Chemical Biology & Drug Design最新文献

{"title":"EXPRESSION OF CONCERN: The Truncated Human Telomeric Sequence Forms a Hybrid-Type Intramolecular Mixed Parallel/antiparallel G-quadruplex Structure in K+ Solution","authors":"","doi":"10.1111/cbdd.70028","DOIUrl":"10.1111/cbdd.70028","url":null,"abstract":"<p><b>EXPRESSION OF CONCERN:</b> Y. Liu, D. Cheng, M. Ge, and W. Lin, “The Truncated Human Telomeric Sequence Forms a Hybrid-Type Intramolecular Mixed Parallel/antiparallel G-quadruplex Structure in K+ Solution,” <i>Chemical Biology &amp; Drug Design</i> 88, no. 1 (2016): 122-128, https://doi.org/10.1111/cbdd.12740.</p><p>This Expression of Concern is for the above article, published online on 12 February 2016, in Wiley Online Library (http://onlinelibrary.wiley.com/), and has been issued by agreement between the journal Editor-in-Chief, Roberta Melander; and John Wiley &amp; Sons Ltd. A third party reported to the publisher that the gel-shift assay image in Figure 2 shows evidence of splicing. Further analysis by the publisher has confirmed the evidence of splicing. The authors responded to an inquiry by the publisher but stated that the original data were no longer available. The authors also stated that they had adjusted the brightness levels in the gel images used in this article, but did not alter experimental results. The Expression of Concern has been agreed to because the journal and publisher agree that Figure 2 contains spliced lanes and as a result, they are not able to confirm the veracity of the experiments described in this article. The authors disagree with the Expression of Concern.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804082","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":"Design and Development of Novel Hybrids Based on Pyrrolo[2,1-f][1,2,4]Triazine and 1-(Methylpiperidin-4-yl) Aniline–Based Analogs: Exploring the Utility as Anticancer Agents via MERTK Inhibition","authors":"Balaji Dashrath Sathe,&nbsp;Shivani Jaiswal,&nbsp;Devendra Kumar,&nbsp;Thakur Gurjeet Singh,&nbsp;Nidhi Nainwal,&nbsp;Pramod Rawat,&nbsp;Savita Yadav,&nbsp;Bhupinder Kumar,&nbsp;Ashish Ranjan Dwivedi,&nbsp;S. V. Rathod","doi":"10.1111/cbdd.70023","DOIUrl":"10.1111/cbdd.70023","url":null,"abstract":"<p>Mer-tyrosine kinase (MERTK), a member of the AXL, TYRO3, and MERTK (TAM) family, is one of the promising targets for cancer treatment. It plays a key role in cancer cell survival and proliferation and regulates immune responses in cancer. The study aimed to rationally design and develop molecules considering the pharmacophoric requirements of MERTK using a multi-synthetic approach followed by the hybridization of individual pharmacophores. A hybrid drug design approach was employed by hybridization of pyrrolo[2,1-<i>f</i>][1,2,4]triazine and 1-(methylpiperidin-4-yl)aniline pharmacophoric systems to develop novel leads (<b>1K1–1K5</b>). The molecules were synthesized via a multi-step synthetic approach. The synthesized molecules were assessed for their pharmacological potential via cell viability, drug metabolism and pharmacokinetics (DMPK), and MERTK inhibition studies corroborated by in silico studies. <b>IK5</b> was found to have an IC₅₀ value of 0.36 μM towards A549, followed by 0.42 μM and 0.80 μM against MCF-7 and MDA-MB-231 cells, respectively. Further, the molecules were also analyzed for their microsomal stability and were found to be stable with better intrinsic clearance profiles. The molecules thus pave a strategy for developing novel MERTK inhibitors and their advance in vitro and in vivo assessment in the future.