ChemMedChem最新文献_第2页

Synthesis and biological characterization of 4,4-difluoro-3(phenoxymethyl)piperidine scaffold as dopamine 4 receptor (D4R) antagonist in vitro tool compounds. 作为多巴胺4受体（D4R）拮抗剂的4,4-二氟-3（苯氧甲基）哌啶支架体外工具化合物的合成及生物学特性

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-05-29 DOI: 10.1002/cmdc.202500298

Saeedeh Saeedi, Sumaiya Nahid, Anish Vadukoot, Corey R Hopkins

引用次数: 0

Copper-induced Supramolecular Assemblies for Biomedical Applications. 生物医学应用中的铜诱导超分子组装体。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-05-28 DOI: 10.1002/cmdc.202500173

Jie Gao, Xingyao Sun, Xiangyang Zhang, Ziqi Zhao

引用次数: 0

Factors Influencing the Binding of HIV-1 Protease Inhibitors: Insights from Machine Learning Models. 影响HIV-1蛋白酶抑制剂结合的因素：来自机器学习模型的见解。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-05-28 DOI: 10.1002/cmdc.202500277

Yaffa Shalit, Inbal Tuvi-Arad

{"title":"Factors Influencing the Binding of HIV-1 Protease Inhibitors: Insights from Machine Learning Models.","authors":"Yaffa Shalit, Inbal Tuvi-Arad","doi":"10.1002/cmdc.202500277","DOIUrl":"https://doi.org/10.1002/cmdc.202500277","url":null,"abstract":"HIV-1 protease inhibitors are crucial for antiviral therapies targeting acquired immunodeficiency syndrome (AIDS). Hundreds of HIV-1 protease complexes with various ligands have been resolved and deposited in the Protein Data Bank. However, binding affinity measurements for these ligands are not always available. This gap hinders a comprehensive understanding of inhibitor efficacy. To address this challenge, machine learning (ML) models were constructed and validated based on the crystallographic coordinates of 291 HIV-1 protease-inhibitor complexes, leveraging over 2500 molecular descriptors. The models achieved accuracy scores exceeding 0.85, and applied to predict the binding affinity of 274 additional complexes for which inhibition constants were not experimentally measured. Our analysis focused on three models, each with 8-9 features, and based on KBest with Random Forest, Recursive Feature Elimination with Random Forest, and Sequential Feature Selection with Support Vector Machine. The findings revealed key predictive features, including properties of HIV-1 protease inhibitors like charge distribution, hydrogen-bonding capability, and three-dimensional topology, as well as intrinsic properties of HIV-1 protease, such as active site symmetry and flap mutations. The study highlights the contribution of a comprehensive analysis of accumulated experimental data to enhance the structural understanding of this important molecular system.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500277"},"PeriodicalIF":3.6,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155415","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

Linker Design for The Antibody Drug Conjugates: A Comprehensive Review. 抗体药物偶联物的连接设计：综述。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-05-27 DOI: 10.1002/cmdc.202500262

Yaxin Lei, Minglei Zheng, Chen Seng Ng, Peng Chen, Teck Peng Loh, Huitao Liu

{"title":"Linker Design for The Antibody Drug Conjugates: A Comprehensive Review.","authors":"Yaxin Lei, Minglei Zheng, Chen Seng Ng, Peng Chen, Teck Peng Loh, Huitao Liu","doi":"10.1002/cmdc.202500262","DOIUrl":"https://doi.org/10.1002/cmdc.202500262","url":null,"abstract":"Inspired by the \"magic bullet\" concept proposed over a century ago, antibody-drug conjugates (ADCs) were developed to enhance cancer therapy by linking monoclonal antibodies to a cytotoxic payload, aiming to overcome the limitations of conventional chemotherapy. To date, 17 ADCs have received regulatory approval for treating both hematologic and solid tumors. Despite their clinical success, developing ADCs with optimal therapeutic potential remains challenging. While selecting the appropriate antibody and cytotoxin is crucial, the linker plays a pivotal role in determining plasma stability and efficient payload release at the tumor site. Over the past decade, advances in linker technology have significantly improved the pharmacokinetics, efficacy, and toxicity profiles of ADCs. This review provides an overview of clinically validated linkers and recent innovations in linker design, focusing on drug release triggers, bioconjugation strategies, the impact of spacers on hydrophilicity, traceless drug release, and linker architecture, as well as a discussion of the bystander effect, offering insights for the rational design of next-generation ADCs.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500262"},"PeriodicalIF":3.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155416","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

Development of 2,9-Disubstituted Acridines as Topoisomerase IIα Inhibitors with Strong Anticancer Activity: Synthesis, Biological Evaluation, and In Silico Study. 具有强抗癌活性的2,9-二取代吖啶烷拓扑异构酶IIα抑制剂的研制——合成、生物学评价和硅研究。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-05-25 DOI: 10.1002/cmdc.202500267

