Chemical Biology & Drug Design最新文献_第3页

Correction to “Targeting the Autophagy–Apoptosis Axis in Osteosarcoma: Therapeutic Potential of Biocompounds: A Review” 对“靶向骨肉瘤的自噬-凋亡轴：生物化合物的治疗潜力：综述”的更正。

IF 3.3 4区医学

Chemical Biology & Drug Design Pub Date : 2026-02-23 DOI: 10.1111/cbdd.70273

引用次数: 0

Coumarin-Augmented Thiazole Hybrids as Dual Anticancer and Antibacterial Agents 香豆素增强噻唑复合物作为抗癌和抗菌的双重作用。

IF 3.3 4区医学

Chemical Biology & Drug Design Pub Date : 2026-02-20 DOI: 10.1111/cbdd.70261

Islam K. Matar, Magdi E. A. Zaki, Zeinab A. Muhammad, Dahlia A. Awwad, Sami A. Al-Hussain, Chérif F. Matta, Refaie M. Kassab

{"title":"Coumarin-Augmented Thiazole Hybrids as Dual Anticancer and Antibacterial Agents","authors":"Islam K. Matar, Magdi E. A. Zaki, Zeinab A. Muhammad, Dahlia A. Awwad, Sami A. Al-Hussain, Chérif F. Matta, Refaie M. Kassab","doi":"10.1111/cbdd.70261","DOIUrl":"10.1111/cbdd.70261","url":null,"abstract":"Coumarins are a privileged scaffold in medicinal chemistry, renowned for diverse therapeutic activities including antiviral, anticancer, and neuroprotective effects. Building on our previous work with 3-substituted coumarins as inhibitors of tumor-associated carbonic anhydrases, we report a novel series of thiazol-hydrazono-coumarins targeting the ATP-binding domain of topoisomerase enzymes. Seventeen compounds were synthesized and evaluated for selective cytotoxicity against HeLa cells versus WI-38 fibroblasts and for antimicrobial activity against four ESKAPE pathogens, Escherichia coli, and Salmonella typhimurium. Several derivatives showed potent antibacterial activity, with MICs as low as 0.12 μg/mL against resistant Staphylococcus aureus strains and inhibition zones up to 33 mm against Gram-negative bacteria. Compound 13 exhibited strong selectivity, with an IC50 of 26.8 μg/mL in HeLa cells and 220.7 μg/mL in WI-38 cells. The five most active compounds were studied via molecular docking and MM/GBSA to elucidate their binding to bacterial DNA gyrase, topoisomerase IV, and human topoisomerase IIα. A molecular dynamics simulation of the S. aureus DNA gyrase B-compound 13 complex revealed a novel hydrogen bond between the coumarin ring and serine-129. These findings highlight thiazol-hydrazono-coumarins as promising antibacterial leads with ancillary anticancer activity, supporting their potential in treating infections in immunocompromised cancer patients.","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12923669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260426","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

New Non-Saccharide Heparin Mimetics as Inhibitors of Cathepsin G 新的非糖肝素模拟物作为组织蛋白酶G的抑制剂。

IF 3.3 4区医学

Chemical Biology & Drug Design Pub Date : 2026-02-18 DOI: 10.1111/cbdd.70271

Daniel K. Afosah, Madhusoodanan Mottamal, Srabani Kar, Emily Lauren Schenk Smith, Alexandra C. Selico-Dunn, Syed A. Ahmed, Rami A. Al-Horani

{"title":"New Non-Saccharide Heparin Mimetics as Inhibitors of Cathepsin G","authors":"Daniel K. Afosah, Madhusoodanan Mottamal, Srabani Kar, Emily Lauren Schenk Smith, Alexandra C. Selico-Dunn, Syed A. Ahmed, Rami A. Al-Horani","doi":"10.1111/cbdd.70271","DOIUrl":"10.1111/cbdd.70271","url":null,"abstract":"<div>\u0000 \u0000 Cathepsin G (CatG), a neutrophil serine protease, plays several roles in host defense, inflammation, and vascular pathology. Selective inhibition of CatG is therefore a compelling therapeutic strategy, yet existing inhibitors such as sulfated saccharides are limited by structural heterogeneity, instability, and bleeding risk. In this study, sulfonated non-saccharide heparin mimetics were explored as a new class of CatG inhibitors with improved stability and drug-like properties. A focused library of derivatives was screened, and several candidates demonstrated potent inhibition, with the most active compound (inhibitor 7) achieving complete CatG inhibition at nanomolar concentrations (IC50 = 86 nM). Inhibitor 7 exhibited remarkable selectivity over clotting factors, digestive enzymes, and related proteases, effectively protected extracellular matrix proteins from CatG-mediated degradation, and neither prolonged plasma clotting times nor induced cytotoxicity at tested levels. Mechanistic studies revealed an allosteric mode of action, whereby inhibitor 7 bound to a distinct anion-binding site on CatG, inducing local conformational changes that disrupted catalysis without affecting substrate recognition. Structural advantages of sulfonated scaffolds, including chemical stability, resistance to enzymatic cleavage, and synthetic accessibility, make them better than sulfated mimetics for long-term development. These findings identify sulfonated heparin mimetics, particularly inhibitor 7, as promising allosteric inhibitors of CatG with potential for safe and selective therapeutic application in vascular and inflammatory disorders.\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222367","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