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788097","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":"TRIM16 and PRC1 Are Involved in Pancreatic Cancer Progression and Targeted by Delphinidin","authors":"Donghua Wang,&nbsp;Long Lv,&nbsp;Jinghu Du,&nbsp;Kui Tian,&nbsp;Yu Chen,&nbsp;Manyu Chen","doi":"10.1111/cbdd.70026","DOIUrl":"10.1111/cbdd.70026","url":null,"abstract":"<div>\u0000 \u0000 <p>Pancreatic cancer (PC) is the leading cause of cancer-related death worldwide, and new biomarkers, therapeutic targets, and candidate drugs are needed. In this work, three PC-related microarray datasets (GSE183795, GSE28735, and GSE62452) were analyzed. The differentially expressed genes (DEGs) of PC were obtained with the limma package in R. Weighted gene co-expression network analysis (WGCNA) and machine learning approaches were used to screen the hub genes. Kaplan–Meier plotter and receiver operating characteristic (ROC) curve analysis were utilized to assess the diagnostic efficacy of the hub genes. The binding ability between natural bioactive ingredients and hub proteins was evaluated by molecular docking and molecular dynamics simulation. CCK-8, flow cytometry, transwell, and western blot assays were used to analyze the viability, apoptosis, cell cycle progression, invasion, and pathway change of PC cells. Additionally, a nude mice model was used to evaluate the aggressive properties of PC cells in vivo. In this study, a total of 988 DEGs were identified, which were mainly enriched in cell adhesion and PI3K-Akt signaling pathway, and two core genes TRIM16 and PRC1 were further identified. The overall survival of patients with high expression of TRIM16 and PRC1 was shorter. Delphinidin (Del) had good binding affinity with both TRIM16 and PRC1, and Del could inhibit the viability, invasion, and metastasis of PC cells and induce cell apoptosis and G0/G1 phase arrest. In addition, Del could promote the activation of p53 and inhibit the activation of the PI3K/AKT signaling pathway in PC cells. In summary, TRIM16 and PRC1 are identified as prognostic biomarkers and therapeutic targets for PC, and Del has good binding affinity with them and may be a potential therapeutic agent for PC.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788098","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}

{"title":"Novel Hydrazide-Hydrazones Bearing a Benzimidazole Ring: Design, Synthesis, and Evaluation of Inhibitor Properties Against CA I and CA II Isozymes","authors":"Ayşen Işık,&nbsp;Ulviye Acar Çevik,&nbsp;Ismail Celik,&nbsp;Kaan Küçükoğlu,&nbsp;Hayrunnisa Nadaroglu,&nbsp;Hayrani Eren Bostancı,&nbsp;Yusuf Özkay,&nbsp;Zafer Asım Kaplancıklı","doi":"10.1111/cbdd.70025","DOIUrl":"https://doi.org/10.1111/cbdd.70025","url":null,"abstract":"<div>\u0000 \u0000 <p>In this study, we propose identifying potential novel compounds targeting carbonic anhydrase I and II. Herein, we have designed and synthesized new benzimidazole-hydrazide-hydrazones derivatives (<b>4a-4r</b>) to investigate the effects of these synthesized compounds on CA isoenzymes. The compounds' ¹H NMR, ¹³C NMR, and HRMS spectra were used to confirm their chemical structures. The synthetic derivatives were screened for their inhibitory potential against carbonic anhydrase I and II by <i>in vitro</i> assay. These compounds have IC₅₀ values of 3.727–1.493 μM (hCA I) and 3.892–1.547 μM (hCA II). Inhibition types and <i>K</i>_i values of the compounds were determined. The <i>K</i>_i values of the compounds were 3.006 ± 0.17 μM-0.356 ± 0.0 μM (hCA I) and 2.923 ± 0.15 μM-0.346 ± 0.0 μM (hCA II). Acetazolamide (AAZ) was used as the reference in the study. The most potent derivatives, a 4-methoxy derivative (compound <b>4k</b>) and 4-(trifluoromethyl) derivative (compound <b>4g</b>), than AAZ (IC₅₀ = 2.26 μM) and their IC₅₀ values were found as 1.493 μM and 1.675 μM, respectively. Compared to AAZ, the other derivatives having more effect on hCA I were compounds <b>4b</b>, <b>4e</b>, <b>4l</b>, <b>4m</b>, <b>4n</b>, and <b>4o</b>. The compounds gave IC₅₀ values of 1.743, 1.789, 1.933, 1.966, 1.983, and 1.986 μM, respectively. Compounds <b>4a-4r</b> found no more effective inhibitory activity against hCA II isozyme than AAZ (IC₅₀ = 1.17 μM). According to the <i>in vitro</i> test results, detailed protein-ligand interactions of the compounds <b>4b</b> and <b>4k</b> exhibited considerably low binding energies, suggesting strong interaction affinities against hCA I. In addition, the cytotoxic effects of the compounds on the L929 healthy cell line were evaluated.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758098","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}

