Chemical Biology & Drug Design最新文献

{"title":"Machine Learning-Guided Discovery of Novel Inhibitors of Escherichia coli MurB","authors":"Shuhua Song,&nbsp;Qingxin Liu,&nbsp;Aoqi Luo,&nbsp;Xiao Shi,&nbsp;Xinxin Si","doi":"10.1111/cbdd.70422","DOIUrl":"https://doi.org/10.1111/cbdd.70422","url":null,"abstract":"<p>MurB, a key enzyme involved in bacterial cell wall biosynthesis, represents a promising target for antibacterial drug discovery. In this study, a machine learning assay was employed to identify potential inhibitors targeting <i>E. coli</i> MurB. Five machine learning models were constructed using AutoMolDesigner, of which the RDKit_2D<i>-</i>based Model_2 was selected as the optimal activity<i>-</i>prediction model for virtual screening of an in<i>-</i>house compound library, yielding 238 compounds. These compounds were subsequently subjected to FRED molecular docking, and 16 candidate compounds were selected based on their hydrogen<i>-</i>bond interactions with the key active<i>-</i>site residue ASN A:233. Preliminary enzyme inhibition assays conducted at 50 μM identified 4 compounds (Q9, Q11, Q12, and Q13) with inhibition rates exceeding 50%. Further IC₅₀ determination revealed values of 34.44, 31.45, 25.08, and 25.94 μM, respectively. Molecular dynamics simulations combined with principal component analysis were performed to investigate the dynamic behaviors and binding stability of the MurB<i>-</i>ligand complexes. In addition, a CCK<i>-</i>8 assay was conducted in HepG2 cells to evaluate the cytotoxicity of the active compounds preliminarily. Collectively, 4 low<i>-</i>cytotoxic micromolar MurB inhibitors were identified in this study, offering promising scaffolds for further mechanistic investigation and structural optimization.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"108 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70422","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149311483","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}

{"title":"Analysis and Identification of Candidate Genes Associated with M1 Macrophage Infiltration and Glycolysis in Breast Cancer","authors":"Liang Zhang,&nbsp;Lingyuan Wu,&nbsp;Can Xu,&nbsp;Chao Fang,&nbsp;Xingsong Tian,&nbsp;Kunbing Zhu","doi":"10.1111/cbdd.70437","DOIUrl":"10.1111/cbdd.70437","url":null,"abstract":"<p>Macrophage polarization and glycolytic reprogramming contribute to the breast cancer microenvironment. However, the genes associated with these features and their clinical relevance remain poorly defined. Breast cancer transcriptomic datasets were analyzed using immune deconvolution, single-sample gene set enrichment analysis, and weighted gene coexpression network analysis. We identified 101 genes shared by the M1 macrophage-associated, glycolysis-related, and differentially expressed gene sets. Eight genes showed suggestive genetically predicted associations with BC risk. Machine learning selected seven consensus genes. In TCGA-BRCA, six genes differed significantly between tumor and normal tissue, but only five changed in the same direction as in GSE65194. In the 56 paired clinical tissues, ADAM15, PPP1R14B, and XPO5 were upregulated in tumors, whereas FAM172A and PPM1M were downregulated. ADAM15, PPP1R14B, and XPO5 were preferentially expressed in M1-like TAMs, whereas FAM172A and PPM1M showed higher expression in M2-like TAMs. In BMDMs, overexpression of ADAM15, XPO5, or PPP1R14B, as well as knockdown of PPM1M or FAM172A, increased the proportion of CD80-positive cells and ATP, glucose uptake, and lactate production. Five genes showed significant associations with overall survival. Functional enrichment analyses implicated immune regulation, extracellular matrix organization, and metabolic pathways.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"108 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70437","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149345105","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}