Fragment-Based Design of Pseudo-Natural Products, Synthesis, and Evaluation of Their HIV-1 Latency-Reversing Properties 基于片段的伪天然产物设计、合成及其HIV-1延迟逆转特性的评价。

IF 3.3 4区医学

Chemical Biology & Drug Design Pub Date : 2026-02-17 DOI: 10.1111/cbdd.70235

Solange A. Tanyi, Donatus B. Eni, Mohamed Abdelsalam, Mathieu J. M. Tjegbe, Matthias Schmidt, Roland N. Ndip, Ian Tietjen, Wolfgang Sippl, Fidele Ntie-Kang

{"title":"Fragment-Based Design of Pseudo-Natural Products, Synthesis, and Evaluation of Their HIV-1 Latency-Reversing Properties","authors":"Solange A. Tanyi, Donatus B. Eni, Mohamed Abdelsalam, Mathieu J. M. Tjegbe, Matthias Schmidt, Roland N. Ndip, Ian Tietjen, Wolfgang Sippl, Fidele Ntie-Kang","doi":"10.1111/cbdd.70235","DOIUrl":"10.1111/cbdd.70235","url":null,"abstract":"<div>\u0000 \u0000 The goal of this project is to design, synthesize, and test compounds that combine fragments derived from natural products (NPs) for their HIV-1 latency-reversal properties, particularly those that act by histone deacetylase inhibition. A fragment library was created by implementing the Retrosynthetic Combinatorial Analysis Procedure (RECAP) on a collection of NPs isolated from different regions in Africa. The top-scoring docked fragments within the histone deacetylase (HDAC1) binding site were reconstructed to design and synthesize chemical scaffolds that have not been previously described as HDAC inhibitors. Synthesized compounds were then tested for the ability to reverse HIV latency in J-Lat 10.6 cells and/or inhibit cellular histone deacetylases. The synthesized scaffolds include indole-chalcones and aminobenzamides. Of fifty-one synthesized compounds, compound S2-13 was the most active with HIV latency reversal 20.2% ± 6.2% of J-Lat 10.6 cells at 10 μg/mL (25.1 μM), which was comparable to the HIV latency-reversing agent Prostratin. S2-13 also inhibited HDAC activity with a half-maximal inhibitory concentration (IC50) of 17.0 μM. We demonstrate that the use of pseudo-NPs can identify novel chemical scaffolds that can reverse HIV latency and inhibit HDACs in vitro.\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215454","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

Assessment of Antidiarrheal Activity of Fraxin in Chick: Synergistic Effects and Molecular Docking Study 卵黄素对鸡止泻作用的评价：协同效应及分子对接研究。

IF 3.3 4区医学

Chemical Biology & Drug Design Pub Date : 2026-02-17 DOI: 10.1111/cbdd.70266

Wahidul Alam, Salehin Sheikh, Raihan Chowdhury, Md. Sakib Al Hasan, Tanzila Akter Eity, Md. Shimul Bhuia, Most. Israt Jahan Oni, Siddique Akber Ansari, Nowreen Tabassum Ahammed, Hossam Kamli, Sarfaraz Ahmed, Muhammad Torequl Islam

