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

Exploring Flavonoids as Regulators of MMP-2 and MMP-9 in Cancer Pathogenesis 黄酮类化合物在肿瘤发病机制中作为MMP-2和MMP-9调控因子的研究

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-06-17 DOI: 10.1111/cbdd.70145

Ha Vy Thi Vo, Geewoo Nam Patton, Song Ja Kim, Namdoo Kim, Hyuck Jin Lee

{"title":"Exploring Flavonoids as Regulators of MMP-2 and MMP-9 in Cancer Pathogenesis","authors":"Ha Vy Thi Vo, Geewoo Nam Patton, Song Ja Kim, Namdoo Kim, Hyuck Jin Lee","doi":"10.1111/cbdd.70145","DOIUrl":"https://doi.org/10.1111/cbdd.70145","url":null,"abstract":"<div>\u0000 \u0000 <p>Last few decades, extensive research efforts have been dedicated to uncovering novel cancer treatments. Among the most vital targets in this pursuit are matrix metalloproteinases (MMPs), enzymes integral to the progression and spread of cancer. Their role in tumor development and metastasis positions MMPs as key players in cancer pathogenesis, offering promising avenues for therapeutic intervention. Specifically, MMP-2 and MMP-9 have emerged as promising targets in cancer treatment based on their critical roles in cell invasion, angiogenesis, immune evasion, and metastasis. Studies indicate the potential of plant-derived natural products as anticancer agents through the regulation of MMP activity. Among various phytochemicals, flavonoids are reported to exhibit inhibitory activities against MMPs and antioxidant properties that present them as candidates for anticancer molecules. In this study, the potential of flavonoids as anticancer agents was explored by investigating the effects of flavonoids on (i) cancer cell viability and migration, (ii) enzymatic activity and cellular expression of MMP-2/9, and (iii) the MAPK signaling pathway. Docking simulation data regarding the interactions between MMP-2/9 and selected flavonoids provide an in-depth look at the potential mechanisms through which these molecules suppress the enzymatic activities of MMPs. Select flavonoids exhibited notable efficacy in suppressing cell proliferation and migration in A549 cells, which may be a consequence of their ability to attenuate MMP activity and expression through the suppression of the MAPK signaling pathway. These observations demonstrate the prospect of flavonoids as a naturally occurring molecular framework for the development of novel anticancer therapeutics.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308976","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

Anti-Osteoporosis Activity of Lycopene Through ESR1: Network Pharmacology, Molecular Docking, Imaging Technology, and Experimental Validation 番茄红素通过ESR1抗骨质疏松：网络药理学、分子对接、成像技术及实验验证

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-06-12 DOI: 10.1111/cbdd.70135

Benqian Zhao, Lulu Chen, Wei Wang, Weinan Xu, Bing Xu

{"title":"Anti-Osteoporosis Activity of Lycopene Through ESR1: Network Pharmacology, Molecular Docking, Imaging Technology, and Experimental Validation","authors":"Benqian Zhao, Lulu Chen, Wei Wang, Weinan Xu, Bing Xu","doi":"10.1111/cbdd.70135","DOIUrl":"https://doi.org/10.1111/cbdd.70135","url":null,"abstract":"<div>\u0000 \u0000 <p>Osteoporosis is a widespread metabolic bone disorder. Lycopene (LYC), a potent antioxidant in tomatoes, has been shown to exhibit anti-osteoporosis effects. Here, we elucidated its molecular determinants in treating osteoporosis. Network pharmacology and molecular docking were utilized to screen target proteins of LYC in osteoporosis treatment. KEGG pathway and GO enrichment analyses were used to observe biological functions of these target proteins. The osteoblastic differentiation of human marrow-derived mesenchymal stem cells (hBMSCs) was induced and evaluated by ALP staining and activity assay, Alizarin Red S (ARS) staining, and related protein expression analysis. An osteoporotic mouse model was induced by ovariectomy (OVX). For the anti-osteoporosis effect of LYC, network pharmacology and molecular docking showed estrogen receptor 1 (ESR1) as a potential therapeutic target, and KEGG pathway enrichment analysis suggested the involvement of the PI3K/AKT pathway. LYC promoted osteogenic differentiation of hBMSCs and increased ESR1 expression in the hBMSC osteogenic differentiation process in vitro. LYC diminished bone loss and increased ESR1 expression in OVX mice. Reduction of ESR1 attenuated LYC-induced osteogenic differentiation of hBMSCs. Moreover, LYC activated the PI3K/AKT pathway in the hBMSC osteogenic differentiation process by upregulating ESR1. Our findings suggest that LYC induces osteogenic differentiation of hBMSCs by the ESR1/PI3K/AKT pathway, thereby contributing to its anti-osteoporosis effect. Our study provides a molecular basis for the potential application of LYC as a therapeutic agent in osteoporosis.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273174","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