{"title":"Revealing the Action Mechanism of WISP2 in Miscarriage Based Multi-Omic Analysis and Experimental Validation","authors":"Zhe Leng,&nbsp;Boyu Yan,&nbsp;Fang Wang,&nbsp;Xinyi Bian,&nbsp;Yu Huang,&nbsp;Hongjuan Lv,&nbsp;Zhou Jiang,&nbsp;Xianli Sun","doi":"10.1111/cbdd.70423","DOIUrl":"10.1111/cbdd.70423","url":null,"abstract":"<p>Recurrent miscarriage (RM) is a major unresolved issue in reproductive medicine. Although WISP2 is known to participate in multiple cellular processes, its function in trophoblast biology and pregnancy maintenance remains unknown. We performed single-cell RNA sequencing on chorionic villus tissues from RM patients and normal controls to identify cell-type-specific transcriptional alterations, which led to the identification of WISP2 as a candidate gene in the SCT/EVT subpopulation. Fetal membrane samples (chorion) were obtained from Qingdao Women and Children's Hospital's Surgical Outpatient Department: 20 RM patients and 20 healthy controls. Using qRT-PCR, Western blot, and immunohistochemistry to detect gene and protein expression. HTR-8 cells were used to construct WISP2 overexpressing cells, and MTT, wound healing and Transwell experiments were performed for functional experiments. Eleven cell classes in the sample were demonstrated by single-cell analysis. Among these cells were DSCs and SCT/extravillous trophoblasts (EVT). The level of WISP2 is low in SCT/EVT cells from RM patients. In chorionic villus tissues, both WISP2 and E-cadherin were significantly upregulated in the RM group relative to the control group (all <i>p</i> &lt; 0.05). Immunohistochemistry confirmed elevated WISP2 and E-cadherin protein levels in RM chorionic villi (both <i>p</i> &lt; 0.05), with predominant cytoplasmic and membranous localization, respectively. In HTR-8 cells, WISP2 overexpression suppressed proliferation (35%, <i>p</i> &lt; 0.01), migration (45%, <i>p</i> &lt; 0.01), and invasion (50%, <i>p</i> &lt; 0.001), upregulated E-cadherin (<i>p</i> &lt; 0.05), downregulated Vimentin (<i>p</i> &lt; 0.05), and increased p-ERK (<i>p</i> &lt; 0.05) without altering total ERK1/2 (<i>p</i> &gt; 0.05), suggesting that WISP2 promotes an epithelial-like phenotype accompanied by ERK pathway activation. In summary, WISP2 is dysregulated in RM and suppresses trophoblast invasion and EMT in vitro, suggesting a potential role in RM pathogenesis, though in vivo validation is required.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"108 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70423","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149345106","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}

{"title":"LncRNA MALAT1 Targets METTL3 to Orchestrate INPP5B/LRIG2 Signaling and Promote Non-Small Cell Lung Cancer Progression","authors":"Shuhong Tian,&nbsp;Fayu Ling,&nbsp;Dunzhi Fu,&nbsp;Qiongyu Wang,&nbsp;Fan Li,&nbsp;Biao Li","doi":"10.1111/cbdd.70421","DOIUrl":"https://doi.org/10.1111/cbdd.70421","url":null,"abstract":"<p>m⁶A modification regulates the functions of long non-coding RNAs (lncRNAs) through diverse mechanisms. However, whether the lncRNA MALAT1 regulates the progression of non-small cell lung cancer (NSCLC) through targeted regulation of METTL3 remains unclear, and the underlying molecular mechanisms have yet to be elucidated. This study aimed to investigate the role of MALAT1 in NSCLC progression by targeting and regulating METTL3. NCI-H226 NSCLC cells were used as experimental models. RIP and FISH assays were performed to validate the physical interaction between MALAT1 and METTL3. Cells were co-transfected with si-MALAT1 and METTL3 overexpression constructs for rescue experiments. FISH was used to determine the subcellular localization of MALAT1. Apoptotic activity was quantified by flow cytometry, while cell proliferation was assessed using the EdU incorporation assay. The Transwell assay was performed to evaluate cell migration, and the EpiQuik m⁶A RNA Methylation Quantification Kit was used to detect cellular m⁶A methylation levels. Xenograft mouse models were established to evaluate in vivo tumor growth, and clinical NSCLC specimens were analyzed to investigate the clinical correlation among METTL3, INPP5B, and LRIG2. The experimental results showed that MALAT1 was predominantly localized in the nucleus and interacted with METTL3. Following si-MALAT1 treatment, cell proliferation and migration were decreased, although no significant change was observed in colony formation ability. Furthermore, apoptosis was increased, accompanied by cell cycle arrest at the G0/G1 phase. After MALAT1 interference, transfection with a METTL3 overexpression vector reversed these malignant phenotypes, reduced apoptosis, induced S-phase accumulation, and significantly downregulated the tumor suppressor gene INPP5B while upregulating the oncoprotein LRIG2. Consistently, in vivo xenograft assays demonstrated that MALAT1 knockdown suppressed tumor growth, which was rescued by METTL3 overexpression. Clinical sample analysis further supported the correlation among METTL3, INPP5B, and LRIG2 in NSCLC tissues. These findings substantiate the regulatory role of MALAT1-mediated METTL3 modulation in NSCLC progression through the INPP5B/LRIG2 signaling axis.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"108 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70421","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149259463","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}