{"title":"Assessment of Antidiarrheal Activity of Fraxin in Chick: Synergistic Effects and Molecular Docking Study","authors":"Wahidul Alam, Salehin Sheikh, Raihan Chowdhury, Md. Sakib Al Hasan, Tanzila Akter Eity, Md. Shimul Bhuia, Most. Israt Jahan Oni, Siddique Akber Ansari, Nowreen Tabassum Ahammed, Hossam Kamli, Sarfaraz Ahmed, Muhammad Torequl Islam","doi":"10.1111/cbdd.70266","DOIUrl":"10.1111/cbdd.70266","url":null,"abstract":"<div>\u0000 \u0000 Fraxin (FRX), a natural compound, has gained attention for its potential therapeutic effects, particularly in gastrointestinal disorders. This study investigates the antidiarrheal activity of FRX in both in vivo and in silico models. In the in vivo study, chicks received FRX (5 and 10 mg/kg) alongside bismuth subsalicylate (BSS) and loperamide (LOP) as standards, assessing antidiarrheal efficacy in castor oil and magnesium sulfate-induced diarrhea models, while the in silico study examined compounds targeting COX-2 and MOR receptors. FRX (5 and 10 mg/kg) significantly (p < 0.05) delayed latency and reduced diarrheal secretion in both castor oil and magnesium sulfate-induced diarrhea models, with inhibition of up to 42.55% and 38.89%, respectively. Combination therapies (BSS-5 + FRX-5), (BSS-10 + FRX-10), and (LOP-3 + FRX-10) significantly (p < 0.05) enhanced efficacy, with up to 74.47% and 75.93% inhibition, compared to individual treatments and control. In silico studies showed that FRX has a strong binding affinity for COX-2 (−8.8 kcal/mol) and MOR (−7.1 kcal/mol) receptors. Toxicity prediction indicated lower toxicity (Class 5, LD50: 5000 mg/kg), and no signs of hepatotoxicity or neurotoxicity were observed. These findings suggest that FRX possesses strong antidiarrheal properties, likely mediated through COX-2 and MOR interactions, and may serve as a promising therapeutic agent for inflammation-related conditions in the near future.\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215484","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

Paeoniflorin Ameliorates Osteoarthritis via Ring Finger Protein 216/Optineurin-Mediated Autophagy Activation in Chondrocytes 芍药苷通过环指蛋白216/视神经蛋白介导的软骨细胞自噬激活改善骨关节炎。

IF 3.3 4区医学

Chemical Biology & Drug Design Pub Date : 2026-02-16 DOI: 10.1111/cbdd.70237

Cheng Peng, Ding Jiang, Ningyang Gao, Yuxin Zheng, Haitao Xu

{"title":"Paeoniflorin Ameliorates Osteoarthritis via Ring Finger Protein 216/Optineurin-Mediated Autophagy Activation in Chondrocytes","authors":"Cheng Peng, Ding Jiang, Ningyang Gao, Yuxin Zheng, Haitao Xu","doi":"10.1111/cbdd.70237","DOIUrl":"10.1111/cbdd.70237","url":null,"abstract":"<div>\u0000 \u0000 Osteoarthritis (OA) is a prevalent degenerative joint disorder. Paeoniflorin (PF), a primary bioactive compound from Paeonia lactiflora roots, demonstrates therapeutic potential for OA. This study investigated the effects and mechanisms of PF in OA. In vitro, an OA model was established using interleukin-1β (IL-1β)-treated chondrocytes. In vivo, an OA mouse model was generated via destabilization of the medial meniscus (DMM). Molecular docking, bioinformatics analysis, and experimental validation identified ring finger protein 216 (RNF216) as a PF target. RNF216 overexpression and optineurin (OPTN) overexpression were achieved via genetic manipulation. Autophagy was evaluated by Western blot, transmission electron microscopy, and monomeric red fluorescent protein (mRFP)-green fluorescent protein (GFP)-microtubule-associated protein 1A/1B-light chain 3 (LC3) reporter. PF attenuated chondrocyte injury in vitro and alleviated OA progression in vivo. Through molecular docking and cellular thermal shift assay (CETSA), we identified carbonic anhydrase IX (CAIX, CA9) as a direct target of PF. RNF216 overexpression abolished PF's chondroprotective effects, which were rescued by OPTN overexpression. The autophagy inhibitor 3-methyladenine (3-MA) blocked PF-mediated chondroprotection via the RNF216/OPTN axis. Mechanistically, PF inhibited RNF216-dependent ubiquitination and degradation of OPTN, enhancing autophagic flux to mitigate cartilage damage. PF alleviates OA by suppressing RNF216-mediated OPTN ubiquitination, stabilizing OPTN to activate autophagy and protect chondrocytes. These findings highlight PF as a promising therapeutic agent for OA.\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146207103","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