{"title":"Edaravone Ameliorate Inflammation in Vitamin D3 and High Fat Diet Induced Atherosclerosis in Rat via Alteration of Inflammatory Pathway and Gut Microbiota","authors":"Lingjuan Du,&nbsp;Jia Wan,&nbsp;Guokai Yang,&nbsp;Zhenhuan Ma,&nbsp;Zhaoxiang Li,&nbsp;Guojian Li","doi":"10.1111/cbdd.70019","DOIUrl":"10.1111/cbdd.70019","url":null,"abstract":"<div>\u0000 \u0000 <p>Cardiovascular disease refers to a group of conditions that affect the heart and blood vessels, including coronary artery disease, heart failure, and stroke, among others. Edaravone (ED) inhibits oxidative stress and free radical damage, which are thought to contribute to the progression of various diseases. Thus, the purpose of the study is to examine the cardioprotective effect of ED against vitamin D₃ and high fat-induced atherosclerosis in rats. In this study, Sprague Dawley (SD) rats were utilized. The rats were separated into several groups and fed a high-fat diet along with vitamin D₃ to induce atherosclerosis. Various doses of ED were orally administered to the animals for 30 days. The administration of Edaravone effectively reduced the elevated body weight, as well as the excessive water and food consumption. The treated groups exhibited a decrease in glucose level, leptin, and apolipoprotein-B. Administration of ED also modified the cholesterol parameters, coronary artery index, atherogenic index, and antioxidant parameters. It also reduced the elevated heart rate, systolic blood pressure (BP), mean BP, and diastolic BP. The group treated with ED exhibited a decrease in the level of inflammatory cytokines. The ED significantly (<i>p</i> &lt; 0.001) reduced the levels of MMP-2, MMP-3, and MMP-9. Furthermore, it induced significant (<i>p</i> &lt; 0.001) adjustments in the abundance of Firmicutes, Bacteroidetes, Proteobacteria, Verrucomicrobia, and F/B ratio. Edaravone exhibited the cardio protection against HFD induced atherosclerosis in rats via alteration of gut microbiota.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690116","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}

{"title":"Herbacetin Inhibits Human Fructose 1,6-Bisphosphatase Among a Panel of Chromone Derivatives and Pyrazoles, Demonstrating Positive Effects on Insulin-Resistant HepG2 Cells","authors":"Sónia Rocha,&nbsp;Beatriz Vicente,&nbsp;Carina Proença,&nbsp;Vera L. M. Silva,&nbsp;Artur M. S. Silva,&nbsp;M. Luísa Corvo,&nbsp;Eduarda Fernandes,&nbsp;Marisa Freitas","doi":"10.1111/cbdd.70017","DOIUrl":"10.1111/cbdd.70017","url":null,"abstract":"<div>\u0000 \u0000 <p>In patients with type 2 diabetes <i>mellitus</i> (DM), excessive gluconeogenesis is considered a major contributor to hyperglycemia. Therefore, targeting fructose 1,6-bisphosphatase (FBPase), a key regulatory enzyme involved in gluconeogenesis, has gained interest as a potential therapeutic target for managing DM. In this study, a library of 42 structurally-related chromone derivatives (including flavonoids, 2-styrylchromones, and 2-(4-arylbuta-1,3-dien-1-yl)chromones, named as 2-styrylchromone-related derivatives), as well as 4- and 5-styrylpyrazoles, were tested against human FBPase using a noncellular microanalysis screening system. Herbacetin, 3,4′,5,7,8-pentahydroxyflavone, inhibited FBPase activity with an IC₅₀ value of 6.4 ± 0.7 μM. The effects of herbacetin were also explored using an insulin-resistant human hepatocellular carcinoma cell line (HepG2 cells). The results showed that herbacetin significantly decrease insulin resistance by promoting the phosphorylation of protein kinase B (Akt), and exhibited a capacity to ameliorate inflammation, evidenced by the modulation of the inhibitor of κB alpha (IκBα). This study provides important considerations for the design of novel FBPase inhibitors. Furthermore, it indicates a preliminary potential of herbacetin's dual action in improving insulin resistance and decreasing inflammation, suggesting the need for further investigation of this compound for addressing the complexities of type 2 DM management.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690120","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}

