Chemical Biology & Drug Design最新文献_第4页

Structure-Based Bioisosterism Design, Synthesis, Antitumor and Toxicity Assessment of Novel Aplysinopsin Analogs 新型葡糖苷类似物基于结构的生物等构设计、合成、抗肿瘤及毒性评价

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-07-11 DOI: 10.1111/cbdd.70151

Bárbara Gonçalves Rivello, Julia Biz Willig, Jéssica Gotardi, Michele Resende Machado, Gloria Narjara Santos da Silva, Christian Dias Gomides, Gisele Augusto Rodrigues de Oliveira, Luciano Morais Lião, Diogo André Pilger, Ricardo Menegatti

{"title":"Structure-Based Bioisosterism Design, Synthesis, Antitumor and Toxicity Assessment of Novel Aplysinopsin Analogs","authors":"Bárbara Gonçalves Rivello, Julia Biz Willig, Jéssica Gotardi, Michele Resende Machado, Gloria Narjara Santos da Silva, Christian Dias Gomides, Gisele Augusto Rodrigues de Oliveira, Luciano Morais Lião, Diogo André Pilger, Ricardo Menegatti","doi":"10.1111/cbdd.70151","DOIUrl":"https://doi.org/10.1111/cbdd.70151","url":null,"abstract":"<div>\u0000 \u0000 <p>Eight new LQFM's Aplysinopsin analogs (<b>12a-h</b>) were synthesized and were evaluated for their anticancer profile on MCF-7 (breast cancer), SiHA and HeLa (cervical cancer). The compounds were obtained through the rational drug design strategy, bioisosterism, by changing the indole scaffold of Aplysinopsin by phenylpyrazole, a subunit extensively explored for designing potent and selective anticancer agents. The synthesis was performed in three simple steps, followed by structural elucidation through nuclear magnetic resonance, infrared spectroscopy, and mass spectrometry, and global yield ranged from 10% to 93%. Regarding the biological assay, the best result was achieved with <b>12g</b>, which showed antiproliferative activity against all cell lines evaluated, with IC<sub>50</sub> 59.22, 58.33, and 55.32 μM for MCF-7, SiHA and HeLa, respectively. The safety profile, in the Zebrafish-based model, showed the mortality rate for <b>12g</b> in concentration-time-dependent, from 87 μM, over 120 h. All Aplysinopsin analogs demonstrated drug-likeness in agreement to Lipinski and Veber rules. Although the moderate antiproliferative activity displayed by <b>12g</b>, our results include new Aplysinopsin analogs that may be promising lead compounds for further studies, since chemical structures related to this marine compound have provided satisfactory results as anticancer agents against a variety of human tumor cell lines.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598762","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

Computationally Guided Structural Modification of Centaureidin: A Novel Approach for Enhancing Antioxidant and Antitumor Activities for Drug Development 半毛菊苷的计算导向结构修饰：增强抗氧化和抗肿瘤活性的新方法

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-07-03 DOI: 10.1111/cbdd.70149

Reem S. Alruhaimi, Emadeldin M. Kamel, Sulaiman M. Alnasser, Ibrahim Elbagory, Ayman M. Mahmoud, Al Mokhtar Lamsabhi