Curculigoside Induces Ferroptosis in Non-Small Cell Lung Cancer Cells Through a Mechanism Involving Wilms' Tumor 1-Associating Protein-Mediated m6A Modification of GTP Cyclohydrolase 1 通过Wilms' Tumor 1- associated protein介导m6A修饰GTP环水解酶1的机制，莪术皂苷诱导非小细胞肺癌细胞铁凋亡

IF 3.3 4区医学

Chemical Biology & Drug Design Pub Date : 2026-02-16 DOI: 10.1111/cbdd.70263

Lizheng Lv, Pingyan Jin, Jiaqi Cheng, Yingying Zhang

{"title":"Curculigoside Induces Ferroptosis in Non-Small Cell Lung Cancer Cells Through a Mechanism Involving Wilms' Tumor 1-Associating Protein-Mediated m6A Modification of GTP Cyclohydrolase 1","authors":"Lizheng Lv, Pingyan Jin, Jiaqi Cheng, Yingying Zhang","doi":"10.1111/cbdd.70263","DOIUrl":"10.1111/cbdd.70263","url":null,"abstract":"<div>\u0000 \u0000 Ferroptosis plays a critical role in non-small cell lung cancer (NSCLC) progression. Curculigoside (Cur) exhibits anti-cancer properties. This study aimed to elucidate the precise action of Cur on NSCLC ferroptosis. Various concentrations of Cur were used to treat A549 and H520 cells to evaluate its cytotoxicity. The regulation of Wilms' tumor 1-associating protein (WTAP) on GTP cyclohydrolase 1 (GCH1) was verified by methylated RNA immunoprecipitation (MeRIP) and mRNA stability assays. Cur suppressed proliferative, migratory, and invasive capacities of A549 and H520 cells in vitro and reduced tumor growth in A549-derived subcutaneous xenografts in vivo. Cur induced ferroptosis in A549 and H520 cells. Mechanistically, Cur decreased the protein levels of GCH1 and WTAP, and WTAP mediated the N6-methyladenosine (m6A) methylation and stabilization of GCH1 mRNA. GCH1 depletion promoted NSCLC cell ferroptosis and impeded their malignant phenotypes. Moreover, overexpression of GCH1 reversed Cur-induced ferroptosis and malignant phenotype inhibition in A549 and H520 NSCLC cells. Our study suggested that Cur induced ferroptosis and suppressed malignant phenotypes in NSCLC in part through the WTAP-GCH1 axis, thereby revealing a novel mechanism for its therapeutic potential.\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146208504","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

Integrated Experimental and Computational Investigation of 7-Bromoochromone Thiosemicarbazones as α-Glucosidase Inhibitors 7-溴色酮硫代氨基脲类α-葡萄糖苷酶抑制剂的综合实验与计算研究。

IF 3.3 4区医学

Chemical Biology & Drug Design Pub Date : 2026-02-13 DOI: 10.1111/cbdd.70267

Eshah Shahzadi, Uzma Ghaffar, Ajmal Khan, Mariya al-Rashida, Mostafa A. Ismail, Talha Islam, Eiman Ejaz, Rima D. Alharthy, Ahmed Al-Harrasi, Sobhi M. Gomha, Zahid Shafiq

{"title":"Integrated Experimental and Computational Investigation of 7-Bromoochromone Thiosemicarbazones as α-Glucosidase Inhibitors","authors":"Eshah Shahzadi, Uzma Ghaffar, Ajmal Khan, Mariya al-Rashida, Mostafa A. Ismail, Talha Islam, Eiman Ejaz, Rima D. Alharthy, Ahmed Al-Harrasi, Sobhi M. Gomha, Zahid Shafiq","doi":"10.1111/cbdd.70267","DOIUrl":"10.1111/cbdd.70267","url":null,"abstract":"<div>\u0000 \u0000 Diabetes mellitus (DM) is a metabolic condition commonly marked by increased blood glucose levels and effectively managed with α-glucosidase inhibitors. In this study, a novel series of 7-bromochromone-based thiosemicarbazones 4(a-r) was synthesized and assessed for their α-glucosidase inhibition. All the compounds demonstrated excellent inhibitory potential with IC50 values in the range of 97.87 ± 0.01 μM—353.34 ± 0.06 μM, vastly outperforming the standard inhibitor acarbose (IC50 = 871.40 ± 1.24 μM). Compound 4h, bearing a 2,3-dichlorophenyl substituent, showed the highest potency (97.87 ± 0.01 μM). Molecular docking and molecular dynamics (MD) simulations were conducted to investigate the binding interactions of these compounds within the α-glucosidase active site. Among the synthesized compounds, 4h demonstrated the most favorable docking configuration and stable binding interactions, suggesting its potential as a lead candidate in the development of novel antidiabetic agents.\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146183908","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