Ladislav Janovec, Adrian Gucký, Kristína Krochtová, Radka Michalková, Katarína Kušnírová, Viktória Miškufová, Dávid Jáger, Ján Mojžiš, Mária Kožurková

{"title":"Development of 2,9-Disubstituted Acridines as Topoisomerase IIα Inhibitors with Strong Anticancer Activity: Synthesis, Biological Evaluation, and In Silico Study.","authors":"Ladislav Janovec, Adrian Gucký, Kristína Krochtová, Radka Michalková, Katarína Kušnírová, Viktória Miškufová, Dávid Jáger, Ján Mojžiš, Mária Kožurková","doi":"10.1002/cmdc.202500267","DOIUrl":"10.1002/cmdc.202500267","url":null,"abstract":"A series of 2,9-disubstituted acridines (16a-16h) is synthetized and assessed for their biological activities. The acridines feature various 9-anilino or 9-phenylalkyl substituents and are prepared via a linear sequence of six steps using commercially available starting materials. The relationship between the physicochemical properties of the 2,9-disubstituted acridines and their biological activity is studied, and the DNA binding capacities of the synthetized acridines are determined using spectroscopic (Kb 0.5-10.4 × 104 M-1) and thermal denaturation (ΔTm 4.2-9.8 °C) methods. The inhibitory potential of acridines 16a-16h toward human topoisomerase I/IIα is evaluated, and 9-phenylbutyl acridine 16h is found to inhibit human topoisomerase IIα at concentrations as low as 5 μm. Acridines 16a-16h are also subjected to in vitro screening against selected cancer cell lines; the most potent anticancer activity is observed against melanoma A2058 cell lines at IC50 values ranging from 3 to 6 μm.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e2500267"},"PeriodicalIF":3.6,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141307","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

AMPK Activation by 2'-Hydroxy-2,4,5-Trimethoxychalcone Derivatives in Podocyte Cells. 2'-羟基-2,4,5-三甲氧基查尔酮衍生物对足细胞AMPK的激活作用。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-05-24 DOI: 10.1002/cmdc.202500177

Vu-Duy Nguyen, Chatchai Muanprasat, Suchada Kaewin, Wanangkan Poolsri, Warinthorn Chavasiri

{"title":"AMPK Activation by 2'-Hydroxy-2,4,5-Trimethoxychalcone Derivatives in Podocyte Cells.","authors":"Vu-Duy Nguyen, Chatchai Muanprasat, Suchada Kaewin, Wanangkan Poolsri, Warinthorn Chavasiri","doi":"10.1002/cmdc.202500177","DOIUrl":"10.1002/cmdc.202500177","url":null,"abstract":"Activating AMP-activated protein kinase (AMPK) using chalcones has emerged as a potential therapeutic strategy for managing diabetes mellitus (DM) and diabetic nephropathy. This research focuses on discovering new chalcone derivatives with a stronger ability to stimulate AMPK in podocytes compared to 2'-hydroxychalcones 1, 2, and 3 reported from the earlier research. The results show that hydrogenated products (4-6) cannot exhibit considerably improved activity. Additionally, 2'-hydroxychalcone bearing 2,4,5-triethoxy groups on the B-ring (10) and 2,4,5-trimethoxychalcones bearing 2',4'-, 2',5'-, or 2',6'-dimethoxy groups on the A-ring (17-19) demonstrate potent AMPK activation with fold changes of 2.69, 2.36, 3.22, and 2.17, respectively, surpassing both the reference compound 1 (1.28) and metformin (1.88). The structure-activity relationship shows that inserting dimethoxy groups on the A-ring can strengthen the activity better than without inserting any group or inserting other moieties such as hydroxy, methylenedioxy, amino, trifluoromethyl, bromo, acetyl, 2,3-dihydro-1,4-dioxin ring, and benzene ring. Notably, 2,4,5-trimethoxychalcone 23 possessing 2',4',5'-trimethoxy groups, bis-chalcones 35 and 36, and tris-chalcone 37 is poorly soluble in the experiments. Compound 18 exhibits more potent activity than compounds 2 and 3 (2.48 and 2.73, respectively); therefore, it would be a promising candidate for further studies on AMPK-stimulating activity.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e2500177"},"PeriodicalIF":3.6,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136067","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 and Bio-evaluation of Quaternized Fused-β-carbolines as anti-MRSA agents. 季铵化融合β-碳胺抗mrsa药物的合成及生物评价。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-05-21 DOI: 10.1002/cmdc.202500326