{"title":"Computationally Guided Structural Modification of Centaureidin: A Novel Approach for Enhancing Antioxidant and Antitumor Activities for Drug Development","authors":"Reem S. Alruhaimi, Emadeldin M. Kamel, Sulaiman M. Alnasser, Ibrahim Elbagory, Ayman M. Mahmoud, Al Mokhtar Lamsabhi","doi":"10.1111/cbdd.70149","DOIUrl":"https://doi.org/10.1111/cbdd.70149","url":null,"abstract":"<p>The development of novel therapeutic drugs with enhanced efficacy has gained significant attention in recent years. In this study, we aimed to enhance the radical scavenging and antitumor activities of centaureidin through computationally guided structural modifications. Centaureidin was initially isolated through extensive phytochemical fractionation from <i>Centaurea scoparia</i>. We employed Density Functional Theory (DFT) and multitarget molecular modeling to explore how modifying the carbon-8 (C-8) position influences bond dissociation enthalpies, radical scavenging mechanisms, and the structure-antitumor activity relationships. Guided by computational analysis, we then modified the core skeleton of centaureidin using a facile multicomponent Mannich-type synthesis, resulting in two newly substituted centaureidin analogues. The radical scavenging properties of centaureidin and its analogues CA1 and CA4 were investigated using DPPH and ABTS assays. CA1 and CA4 revealed more potent radical scavenging activities. In addition, both analogues were more effective in inhibiting the proliferation of the MCF-7 cancer cell line. All tested compounds exhibited binding affinity towards caspase-3 and the receptors EGFR, HER2 and VEGFR. In conclusion, structural modification of centaureidin resulted in enhanced antioxidant and cytotoxic activities. This comprehensive approach offers a streamlined and cost-effective pathway for drug design and development, providing valuable insights for researchers in the field of therapeutic drug production.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144550937","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

In Vitro and In Silico Evaluation of Isatin-Derived Spirooxindoles as Antituberculosis Drug Candidates isatin衍生的Spirooxindoles作为抗结核候选药物的体外和计算机评价

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-07-01 DOI: 10.1111/cbdd.70152

Fernanda Rodrigues de Lima, Jéssika de Oliveira Viana, Aleff Cruz de Castro, Rodrigo Cristiano, Marcia Alberton Perelló, Alexia de Matos Czeczot, Cristiano Valim Bizarro, Pablo Machado, Luiz Augusto Basso, Claudio Gabriel Lima-Junior, Valnês da Silva Rodrigues-Junior, Karen Cacilda Weber

{"title":"In Vitro and In Silico Evaluation of Isatin-Derived Spirooxindoles as Antituberculosis Drug Candidates","authors":"Fernanda Rodrigues de Lima, Jéssika de Oliveira Viana, Aleff Cruz de Castro, Rodrigo Cristiano, Marcia Alberton Perelló, Alexia de Matos Czeczot, Cristiano Valim Bizarro, Pablo Machado, Luiz Augusto Basso, Claudio Gabriel Lima-Junior, Valnês da Silva Rodrigues-Junior, Karen Cacilda Weber","doi":"10.1111/cbdd.70152","DOIUrl":"https://doi.org/10.1111/cbdd.70152","url":null,"abstract":"<p>Tuberculosis (TB) remains a major global health threat, exacerbated by multidrug-resistant <i>Mycobacterium tuberculosis</i> (MTB) strains. The development of new anti-TB agents is crucial. In this study, 17 isatin derivatives synthesized by our research group were evaluated for their in vitro activity against MTB strains and the two most potent compounds were assessed for cytotoxicity. Additionally, molecular docking was performed against 22 MTB protein targets to explore possible mechanisms of action, and ADMET predictions were used to determine pharmacokinetic and pharmacodynamic suitability. Also, we investigated the activity of A15, A16, and A17 against two genetically characterized multidrug-resistant clinical isolates (PT-12 and PT-20). As a result, the compounds A16 and A17 exhibited the highest anti-TB activity (MIC = 10 μM for both). Inverse molecular docking indicated the enzyme enoyl-[acyl-carrier-protein] reductase as a potential biological target. Cytotoxicity assays confirmed that A16 and A17 were non-toxic, and ADMET predictions indicated suitable drug-like properties for anti-TB therapy. Notably, A16 and A17 showed inhibitory effects against drug-resistant MTB isolates, with minimum inhibitory concentrations (MICs) ranging from 10 to 20 μM, suggesting their potential to overcome resistance mechanisms linked to mutations in katG and rpoB. These findings highlight A16 and A17 as promising candidates for anti-TB agents, particularly against multidrug-resistant strains.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70152","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524797","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