Novel Hexahydropyrimidine Derivatives as Potential Neutral Sphingomyelinase 2 Inhibitors: Synthesis, Metal Chelation, and In Silico Studies 新型六氢嘧啶衍生物作为潜在的中性鞘磷脂酶2抑制剂：合成、金属螯合和硅研究。

IF 3.3 4区医学

Chemical Biology & Drug Design Pub Date : 2026-02-09 DOI: 10.1111/cbdd.70245

Ozge Kuyrukcu Ozturk, Yasemin Dundar

{"title":"Novel Hexahydropyrimidine Derivatives as Potential Neutral Sphingomyelinase 2 Inhibitors: Synthesis, Metal Chelation, and In Silico Studies","authors":"Ozge Kuyrukcu Ozturk, Yasemin Dundar","doi":"10.1111/cbdd.70245","DOIUrl":"10.1111/cbdd.70245","url":null,"abstract":"<div>\u0000 \u0000 Neutral sphingomyelinase 2 (nSMase2) plays a pivotal role in exosome biogenesis and the progression of several neurodegenerative disorders and cancers. In this study, a series of hexahydropyrimidine and tetrahydropyrimidine derivatives were synthesized to explore their potential as nSMase2 inhibitors. The compounds were evaluated for Bacillus cereus SMase inhibition, which shares a highly conserved substrate-binding site with human nSMase2. The hexahydropyrimidine derivatives exhibited superior activity, with 4-(4-fluorophenyl)-6-oxo-2-thioxohexahydropyrimidine-5-carbonitrile (compound 1j, IC50 = 1.88 μM) emerging as the most potent inhibitor fourfold more active than the reference compound Cambinol (IC50 = 7.49 μM). Compound 1j also demonstrated metal-chelating ability with Fe3+ and Cu2+ ions, which are implicated in the pathology of these diseases. Molecular docking studies revealed favorable interactions with the B. cereus SMase structure, and in silico ADME profiling suggested drug-like properties. These findings highlight novel hexahydropyrimidine derivatives as promising nSMase2 inhibitors for further investigation.\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146144385","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

Identification of Mitophagy-Related Genes With Diagnostic Value in Atherosclerosis Using Bioinformatics Analysis and Experiment Validation 应用生物信息学分析和实验验证鉴定动脉粥样硬化中有丝分裂相关基因的诊断价值。

IF 3.3 4区医学

Chemical Biology & Drug Design Pub Date : 2026-02-07 DOI: 10.1111/cbdd.70260

Zhe Chen, Zhongying Chen, Yuhao Wang, Jianzhi Shao, Qizeng Wang

{"title":"Identification of Mitophagy-Related Genes With Diagnostic Value in Atherosclerosis Using Bioinformatics Analysis and Experiment Validation","authors":"Zhe Chen, Zhongying Chen, Yuhao Wang, Jianzhi Shao, Qizeng Wang","doi":"10.1111/cbdd.70260","DOIUrl":"10.1111/cbdd.70260","url":null,"abstract":"Atherosclerosis (AS) is a chronic inflammatory condition with complex molecular underpinnings, where mitophagy—selective mitochondrial autophagy—plays a critical yet poorly defined role. By integrating bulk and single-cell RNA sequencing data from human atherosclerotic plaques, we analyzed 20 mitophagy-related genes and identified 15 that were dysregulated in AS. Machine learning approaches (Random Forest and SVM-RFE) pinpointed four hub genes—PINK1, TOMM40, TOMM7, and VDAC1—which formed the basis of a diagnostic model with solid predictive performance. Single-cell analysis of over 106,000 cells revealed endothelial cells as mitophagy-active and dominant in AS lesions. Trajectory analysis distinguished disease-associated endothelial subtypes, while CellChat uncovered intensified MIF signaling via CD74-CD44 and CD74-CXCR4 axes in mitophagy-high endothelial cells. SCENIC analysis further identified CEBPD, FOS, and JUN family transcription factors as key regulators. Experimental validation using ox-LDL-treated RAW264.7 macrophages confirmed differential expression of all four hub genes. Collectively, our findings highlight endothelial mitophagy dysregulation and immune crosstalk as central to AS pathogenesis and offer promising diagnostic markers and therapeutic targets.","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133828","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