Adilakshmi Vutla, Deepanshi Saxena, Rahul Maitra, Sidharth Chopra, Sanjay Batra

引用次数: 0

Synthesis and SAR Studies of Novel Oxazolyl- and Thiazolyl-indoles and Their Intermediates as Selective Antiproliferative Agents Against HL-60 Leukemia and C6 Glioma Cell Lines. 新型恶唑和噻唑吲哚及其中间体选择性抗HL-60白血病和C6胶质瘤细胞的合成和SAR研究

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-05-21 DOI: 10.1002/cmdc.202500030

Patrik Pollák, Boglárka Szele, Máté Varga, Alexandra Paszternák, Kamilla Varga, András Dancsó, Gyula Simig, Balázs Volk, Tamás Tábi, Mátyás Milen

{"title":"Synthesis and SAR Studies of Novel Oxazolyl- and Thiazolyl-indoles and Their Intermediates as Selective Antiproliferative Agents Against HL-60 Leukemia and C6 Glioma Cell Lines.","authors":"Patrik Pollák, Boglárka Szele, Máté Varga, Alexandra Paszternák, Kamilla Varga, András Dancsó, Gyula Simig, Balázs Volk, Tamás Tábi, Mátyás Milen","doi":"10.1002/cmdc.202500030","DOIUrl":"https://doi.org/10.1002/cmdc.202500030","url":null,"abstract":"1,3-Oxazole-2-carboxamides, -carbothioamides and their 1,3-thiazole analogues coupled with indoles were synthesized with promising selective antitumor effects. All compounds were prepared from tryptamine derivatives in 3-5 reaction steps including a Robinson-Gabriel cyclization to construct the oxazole or thiazole ring. The pharmacological activities of the intermediates and target compounds were assessed. Our findings revealed several novel small molecules with cancer cell-specific antiproliferative and/or cytotoxic properties, tested on HL-60 leukemia and C6 glioma cell lines. The 3-heteroarylindole target compounds demonstrated greater effectiveness compared to their acyclic intermediates. Notably, only the sulfur-containing compounds, such as thiazoles and the intermediates containing an acyclic side chain with a carbothioamide group showed significant antiproliferative properties. This activity was further enhanced by adding an extra sulfur atom, either by replacing oxazole heterocycles with thiazoles or by modifying carboxamides into carbothioamides. Additionally, the presence of a chlorine substituent at position 5 of the indole ring improved both the potency and cancer selectivity of the compounds. The synthesized novel compounds and the reported synthetic methodologies present valuable tools for drug discovery aiming at emerging pharmacological targets in the field of oncology.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500030"},"PeriodicalIF":3.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109245","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 and 64Cu-Radiolabeling Strategies of Small Organic Radioconjugates Based on the AMD070 Scaffold. 基于AMD070支架的小型有机放射缀合物的合成及64cu放射性标记策略。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-05-21 DOI: 10.1002/cmdc.202500243

Marie M Le Roy, Patricia Le Saëc, Michel Chérel, Alain Faivre-Chauvet, Raphaël Tripier, Thibault Troadec

引用次数: 0

Towards Multispecific Anti-Gp120 Artificial Antibody. 多特异性抗gp120人工抗体的研制

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-05-20 DOI: 10.1002/cmdc.202500287

Yiwei Sun, Rui Ni, Yuan-Yuan Liu, Haifang Wang, Aoneng Cao

{"title":"Towards Multispecific Anti-Gp120 Artificial Antibody.","authors":"Yiwei Sun, Rui Ni, Yuan-Yuan Liu, Haifang Wang, Aoneng Cao","doi":"10.1002/cmdc.202500287","DOIUrl":"10.1002/cmdc.202500287","url":null,"abstract":"Broadly neutralizing antibodies are potential therapeutic drugs that can recognize and block viral entry. But many viruses, such as human immunodeficiency virus (HIV), mutate rapidly and thus evade therapeutic antibodies. Multispecific antibodies and combinations of different antibodies can effectively suppress immune evasion. However, many barriers hinder the development of multispecific antibodies, and the cost of combining multiple antibodies is very high. Previously, a class of gold nanoparticle (AuNP)-based artificial antibodies, called goldbodies, were created by simply grafting the complementary-determining regions of antibodies onto AuNPs. In this study, four monospecific anti-gp120 goldbodies are created by grafting the HIV gp120-binding fragment of the CD4 protein and the CDR3 loops of three anti-gp120 antibodies onto AuNPs, respectively. Remarkably, as a first proof of concept, the study shows that all four different fragments can be grafted onto the same AuNP particle, thus creating a new type of goldbody with a very high binding affinity for gp120. In principle, this new type of goldbody costs the same as a single monospecific goldbody, but it has the potential to serve as a multispecific goldbody or a combination of multiple goldbodies.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e2500287"},"PeriodicalIF":3.6,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109247","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