Fast Determination of Protein Binding Constants and Sites to Active Flavonoids and Phenolic Acids by Affinity Capillary Electrophoresis and Fluorescence Spectroscopy 亲和毛细管电泳和荧光光谱法快速测定蛋白质与活性黄酮类和酚酸的结合常数和位点

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-07-01 DOI: 10.1111/cbdd.70148

Pingyi Zheng, Xinru Wang, Yuchen Cui, Ruijun Tang, Hongjian Yu, Lin Wang, Youxin Li

{"title":"Fast Determination of Protein Binding Constants and Sites to Active Flavonoids and Phenolic Acids by Affinity Capillary Electrophoresis and Fluorescence Spectroscopy","authors":"Pingyi Zheng, Xinru Wang, Yuchen Cui, Ruijun Tang, Hongjian Yu, Lin Wang, Youxin Li","doi":"10.1111/cbdd.70148","DOIUrl":"https://doi.org/10.1111/cbdd.70148","url":null,"abstract":"<div>\u0000 \u0000 <p>The interaction of small molecule drugs with human serum albumin (HSA) after entering the human blood circulation system profoundly affects their distribution and absorption in the body, and further influences the activity. Thus, the in-depth investigation of drug interactions with HSA is of great significance for the optimization of drug candidates, the research and development of new drugs, and the risk assessment and control of drug combinations. Phenolic acids and flavonoids are valuable in antioxidant, antitumor, immunomodulatory studies, and many other fields, which is of great value in clinical medication. Here, the binding behaviors of 12 phenolic acids/flavonoids to HSA under physiological conditions were simultaneously investigated by affinity capillary electrophoresis (ACE) method and fluorescence spectroscopy for the first time. Results showed the binding behaviors of 12 substances were related directly to their structures. Even a little change, such as the amount of phenolic hydroxyl groups and an extra C=C bond, the binding would significantly change. Among them, rosmarinic acid (<i>K</i><sub><i>a</i></sub> = 3.880 × 10<sup>5</sup> M<sup>−1</sup>, <i>n</i> = 1.074, Sudlow site I) showed the best binding ability. Caffeic acid trended to bind with Sudlow site II, which meant it could cooperate with the other active phenolic acids/flavonoids (like dihydromyricetin and rosmarinic acid) in clinical medication to increase the curative effect. Fluorescence method verified the accuracy of the results determined by ACE. However, it showed some limitations such as fluorescence interference, indicating it was not suitable for some determinations. These provide a new reference for the screening of potential inhibitors for anticancer and antidiabetic agents.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524816","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

Synthesis of Salidroside Derivatives at C4 Position of Benzene Ring and Its Effect on Hep3B Cell Viability 苯环C4位红红草苷衍生物的合成及其对Hep3B细胞活力的影响

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-06-26 DOI: 10.1111/cbdd.70131

Juntao Wang, Zhaoqi Yang, Zili Feng, Hongbo Zhao, Congxue Duan, Yunzhi Sheng, Pengfei Du, Wang Chen, Qingjuan Chen, Dong Xiao

{"title":"Synthesis of Salidroside Derivatives at C4 Position of Benzene Ring and Its Effect on Hep3B Cell Viability","authors":"Juntao Wang, Zhaoqi Yang, Zili Feng, Hongbo Zhao, Congxue Duan, Yunzhi Sheng, Pengfei Du, Wang Chen, Qingjuan Chen, Dong Xiao","doi":"10.1111/cbdd.70131","DOIUrl":"https://doi.org/10.1111/cbdd.70131","url":null,"abstract":"<div>\u0000 \u0000 <p>Salidroside has been reported to have various pharmacological activities, including hypoxia tolerance, anti-radiation, and antitumor. In this study, we studied the antitumor activity of salidroside ether derivatives in the human hepatocellular carcinoma cell line Hep3B. We created eleven new benzyl halide derivatives called S1–S11 by modifying the phenolic hydroxyl groups at the C4 position of salidroside. The compounds were shown to inhibit tumor proliferation in the in vitro CCK-8 assay. Compounds S4, S5, S6, S7, S8, and S11 demonstrated strong inhibitory activity anti-human hepatic cancer cell Hep3B, with IC<sub>50</sub> values of 67.89, 97.55, 73.67, 57.92, 88.29, and 33.39 μM, respectively. Under the inverted microscope, compared with the blank group, after 48 h of administration, it showed obvious proliferation inhibition and apoptosis characteristics. In addition, network pharmacology predicts that these derivatives may have the effect of regulating the nervous system and protecting neuronal cells without violating Lipinski's Rule. In summary, the benzyl halide modification on the C4 phenolic hydroxyl group on the benzene ring of SAL can improve its antitumor activity, which provides ideas for the subsequent development of salidroside antitumor drugs.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492958","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

