丙型肝炎病毒预防-特非那定的希望
IF 3.2 4区 医学
Chemical Biology & Drug Design Pub Date : 2025-04-15 DOI: 10.1111/cbdd.70107
Maitri Singh, Dwaipayan Chaudhuri, M. D. Irfan, Kalyan Giri, Aparna Mukhopadhyay
{"title":"Natural Pangenotypic Hepatitis C Virus Preventives- a Hope With Terfenadine","authors":"Maitri Singh,&nbsp;Dwaipayan Chaudhuri,&nbsp;M. D. Irfan,&nbsp;Kalyan Giri,&nbsp;Aparna Mukhopadhyay","doi":"10.1111/cbdd.70107","DOIUrl":"https://doi.org/10.1111/cbdd.70107","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatitis C viral infections are a leading cause of long-term liver disease and hepatocellular cancer in drug addicts and other at-risk people, including those who require frequent blood transfusions. Current drug treatments are expensive and have numerous side effects; hence, more affordable treatment plans are required. Furthermore, there are not any preventives in the market. HCV comes in 8 genotypes, and the prevalence of genotypes varies worldwide. Hence, affordable, pangenotypic preventives are needed. In this study, we selected 83 natural compounds that have been shown to have anti-HCV properties. <i>In silico</i> screening was done via docking assays to check whether any of these compounds could potentially bind to the receptor interaction site of surface protein-E2 of genotypes 1a, 1b, 2a, 3a, and 3b. From the binding energies, five compounds were selected that exhibited pangenotypic effects. MD simulation was conducted on these compounds to assess their interaction properties. ADME properties and further drug likeliness revealed one of the compounds, Terfenadine, to be similar to an anti-allergy drug, Fexofenadine. To assess in vitro validation, a binding assay was set up using E2-GFP expressed in HEK293T cells with the primary receptor CD81. It was observed that Terfenadine (used as the derivative Fexofenadine) could inhibit an interaction between CD81 and E2. We conclude that there is potential for Terfenadine/fexofenadine to be effective as a preventive against the HCV genotypes 1a, 1b, 2a, 3a, and 3b. Further clinical validation is required to confirm these findings.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信