Chemical Biology & Drug Design最新文献_第2页

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

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

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