Nesfatin-1 Reduces Cholic Acid-Induced Intrahepatic Cholestasis of Pregnancy by Regulating the General Control Nonderepressible 2/Eukaryotic Initiation Factor 2α Pathway Nesfatin-1通过调节一般控制非抑制2/真核起始因子2α途径减少胆酸诱导的妊娠肝内胆汁淤积

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-06-26 DOI: 10.1111/cbdd.70147

Yong Liang, Xiaomin Wen, Zhe Sun, Yuqiong Meng, Shuhan Lv

{"title":"Nesfatin-1 Reduces Cholic Acid-Induced Intrahepatic Cholestasis of Pregnancy by Regulating the General Control Nonderepressible 2/Eukaryotic Initiation Factor 2α Pathway","authors":"Yong Liang, Xiaomin Wen, Zhe Sun, Yuqiong Meng, Shuhan Lv","doi":"10.1111/cbdd.70147","DOIUrl":"https://doi.org/10.1111/cbdd.70147","url":null,"abstract":"<div>\u0000 \u0000 <p>Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that significantly impacts pregnancy outcomes, with oxidative stress (OS) playing a crucial role in its pathogenesis. The animal model was constructed using 8–10-week-old CD-1 mice, which were administered cholic acid (CA) orally from gestational day (GD) 12–GD17 to induce placental injury. Nesfatin-1 (NF-1) was administered intraperitoneally to assess its protective effects. Our study found that NF-1 effectively attenuated placental dysfunction by reducing glucocorticoid (GC) production and boosting 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) expression, a key enzyme for GC inactivation. Furthermore, NF-1 reduced OS markers such as malondialdehyde (MDA) and reactive oxygen species (ROS) in both placental tissue and HTR8/SVneo cells. The protective effects of NF-1 were correlated with the suppression of the general control nonderepressible 2 (GCN2)/eukaryotic initiation factor 2α (eIF2α) signaling pathway, which became activated under OS conditions. Notably, halofuginone, a GCN2 agonist, abolished the beneficial effects of NF-1, further confirming the involvement of the GCN2/eIF2α pathway. These results suggest that NF-1 may serve as a potential therapeutic agent for managing ICP and related stress-induced pregnancy complications by modulating GC metabolism and mitigating OS.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492682","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

Artesunate Inhibits Myocardial Ischemia Reperfusion Injury via Downregulation of Lysine Specific Demethylase 5A 青蒿琥酯通过下调赖氨酸特异性去甲基酶5A抑制心肌缺血再灌注损伤

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-06-25 DOI: 10.1111/cbdd.70106