{"title":"Exploration of Pyrazole-Sulfonamide Hybrids: Synthesis, Molecular Modeling, Potential Antimicrobial, DHFR Inhibitor, and Pharmacokinetic Profile","authors":"Adhwa A. Alharbi,&nbsp;Manal S. Ebaid,&nbsp;Asmaa L. Alanzy,&nbsp;Adel I. Alalawy,&nbsp;Basma Abbas,&nbsp;Khadra B. Alomari,&nbsp;Roba M. S. Attar,&nbsp;Nashwa M. El-Metwaly","doi":"10.1111/cbdd.70417","DOIUrl":"https://doi.org/10.1111/cbdd.70417","url":null,"abstract":"<p>New pyrazolyl sulfonamide conjugates <b>5</b>, <b>6</b>, and <b>7</b> were synthesized by reacting N-(4-(hydrazinecarbonyl) aryl) benzenesulfonamide with acetyl acetone, ethyl acetoacetate, and/or 2-(ethoxymethylene)malononitrile. The DFT computations of the constructed derivatives exhibited comparable bent shapes. The conjugates <b>5a-b</b> and <b>6a-b</b> displayed parallel HOMO-LUMO structures, whereas the nitro-derivatives <b>5c</b> and <b>6c</b> exhibited alternative configurations of their FMOs. Furthermore, the antimicrobial activity was assessed against different bacterial and fungal pathogens. Pyrazole derivatives <b>5c</b>, <b>6b</b>, <b>7a</b>, and <b>7c</b> exhibited high activity against <i>S. aureus</i> (MIC = 3.125–6.25 μg/mL) and <i>E. coli</i> (MIC = 3.125 μg/mL), exceeding the activity of standard antibiotics, with 6b demonstrating the broadest spectrum of activity against both bacteria and fungi. The in vitro DHFR inhibitory effects of the investigated sulfonamides were examined and compared with those of methotrexate. Among the screened derivatives, hybrids <b>7a-c</b> displayed more potent inhibitory activities, thereby determining the effect of substitution patterns on activity. Additionally, the molecular docking of the manufactured analogs against the dihydrofolate reductase enzyme (PDB: 3TZF) was investigated, where hybrid <b>6a</b> exhibited the highest activity with a binding score (<i>S</i> = −6.5129 kcal/mol), which was greater than that of methotrexate (<i>S</i> = −6.4743 kcal/mol). Moreover, pharmacokinetic characteristics were simulated using SwissADME to evaluate drug-likeness and potential oral bioavailability. All hybrids exhibited beneficial physicochemical properties within acceptable drug-likeness limits, confirming the pyrazole-sulfonamide scaffold as an optimization target for future orally active drug candidates with good pharmacokinetic potential.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"108 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70417","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149258525","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}

{"title":"Single-Cell Dissection of Inflammatory Suppression and Stemness Plasticity Reveals STMN1-Associated Malignant Epithelial Cells in Severe Lung Cancer","authors":"Yanmei Chen,&nbsp;Sisi Chen,&nbsp;Biao Cheng,&nbsp;Yuzhu Tang,&nbsp;Yiyan Huang,&nbsp;Miao Chen","doi":"10.1111/cbdd.70420","DOIUrl":"10.1111/cbdd.70420","url":null,"abstract":"<p>The disease course in patients with advanced lung cancer with malignant serous effusions (ALC-MSE) is complex, and treatment outcomes are difficult to predict; systematic studies on the tumor stem cell-like characteristics and regulatory mechanisms of this condition are still lacking. Based on single-cell transcriptomic data and the TCGA-LUAD cohort, this study systematically analyzed the functional characteristics and key regulatory networks of malignant epithelial cells in severe lung cancer. Key findings include: epithelial cells in severe lung cancer exhibit significantly attenuated inflammation- and immunity-related signaling pathways (including NF-κB, TNF, and JAK–STAT signaling pathways), enhanced stem cell-like properties, and metabolic reprogramming; we identified a highly stem-like malignant epithelial cell subpopulation, represented by Cluster 3, which is enriched in stem-like pathways such as Notch, Hippo, TGF-β, and FoxO, and is accompanied by enhanced mitochondrial metabolism and stress adaptability; STMN1 is a key molecule regulating this stem-like state, showing a significant positive correlation with stemness scores and mRNAi; cells with high STMN1 expression gain a survival advantage and may maintain their stemness by attenuating CAF/ECM signaling with other cells (COL1A1-CD44), inhibiting complement activation and antigen presentation signaling (such as C3, ANXA1, and MHC-II-related molecules), and enhancing stemness niche signaling (MIF-CD74/CD44). Furthermore, NELFE, MYBL2, FOXN3, POLR2A, and RAD21 were identified as potential upstream regulators of STMN1. In vitro experiments confirmed that, following induction of stem cell-like properties, STMN1 was significantly overexpressed in lung adenocarcinoma cells, accompanied by upregulation of related stem cell markers (SOX2, NANOG, OCT4, and CD44). In summary, this study reveals a significantly enhanced stemness state in malignant epithelial cells in advanced lung cancer, accompanied by suppressed inflammatory signaling and enhanced metabolic adaptation, and identifies STMN1 as a key molecule driving stemness maintenance and disease progression.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"108 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13685055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149240724","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}