{"title":"Innovative Photoprotection Strategy: Development of 2-(Benzoxazol-2-Yl)[(2-Hydroxynaphthyl)Diazenyl] Phenol Derivatives for Comprehensive Absorption of UVB, UVA, and Blue Light","authors":"Karen Sousa,&nbsp;Jaqueline Nascimento Picada,&nbsp;Gabriela Rodrigues da Silva,&nbsp;Larissa da Cunha Solka,&nbsp;Iuri Marques de Oliveira,&nbsp;João Antonio Pêgas Henriques,&nbsp;Leandra Franciscato Campo,&nbsp;Dione Silva Corrêa","doi":"10.1111/cbdd.70020","DOIUrl":"10.1111/cbdd.70020","url":null,"abstract":"<div>\u0000 \u0000 <p>Overexposure to blue light due to the excessive use of electronic devices has been implicated in premature skin aging and eye damage, among other injuries to health. This study aimed to synthesize two azo derivatives of the 2-(amino-2′-hydroxyphenyl) benzoxazole and explore their potential as UV and blue light filters, proposing a new spectral profile. The synthesis of the heterocyclic compounds involved condensation reactions and diazotation. The derivatives 2-(benzoxazol-2-yl)-5-[(2-hydroxynaphthyl)diazenyl]phenol and 2-(benzoxazol-2-yl)-4-[(2-hydroxynaphthyl)diazenyl]phenol were synthesized with a yield greater than 70%. Solubility was evaluated in seven different solvents. The maximum absorption wavelengths (<i>λ</i>_max) were determined using UV–Vis scanning spectrophotometry in the range of 200–600 nm. Photostability was assessed using a solar simulator and the Sun protection factor (SPF) was determined using in vitro methodology. Cytotoxicity was evaluated using the MTT assay in V79 cells. These compounds were able to absorb UVA, UVB, and blue light, with <i>λ</i>_max ranging from 300 to 500 nm and demonstrated photostability after 3 h of exposure to solar simulator with an SPF higher than 45. The compounds exhibited solubility in all lipophilic solvents tested. Regarding cytotoxicity, IC50 values were comparable to other filters. These findings indicate that both compounds hold promise as potential organic filters.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683877","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}

{"title":"Novel Fused Pyrimidines as Potent Cyclin-Dependent Kinases Inhibitor for Gastric Adenocarcinoma: Combined In Vitro, In Silico Anticancer Studies","authors":"Natarajan Saravanakumar,&nbsp;Arunagiri Sivanesan Aruna Poorani,&nbsp;Anantha Krishnan Dhanabalan,&nbsp;Selvam Sugapriya,&nbsp;Ganesan Kumaresan,&nbsp;Palaniswamy Suresh","doi":"10.1111/cbdd.70013","DOIUrl":"10.1111/cbdd.70013","url":null,"abstract":"<div>\u0000 \u0000 <p>Our research aims to design novel pyrimidine derivatives inspired by the common pyrimidine core found in many FDA-approved drugs. However, extensive prior research on the pyrimidine scaffold has made discovering new molecules more challenging. To overcome this obstacle, we employed a molecular hybridisation strategy, opting to hybridise tetralin and pyrimidine, recognising their potential in cancer therapeutics. The fused pyrimidine was synthesised through a base-mediated condensation of chalcone with amidine. The reaction conditions were further optimised for base, solvent, temperature and time to produce a series of 21 novel derivatives. These compounds were subsequently screened for anticancer activity against gastric adenocarcinoma cell lines using the MTT assay. Among the synthesised compounds, 2-(pyridin-3-yl)-4-(pyridin-3-yl)-5,6-dihydrobenzo[h]quinazoline <b>8b</b> and 4-(2-(pyridin-3-yl)-5,6 dihydrobenzo[h]quinazolin-4-yl) phenol <b>5g</b> exhibited potent anticancer activity compared to (R)-Roscovitine. Additionally, a molecular docking study was conducted to assess the reactivity of compound <b>5g</b>, revealing that the presence of a phenolic hydroxyl group enables hydrogen bonding with CDKs and enhances anticancer activity. Furthermore, the efficacy of compound <b>5g</b> was validated through an in vitro CDK2/cyclin A2 enzyme inhibition assay. Interestingly, the observed CDK2 inhibitory activity showed a good correlation with the corresponding value for the antiproliferative activity of the tested compounds.