δ-Tocotrienol Potentiates Breast and Prostate Cancer Cells to Paclitaxel via Suppressing PD-L1-Mediated Cancer-Promoting Signaling δ-生育三烯醇通过抑制pd - l1介导的促癌信号使乳腺癌和前列腺癌细胞对紫杉醇有增强作用

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-06-12 DOI: 10.1111/cbdd.70143

Zhenou Sun, Xuan Ma, Jiaxuan Li, Lihong Fan, Chong Zhao, Shutao Yin, Hongbo Hu

{"title":"δ-Tocotrienol Potentiates Breast and Prostate Cancer Cells to Paclitaxel via Suppressing PD-L1-Mediated Cancer-Promoting Signaling","authors":"Zhenou Sun, Xuan Ma, Jiaxuan Li, Lihong Fan, Chong Zhao, Shutao Yin, Hongbo Hu","doi":"10.1111/cbdd.70143","DOIUrl":"https://doi.org/10.1111/cbdd.70143","url":null,"abstract":"<div>\u0000 \u0000 <p>Vitamin E can exert either a cancer preventive effect or improve the therapeutic efficacy of chemotherapeutic drugs against multiple types of cancer. Ample evidence suggests that the cancer preventive activity of vitamin E is form-dependent; however, it is not clear whether its chemosensitization effect is also influenced by its forms. The objectives of this study were to investigate whether the eight natural forms of vitamin E produced differential sensitization effects on cancer chemotherapeutic drugs and to address whether the chemosensitization effect of vitamin E was associated with its inhibitory effect on programmed cell death ligand 1 (PD-L1) signaling. We carried out a comparative evaluation of the chemosensitization effect of eight vitamin E forms using paclitaxel as a representative therapeutic drug and breast/prostate cancer as the representative types of cancer. Results showed that the sensitization effect of vitamin E on chemotherapeutic drugs was also form-dependent, with δ-tocotrienol (δ-T3) as the most effective one for sensitizing breast and prostate cancer cells to paclitaxel, mechanistically associated with its ability to suppress PD-L1-mediated tumor-promoting signaling. The findings provided novel insights into understanding the sensitization effect of vitamin E and its related mechanisms and support that δ-T3 is the best candidate as an enhancer of taxanes among the eight forms.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144273361","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

Targeting Cancer Cell Proliferation Using Piperazine-Linked Quinolinequinones: Mechanism and Metabolic Profile 利用哌嗪类喹啉醌靶向癌细胞增殖：机制和代谢谱

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-06-11 DOI: 10.1111/cbdd.70139

Ayse Mine Yilmaz, Ayse Tarbin Jannuzzi, Abanish Biswas, Subodh Mondal, Vinay N. Basavanakatti, Hatice Yıldırım, Mahmut Yıldız, Nilüfer Bayrak, Venkatesan Jayaprakash, Amaç Fatih TuYuN