{"title":"MSC C1: A Potential Hub Linking Stromal Plasticity, Immune Regulation, and Patient Survival in Lung Adenocarcinoma","authors":"Houlei Wang,&nbsp;Tianle Ma,&nbsp;Chao Jia,&nbsp;Chunhui Ma","doi":"10.1111/cbdd.70414","DOIUrl":"10.1111/cbdd.70414","url":null,"abstract":"<p>Bone metastasis of lung adenocarcinoma (LUAD) directly leads to poor prognosis. This study aimed to dissect the stromal landscape of LUAD with bone metastases. Unsupervised clustering of scRNA-seq data from LUAD patients with bone metastasis identifies stromal subsets. Pseudotime analysis combined with CytoTRACE stemness scoring reconstructs mesenchymal stromal cell (MSC) differentiation trajectories, while CellChat characterizes cell–cell communication networks among MSC subpopulations. Differentially expressed genes (DEGs) specific to functionally distinct MSC subsets are subjected to LASSO-Cox regression for construction of a prognostic RiskScore model, which is validated in independent bulk RNA-seq cohorts regarding overall survival, immune cell infiltration, and drug sensitivity. A distinct high-stemness MSC C1 subpopulation is localized at the bifurcation point of two divergent differentiation trajectories toward a matrix-remodeling fate and a secretory, immunomodulatory phenotype. The RiskScore model stratifies patients into low- and high-risk groups with divergent overall-survival outcomes. Reduced infiltration of cytotoxic lymphocytes is observed in high-risk patients, and higher drug sensitivity within the high-risk subgroup. In vitro assays verify that LDHA knockdown impairs proliferation and migration in A549 cells. This study provides a rationale for targeting stroma-derived genes in risk-adapted therapy.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"108 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13680633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225593","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}

{"title":"Mechanism of Qianlie Zhitong Formula Against Chronic Prostatitis Based on Proteomics and Metabolomics","authors":"Lidan Dong,&nbsp;Linhan Chang,&nbsp;Caijia Song,&nbsp;Jialin Yan,&nbsp;Tiantong Shen,&nbsp;Zhen Ding,&nbsp;Yunyu Liu,&nbsp;Chenglong Zheng,&nbsp;Yanfei Zheng,&nbsp;Qi Wang","doi":"10.1111/cbdd.70401","DOIUrl":"10.1111/cbdd.70401","url":null,"abstract":"<p>Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent pelvic pain disorder in men, yet effective pharmacotherapies remain limited. Emerging evidence suggests that oxidative stress and dysregulated iron metabolism contribute to the pathogenesis of CP/CPPS, with ferroptosis increasingly implicated in CP/CPPS-related pathology. Qianlie Zhitong Formula (QLZTF) has shown therapeutic potential in treating CP/CPPS; however, its underlying mechanisms remain incompletely understood. This study integrated proteomics, metabolomics, and in vivo experiments to investigate the therapeutic mechanisms of QLZTF. A carrageenan-induced rat model was established, and rats were randomly assigned to five groups: control, model, Qianliekang, low-dose QLZTF, and high-dose QLZTF. QLZTF significantly reduced inflammatory cytokines (TNF-α, IL-6, and IL-1β), alleviated pain responses, and ameliorated prostate tissue injury. Proteomic analysis identified BCAT2, ALDH1B1, and ALDH2 as significantly upregulated proteins closely associated with ferroptosis. KEGG enrichment analysis of both proteomic and metabolomic data revealed that pantothenate and CoA biosynthesis and branched-chain amino acid (BCAA) degradation pathways were significantly enriched. Integrated analysis indicated that QLZTF synergistically regulates these pathways, activates the BCAT2/ALDH axis, and inhibits ferroptosis, thereby alleviating inflammation, pain, and fibrosis in CP/CPPS. This study provides the first multiomics evidence for the anti-ferroptotic mechanism of QLZTF.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"108 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13680634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225579","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}