Yuanyuan Liu, Pengtao Zou, Yanmei Chen, Juanying Li, Qiang Liu, Qing Shangguan

{"title":"Artesunate Inhibits Myocardial Ischemia Reperfusion Injury via Downregulation of Lysine Specific Demethylase 5A","authors":"Yuanyuan Liu, Pengtao Zou, Yanmei Chen, Juanying Li, Qiang Liu, Qing Shangguan","doi":"10.1111/cbdd.70106","DOIUrl":"https://doi.org/10.1111/cbdd.70106","url":null,"abstract":"<div>\u0000 \u0000 <p>Myocardial ischemia–reperfusion (MI/R) injury can lead to heart disease. Meanwhile, Artesunate (ART) inhibits the severity of I/R-induced myocardial injury. Nevertheless, the underlying mechanism of ART in MI/R remains unclear. In vivo and in vitro experiments were performed to investigate the function of ART in MI/R. TTC, H&E, and TUNEL assays were applied for assessing myocardial injury and apoptosis. CCK-8, flow cytometry, and ELISA were applied for testing cell viability, apoptosis, and the levels of MDA, ROS, CK, and LDH, respectively. ChIP, dual luciferase assay, and RNA pull-down were performed to explore the relation among KDM5A, miR-495-3p, and FOXO1. ART dramatically attenuated I/R-induced myocardial injury in mice, and it inhibited the I/R-caused increase of ROS, MDA, CK, and LDH in mice. Additionally, ART notably alleviated hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury through inhibition of histone demethylase KDM5A, and KDM5A promoted H/R-induced injury in cardiomyocytes via downregulating miR-495-3p. Meanwhile, FOXO1 was identified as the downstream mRNA of miR-495-3p, and miR-495-3p reversed H/R-induced cardiomyocyte injury through downregulating FOXO1. Silencing of KDM5A attenuated I/R-induced myocardial injury by directly upregulating miR-495-3p in mice. ART alleviates MI/R injury via modulating KDM5A/miR-495-3p/FOXO1. Thus, this study might provide a new strategy against MI/R.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473114","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

Apelin-13 Protects Against Airway Inflammation, Oxidative Stress, and Epithelial–Mesenchymal Transition in a Chronic Asthma Model 在慢性哮喘模型中，Apelin-13保护气道炎症、氧化应激和上皮-间质转化

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-06-25 DOI: 10.1111/cbdd.70142

Huifeng Sun, Ai Wang, Nan Shi

{"title":"Apelin-13 Protects Against Airway Inflammation, Oxidative Stress, and Epithelial–Mesenchymal Transition in a Chronic Asthma Model","authors":"Huifeng Sun, Ai Wang, Nan Shi","doi":"10.1111/cbdd.70142","DOIUrl":"https://doi.org/10.1111/cbdd.70142","url":null,"abstract":"<div>\u0000 \u0000 <p>Airway inflammation, epithelial–mesenchymal transition (EMT), and airway remodeling are critical pathophysiological characteristics of chronic asthma. Apelin-13 (AP-13), a significant isoform of the apelin peptide, exhibits a wide range of physiological functions. This study aimed to investigate the potential effects and regulatory mechanisms of AP-13 in asthma. An ovalbumin (OVA)-induced murine asthma model was established to evaluate oxidative stress biomarkers, inflammatory cell infiltration (eosinophils, neutrophils, and lymphocytes), and Th2 cytokine production (IL-4, IL-5, IL-13) using enzyme-linked immunosorbent assay (ELISA). Lung histopathology was assessed by hematoxylin and eosin (H&E) staining, while epithelial–mesenchymal transition (EMT) markers were quantified through reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blot analysis, and immunohistochemistry. Our results demonstrated that AP-13 could alleviate oxidative stress, decrease the number of inflammatory cells, inhibit the release of Th2 cytokines, improve pathological changes, and suppress EMT in asthmatic mice. Collectively, our data suggest that AP-13 could be a promising therapeutic agent for the treatment of asthma.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473115","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

Relaxin-2 Alleviates Hyperoxia-Induced Acute Lung Injury in Neonatal Rats by Inhibiting TLR4/NF-κB 松弛素-2通过抑制TLR4/NF-κB减轻新生大鼠高氧诱导的急性肺损伤

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-06-21 DOI: 10.1111/cbdd.70140