{"title":"Targeting Cancer Cell Proliferation Using Piperazine-Linked Quinolinequinones: Mechanism and Metabolic Profile","authors":"Ayse Mine Yilmaz, Ayse Tarbin Jannuzzi, Abanish Biswas, Subodh Mondal, Vinay N. Basavanakatti, Hatice Yıldırım, Mahmut Yıldız, Nilüfer Bayrak, Venkatesan Jayaprakash, Amaç Fatih TuYuN","doi":"10.1111/cbdd.70139","DOIUrl":"https://doi.org/10.1111/cbdd.70139","url":null,"abstract":"<p>A series of aminated quinolinequinones linked to piperazine analogs (<b>QQ1-7</b>) were synthesized and screened against the full panel of National Cancer Institute (NCI) cancer cell lines for their potential as cytotoxic agents. The Developmental Therapeutics Program of the NCI analyzed the NCI-60 screening results and revealed that seven QQs were potent inhibitors of cancer cell growth across several cell lines, advancing them to the five-dose assay. Encouraged by the NCI five-dose assay results, the cytotoxicity of the selected QQs (<b>QQ1</b> and <b>QQ4</b>) was further studied in three cancer cell lines—HCT-116 (colon cancer), ACHN (renal cancer), MCF7, and T-47D (breast cancer)—as well as in a normal cell line (HUVEC) for a deeper understanding. <b>QQ1</b> was the hit compound for ACHN cells with an IC<sub>50</sub> value of 1.55 μM. <b>QQ1</b> could inhibit ACHN cell proliferation, induce oxidative stress, and cause cell cycle arrest in ACHN cells. <b>QQ1</b> did not affect the apoptotic value in ACHN cells. Oral bioavailability was poor for both <b>QQ1</b> and <b>QQ4</b> in vivo in rats due to faster intrinsic hepatic clearance in comparison with humans, as evidenced by in vitro metabolic studies with rat and human liver microsomes. Molecular docking simulation with putative target CDC25A revealed the interaction of <b>QQ1</b> and <b>QQ4</b> with active site residues responsible for substrate recognition.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264401","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

Extraction, Structural Analysis, and Bioactivity of a Novel Polysaccharide From Corydalis yanhusuo Residues 一种新型延胡索多糖的提取、结构分析及生物活性研究

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-06-10 DOI: 10.1111/cbdd.70115

Si-qi Zhang, Si-mei Liu, Zi-long Chen, Ke Guo, Xin-xin Yang, Li-hua Zhang, Ya-feng Yan, Ting-ting Zhang, Peng Zhao

{"title":"Extraction, Structural Analysis, and Bioactivity of a Novel Polysaccharide From Corydalis yanhusuo Residues","authors":"Si-qi Zhang, Si-mei Liu, Zi-long Chen, Ke Guo, Xin-xin Yang, Li-hua Zhang, Ya-feng Yan, Ting-ting Zhang, Peng Zhao","doi":"10.1111/cbdd.70115","DOIUrl":"https://doi.org/10.1111/cbdd.70115","url":null,"abstract":"<div>\u0000 \u0000 <p>This research extracted and purified polysaccharides from <i>Corydalis yanhusuo</i> residue. The structure of purified polysaccharides of <i>Corydalis yanhusuo</i> (CYP-1) was characterized by methods such as infrared spectroscopy, nuclear magnetic resonance, and monosaccharide composition analysis. In addition, the purified polysaccharides were subjected to preliminary studies in vitro for antioxidant and antitumor activities. The average molecular weight of CYP-1 was 1.427 × 10³ kDa. FT-IR analysis revealed that CYP-1 displayed characteristic absorption bands typical of polysaccharides. Furthermore, NMR spectroscopy suggested that the sugar residue units of CYP-1 consisted of →1)-α-D-Glcp-(4→, →6)-α-D-Galp-(1→, and α-D-Arap-(1→. In vitro bioactivity experiments revealed that CYP-1 exhibits antioxidant activity and effectively inhibits HepG2 cell proliferation with an IC<sub>50</sub> value of 1.381 mg/mL, suggesting its potential as a natural antioxidant and antitumor agent.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144255900","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

Glutamine Attenuates Inflammation and Oxidative Stress in Ulcerative Colitis by Suppressing Wilms' Tumor 1 Associated Protein-Mediated N6-Methyladenosine Modification of Nuclear Receptor Coactivator 3 谷氨酰胺通过抑制Wilms' Tumor 1相关蛋白介导的核受体共激活因子3的n6 -甲基腺苷修饰减轻溃疡性结肠炎的炎症和氧化应激

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-06-09 DOI: 10.1111/cbdd.70110