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634574","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}

{"title":"Semisynthetic p-Coumaric Acid Derivatives as Lead Dual Inhibitors Against DPP-IV and GSK-3β for Antidiabetic Therapy","authors":"Heberth de Paula,&nbsp;Camilla Santos Bolsoni,&nbsp;Fernanda Fernandes de Souza,&nbsp;Victor Da Rocha Fonseca,&nbsp;Wanderson Romão,&nbsp;Mirela Ines de Sairre,&nbsp;Kathia Maria Honorio,&nbsp;Valdemar Lacerda Jr.,&nbsp;Pedro Alves Bezerra Morais","doi":"10.1111/cbdd.70016","DOIUrl":"10.1111/cbdd.70016","url":null,"abstract":"<div>\u0000 \u0000 <p>Type 2 diabetes mellitus is a dramatically increasing global public health challenge. The prevalence is projected almost double, from 194 million in 2003 to 333 million in 2025 with type 2 diabetes mellitus representing approximately 90%–95% of cases. Dual inhibitors for antidiabetic targets is still novel and promising strategy for discovery of more effective therapies. Ester and triazole derivatives of <i>p</i>-coumaric acid were obtained from Williamson synthesis and Microwave-assisted click reaction, respectively. Chemical structures were finely characterized through IR, 1H, and 13C NMR and HRMS. They were tested for their dual inhibitory activity against GSK-3β kinase and DPP-IV. The complexes resulting from docking were used for all-atom molecular dynamics simulations, including the enzymes in the apo form, using the GROMACS 2022.3. Two inhibitors <b>2</b> and <b>5</b> demonstrated promising inhibition at low and submicromolar against both proteins. Molecular Dynamic simulations revealed that the binding pattern of the control inhibitors were reproduced by p-coumaric acid derivatives <b>2</b> and <b>5</b> with crucial interactions involving the same residues. The p-coumaric skeleton can be considered as a promising core for GSK-3β kinase and DPP-IV dual inhibitors.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634583","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}

{"title":"Chromone Derivatives as a Novel NOX4 Inhibitor: Design, Synthesis, and Regulation of ROS in Renal Fibroblast","authors":"Siming Wu,&nbsp;Lei Zhang,&nbsp;Chao Hao,&nbsp;Binhao Ma,&nbsp;Zhaohui Li,&nbsp;Shurong Fan,&nbsp;Qianbin Li,&nbsp;Gaoyun Hu,&nbsp;Zhuo Chen","doi":"10.1111/cbdd.70015","DOIUrl":"10.1111/cbdd.70015","url":null,"abstract":"<div>\u0000 \u0000 <p>Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) has emerged as a promising target for developing drugs to tackle renal fibrosis. In this study, a series of chromone derivatives were designed and synthesized. Additionally, we established a NOX4 overexpression model using the NRK-49F rat renal fibroblasts cell line and identified compound <b>14m</b> as highly active through the assessment of intracellular reactive oxygen species (ROS) levels in this model. The drug affinity responsive target stability (DARTS) assay illuminated the robust binding stability of <b>14m</b> with NOX4. Mechanistic studies further substantiated its efficacy in ameliorating fibrosis and inflammation. This investigation positions <b>14m</b> as a noteworthy NOX4 inhibitor, shedding light on its regulatory role in renal fibroblasts. Importantly, it diversifies the structural landscape of NOX4 inhibitors, offering novel lead compounds for future development.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634568","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}