{"title":"DNAzymes and Oligodeoxyribonucleotides Immobilized on Aminopropylsilanol and Polylysine-Anatase Nanoparticles as Active Agents Against Influenza A/H5N1 Virus","authors":"Marina Repkova,&nbsp;Asya Levina,&nbsp;Ekaterina Filippova,&nbsp;Elena Makarevich,&nbsp;Maria Protsenko,&nbsp;Larisa Shishkina,&nbsp;Artemiy Sergeev,&nbsp;Valentina Zarytova","doi":"10.1111/cbdd.70419","DOIUrl":"10.1111/cbdd.70419","url":null,"abstract":"<p>The nanocomposites based on aminopropylsilanol (Si~NH₂) and polylysine-anatase (Ans/PL) nanoparticles bearing DNAzymes (Dz) and oligodeoxyribonucleotides (ON) can effectively inhibit the replication of the influenza A/H5N1 virus in cell culture. Nanocomposites based on both types of nanoparticles exhibit high activity. The Dz-containing nanocomposites exhibited higher antiviral activity than those containing ON, reducing influenza A/H5N1 virus production by 3.5 log versus 2.4–3.0 log, respectively. Notably, the effect of Dz incorporated into the nanoparticles was an order of magnitude higher than that of unbound Dz transfected with lipofectamine. Nanocomposites carrying control DNA fragments that are not specific to the influenza A virus genome have practically no antiviral activity, indicating the specificity of the proposed nanocomposites. It was demonstrated that the antiviral efficacy of the nanocomposites is primarily determined by the activity of DNA delivered into cells, which can be varied by altering either the nanocomposite concentration or its capacity for DNA fragments. All of the proposed nanocomposites can be considered as potential antiviral drugs.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"108 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70419","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198571","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}

{"title":"Synthesis of Curcumin Analogs Targeting Androgen Receptor for the Selective Inhibition of Castration-Resistant Prostate Cancer Cells","authors":"Manman Huang,&nbsp;Ziyi Chen,&nbsp;Ruiqi Zhang,&nbsp;Shengping Liu,&nbsp;Defeng Xu,&nbsp;Bing Li,&nbsp;Hang Hu","doi":"10.1111/cbdd.70418","DOIUrl":"10.1111/cbdd.70418","url":null,"abstract":"<p>In the present study, a series of curcumin analogs (A1–P3) were designed and synthesized for the inhibition of prostate cancer cells by targeting androgen receptor (AR). All synthesized compounds were structurally characterized by ¹H NMR, ¹³C NMR, and high-resolution mass spectrometry (HRMS). In vitro cytotoxicity assays demonstrated that multiple compounds exhibited comparable or improved cytotoxicity against AR-positive 22Rv1 cells as compared to dimethylcurcumin (DMC, ASC-J9). Among these compounds, compounds A2, A3, B1–B3, D1, F1, F3, G1, G3, H1, and P3 possessed higher selectivity toward prostate cancer cells as compared to DMC. Compounds O1–O3, A1–A3, B1–B3, F1, F3, G1, I1, and P3 exhibited lower cytotoxicity against AR-negative PC-3 cells than those against 22Rv1 cells. Based on the cytotoxicity results, the structure–activity relationships were analyzed. In the AR protein suppression assay, compounds O1–O3, A1–A3, and I1 exhibited similar inhibitory effects on both full-length AR (AR-FL) and AR splice variant 7 (AR-V7) as compared to DMC, while compound P3 exhibited significantly enhanced AR-FL suppression effect as compared to DMC. In comparison, compounds B2, B3, F1, and F3 exhibited reduced AR-FL and AR-V7 suppression effects as compared to DMC; B1 and G1 exhibited no significant suppression effect on AR-FL and AR-V7, suggesting that these compounds might inhibit prostate cancer cells by multiple mechanisms. Molecular docking simulations further confirmed that compounds O1–O3, A1–A3, I1, and P3 displayed high targeting ability to AR. The probable binding modes of these compounds to AR were also revealed. By modifying the molecular structure of curcumin, this study identified several compounds (A2, A3, P3) with high inhibitory activity and selectivity against castration-resistant prostate cancer cells by targeting AR-FL and AR-V7. These three compounds are promising new candidates for castration-resistant prostate cancer drug discovery.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"108 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70418","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198574","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}