Liangxian Jiang, Shuai Liu, Feifei Ye, Xiaowei Yu

{"title":"Glutamine Attenuates Inflammation and Oxidative Stress in Ulcerative Colitis by Suppressing Wilms' Tumor 1 Associated Protein-Mediated N6-Methyladenosine Modification of Nuclear Receptor Coactivator 3","authors":"Liangxian Jiang, Shuai Liu, Feifei Ye, Xiaowei Yu","doi":"10.1111/cbdd.70110","DOIUrl":"https://doi.org/10.1111/cbdd.70110","url":null,"abstract":"<div>\u0000 \u0000 <p>Ulcerative colitis (UC) is a chronic inflammatory condition. Glutamine (Gln) has shown an improved effect on UC. However, its molecular determinants are incompletely understood. NCM460 cells were stimulated with lipopolysaccharide (LPS) to generate an in vitro UC cell model, and dextran sulfate sodium (DSS)-induced UC models were established in mice. Methylated RNA immunoprecipitation (MeRIP) and messenger RNA (mRNA) stability experiments were used to validate the influence of Wilms' tumor 1-associating protein (WTAP) on nuclear receptor coactivator-3 (NCOA3) mRNA. In LPS-exposed NCM460 cells, Gln promoted NCOA3 expression and reduced WTAP expression. Gln relieved LPS-triggered inflammation, oxidative stress, and apoptosis in NCM460 cells, which were abolished by NCOA3 downregulation or WTAP upregulation. Mechanistically, Gln suppressed WTAP-mediated m6A modification of NCOA3 mRNA. WTAP reduction attenuated LPS-evoked NCM460 cell phenotype alterations, which were reversed by NCOA3 downregulation. Furthermore, Gln reduced the DAI score and histopathological changes, increased colon length, and attenuated inflammation and oxidative stress in DSS-induced UC mice, which were abrogated by WTAP increase. We showed that the WTAP/NCOA3 axis underlies the protective effect of Gln on UC, providing a rationale for Gln as a promising anti-UC agent.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244490","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

Erianin Protects Human Umbilical Vein Endothelial Cells From Oxidized Low-Density Lipoprotein-Induced Apoptosis and Oxidative Stress Through Activation of Nuclear Factor E2-Related Factor 2 Signaling 鸢尾素通过激活核因子e2相关因子2信号通路，保护人脐静脉内皮细胞免受氧化性低密度脂蛋白诱导的凋亡和氧化应激

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-06-09 DOI: 10.1111/cbdd.70104

Zhaowei Wang, Linru Wang, Yuanyuan Wang, Juanzi Zhang

{"title":"Erianin Protects Human Umbilical Vein Endothelial Cells From Oxidized Low-Density Lipoprotein-Induced Apoptosis and Oxidative Stress Through Activation of Nuclear Factor E2-Related Factor 2 Signaling","authors":"Zhaowei Wang, Linru Wang, Yuanyuan Wang, Juanzi Zhang","doi":"10.1111/cbdd.70104","DOIUrl":"https://doi.org/10.1111/cbdd.70104","url":null,"abstract":"<div>\u0000 \u0000 <p>Oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell damage plays an important role in the pathogenesis of atherosclerosis (AS). This study aimed to investigate the ability of Erianin to protect human umbilical vein endothelial cells (HUVECs) against ox-LDL-induced oxidative stress and its underlying mechanisms. HUVECs were treated with Erianin (0, 5, 10, and 20 μM) for 2 h and then stimulated with ox-LDL (100 μg/mL) for 24 h. Flow cytometry and MTT assay determined cell apoptosis and viability, respectively. The protein levels of caspase-9, caspase-3, cleaved poly (ADP-ribose) polymerase-1 (PARP-1), nuclear factor E2-related factor 2 (Nrf2), histone H3, NAD(P)H: quinone oxidoreductase-1 (NQO-1), heme oxygenase-1 (HO-1), cytochrome c, and cytochrome c oxidase subunit IV (COX IV) were evaluated by Western blot. Matrix metalloproteinase (MMP) membrane potential was measured. The impact of Erianin on ox-LDL-induced injury in HUVECs was confirmed by using small interfering RNA si-Nrf-2. Erianin pretreatment notably rescued the impaired ox-LDL-treated HUVEC viability and apoptosis and inhibited ox-LDL-induced mitochondrial dysfunction in HUVECs. Furthermore, Erianin reduced ox-LDL-induced oxidative stress by enhancing Nrf2 signaling activation, and Nrf2 knockdown by siRNAs diminished the anti-oxidative role of Erianin in HUVECs. These suggest that Erianin suppresses ox-LDL-induced apoptosis and oxidative stress by regulating Nrf2 signaling in HUVECs.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244488","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