Mei Yang, Qian Liu, Aili Xuan

{"title":"Relaxin-2 Alleviates Hyperoxia-Induced Acute Lung Injury in Neonatal Rats by Inhibiting TLR4/NF-κB","authors":"Mei Yang, Qian Liu, Aili Xuan","doi":"10.1111/cbdd.70140","DOIUrl":"https://doi.org/10.1111/cbdd.70140","url":null,"abstract":"<div>\u0000 \u0000 <p>Hyperoxia-induced acute lung injury (ALI) in neonates is driven by oxidative stress and inflammation. This study aims to evaluate the efficacy and underlying mechanisms of Relaxin-2 (RLX-2) in a neonatal rat model of hyperoxia-induced ALI. Neonatal Wistar rats were exposed to 90% O<sub>2</sub> for one week and treated with RLX-2 (0.5 mg/kg/day) via an osmotic pump. Methods included histopathology (hematoxylin–eosin staining), bronchoalveolar lavage fluid (BALF) analysis, Enzyme-Linked Immunosorbent Assay (ELISA) for interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α), oxidative stress markers [malondialdehyde (MDA) and superoxide dismutase (SOD)], and Western blotting for Toll-like Receptor 4 (TLR4), Nuclear Factor-kappa B (NF-κB), and Sirtuin 1 (SIRT1). Human alveolar epithelial cells (HPAEpiCs) underwent assays using Cell Counting Kit-8 (CCK-8), 2′,7′-Dichlorofluorescin diacetate (DCFH-DA), and quantitative real-time polymerase chain reaction (qRT-PCR). RLX-2 mitigated alveolar damage and inflammatory infiltration in neonatal rats with hyperoxia-induced acute lung injury. It decreased cytokine levels, reduced MDA levels, and enhanced SOD activity, thereby alleviating oxidative stress. RLX-2 suppressed TLR4/NF-κB signaling by reducing p65 and Myeloid Differentiation Primary Response 88 (MyD88) expression and upregulated SIRT1. SIRT1 silencing abolished RLX-2's effects, confirming its role in attenuating OS and inflammation. These findings demonstrated RLX-2's efficacy in neonatal ALI via SIRT1-dependent TLR4/NF-κB inhibition, highlighting therapeutic potential.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331849","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

Thienopyrimidine: Unveiling the Versatile Potential of a Promising Heterocyclic Scaffold in Drug Discovery 噻吩嘧啶：揭示一种有前途的杂环支架在药物发现中的多用途潜力

IF 3.2 4区医学

Chemical Biology & Drug Design Pub Date : 2025-06-19 DOI: 10.1111/cbdd.70146

Sahaya Nadar, Maheshkumar Borkar, Tabassum Khan

{"title":"Thienopyrimidine: Unveiling the Versatile Potential of a Promising Heterocyclic Scaffold in Drug Discovery","authors":"Sahaya Nadar, Maheshkumar Borkar, Tabassum Khan","doi":"10.1111/cbdd.70146","DOIUrl":"https://doi.org/10.1111/cbdd.70146","url":null,"abstract":"<div>\u0000 \u0000 <p>Fused pyrimidine scaffolds serve as a flexible and versatile foundational heterocycle in the field of pharmaceutical development. Thienopyrimidines are a diverse family of molecules characterized by the fusion of a thieno ring with a pyrimidine moiety, resulting in a unique scaffold with promising chemical and pharmacological properties. Thienopyrimidines exhibit multifarious features, mainly, this is due to their structural resemblance with purine bases, such as guanine and adenine. The diverse range of biological effects displayed by thienopyrimidines, such as their ability to combat bacteria, fungi, parasites, cancer and viruses, has inspired us to explore and organize their structure–activity relationship (SAR). Their intricate molecular structures enable them to interact with specific molecular targets, such as enzymes, receptors, and cellular signaling pathways, leading to their therapeutic efficacy. The presence of thienopyrimidine derivatives in several FDA-approved drugs and clinical trial candidates underscores their therapeutic potential and safety profile. The review elaborates on the primary approach for synthesis of thienopyrimidines, using thiophene derivatives or pyrimidine analogues. As our understanding of their structure–function relationships deepens, we can expect further advancements in the development of thienopyrimidine-based therapies.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323441","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