Discovery of Small Molecule PD-L1 Inhibitors via Optimization of Solvent-Interaction Region for Cancer Immunotherapy 通过优化溶剂相互作用区发现小分子PD-L1抑制剂用于癌症免疫治疗

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-06-09 DOI: 10.1111/cbdd.70141

Binbin Cheng, Ting Liu, Hao Cao, Jin Liu, Yichang Ren, Junli Huang, Dulin Kong, Ting Chen, Yong Liu, Jianjun Chen

{"title":"Discovery of Small Molecule PD-L1 Inhibitors via Optimization of Solvent-Interaction Region for Cancer Immunotherapy","authors":"Binbin Cheng, Ting Liu, Hao Cao, Jin Liu, Yichang Ren, Junli Huang, Dulin Kong, Ting Chen, Yong Liu, Jianjun Chen","doi":"10.1111/cbdd.70141","DOIUrl":"https://doi.org/10.1111/cbdd.70141","url":null,"abstract":"<div>\u0000 \u0000 <p>Despite extensive research, the topic of anti-PD-L1 small-molecule inhibitors remains elusive. Herein, we report the design, synthesis, and bioevaluation of a series of small molecule PD-L1 inhibitors via optimization of the solvent-interaction region. Among them, compound <b>GJ19</b> showed the most potent anti-PD-L1 effects with an IC<sub>50</sub> of 32.06 nM in the HTRF (homogenous time-resolved fluorescence) assay, better than <b>BMS-202</b> (IC<sub>50</sub> = 62.1 nM). In addition, the SPR (surface plasmon resonance) assay revealed that <b>GJ19</b> can effectively bind to human/murine PD-L1 protein with <i>K</i><sub>D</sub> values of 171 and 290 nM, respectively. Furthermore, <b>GJ19</b> concentration-dependently promoted HepG2 cell mortality in a co-culture model of HepG2/hPD-L1 and Jurkat T/hPD-1 cells. In the in vivo efficacy studies, <b>GJ19</b> (intraperitoneal injection, 15 mg/kg) effectively suppressed tumor growth with a TGI of 56.8% in a B16-F10 melanoma mouse model by activating antitumor immunity. In conclusion, <b>GJ19</b> represents a potential small molecule inhibitor of PD-L1, deserving further investigation for tumor immunotherapy.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244489","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

Ferulic Acid Inhibits Partial Epithelial-Mesenchymal Transition in Renal Tubular Epithelial Cells and Mitigates Renal Interstitial Fibrosis by Regulating the HIF-1α/Twist Signaling Pathway 阿魏酸通过调控HIF-1α/Twist信号通路抑制肾小管上皮细胞部分上皮-间质转化并减轻肾间质纤维化

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-06-09 DOI: 10.1111/cbdd.70133

Lin Xu, Dongsheng Yao, Tianying Lan, Yurou Chen, Dongping Chen, Minghai Shao, Yijing Zhou, Chaoyang Ye, Di Huang

{"title":"Ferulic Acid Inhibits Partial Epithelial-Mesenchymal Transition in Renal Tubular Epithelial Cells and Mitigates Renal Interstitial Fibrosis by Regulating the HIF-1α/Twist Signaling Pathway","authors":"Lin Xu, Dongsheng Yao, Tianying Lan, Yurou Chen, Dongping Chen, Minghai Shao, Yijing Zhou, Chaoyang Ye, Di Huang","doi":"10.1111/cbdd.70133","DOIUrl":"https://doi.org/10.1111/cbdd.70133","url":null,"abstract":"<div>\u0000 \u0000 <p>Ferulic acid (FA), a natural phenolic compound, shows potential therapeutic effects on renal interstitial fibrosis, although its antifibrotic mechanism remains unclear. This study investigated the molecular mechanisms of FA by focusing on epithelial-mesenchymal transition (EMT) and related signaling pathways. By using a hypoxia-induced HK2 cell model, the optimal FA concentration was determined by CCK-8 assay, and the cells were assigned to low-, medium-, and high-FA groups. Renal fibrosis-associated protein and mRNA levels were evaluated by western blotting (WB) and reverse transcription-quantitative polymerase chain reaction. In a 5/6 nephrectomy-induced chronic renal failure rat model, renal oxygen consumption, serum creatinine, and blood urea nitrogen levels were measured, while ultrastructural and morphological changes in renal tissues were examined by transmission electron microscopy (TEM), hematoxylin–eosin (HE) staining, and Masson's trichrome staining. Renal fibrosis-related indicators were further assessed by Western Blot (WB) and immunofluorescence assay. The results showed that FA treatment significantly reduced fibronectin, HIF-1α, and α-SMA expression; inhibited partial EMT in vivo and in vitro; improved renal function; and attenuated fibrosis in kidney tissues. Combining siTwist or oe-HIF-1α transfection with FA treatment revealed that FA targeted the HIF-1α/Twist signaling pathway, impeding EMT and delaying renal fibrosis. In conclusion, FA inhibited partial EMT of tubular epithelial cells and suppressed the HIF-1α/Twist pathway, thereby mitigating renal interstitial fibrosis and providing a foundation for FA-based treatment of chronic kidney disease.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244396","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 a Selective Cell-Active Inhibitor of Protein Arginine Methyltransferase 5 (PRMT5) for the Treatment of Prostate Cancer by Structure-Based Virtual Screening 蛋白精氨酸甲基转移酶5 （PRMT5）选择性细胞活性抑制剂在前列腺癌治疗中的应用

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-06-04 DOI: 10.1111/cbdd.70136

TongXiang Diao, Chen Feng, Shuai Liu, Jia-Li Song, Kong-kai Zhu, Cheng-Shi Jiang, Qiang Fu

{"title":"Identification of a Selective Cell-Active Inhibitor of Protein Arginine Methyltransferase 5 (PRMT5) for the Treatment of Prostate Cancer by Structure-Based Virtual Screening","authors":"TongXiang Diao, Chen Feng, Shuai Liu, Jia-Li Song, Kong-kai Zhu, Cheng-Shi Jiang, Qiang Fu","doi":"10.1111/cbdd.70136","DOIUrl":"https://doi.org/10.1111/cbdd.70136","url":null,"abstract":"<p>Protein arginine methyltransferase 5 (PRMT5) is an epigenetic-related enzyme that has been shown to be a promising target for the treatment of human cancers. In prostate cancer, gene knockout has been shown to inhibit cancer cells by regulating the androgen receptor (AR), but this method has no effect on advanced prostate cancer without AR expression, and existing anticancer drugs are effective only in the current stage and promote the progression of cancer to advanced prostate cancer. We hope to design and synthesize a new compound that can inhibit prostate cancer at different stages. A series of candidate PRMT5 inhibitor molecules were designed on the basis of virtual molecular docking screening, and the binding mode was predicted via molecular docking simulation. Prostate cancer cell proliferation was detected by CCK-8, EdU, and flow assays, which verified the changes in the cancer cell cycle. Migration and invasion assays verified the effects of the compounds on the metastatic function of prostate cancer cells. Finally, Western blotting was used to detect the mechanism of action of the compounds in the treatment of prostate cancer. In prostate cancer, gene knockout has been shown to inhibit cancer cells by regulating the AR, but it has no effect on advanced prostate cancer without AR expression, and existing anticancer drugs are effective only in the current stage and promote the progression of cancer to advanced prostate cancer. <b>SJL2-1</b> may be a promising compound for novel therapies for early androgen-sensitive prostate cancer and advanced castration-resistant prostate cancer (CRPC).</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144213776","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}

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