ChemMedChem最新文献_第2页

Recent Progress of Antibacterial Carbon Dots Prepared from Marketed Small Molecule Antibacterial Drugs. 市售小分子抗菌药物制备抗菌碳点的研究进展。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-06-28 DOI: 10.1002/cmdc.202500248

Yuequan Wu, Meng He, Zhi-Hao Li, Hongtao Kong, Ruirui Li, Ye Qu, En Zhang

{"title":"Recent Progress of Antibacterial Carbon Dots Prepared from Marketed Small Molecule Antibacterial Drugs.","authors":"Yuequan Wu, Meng He, Zhi-Hao Li, Hongtao Kong, Ruirui Li, Ye Qu, En Zhang","doi":"10.1002/cmdc.202500248","DOIUrl":"https://doi.org/10.1002/cmdc.202500248","url":null,"abstract":"The massive consumption of antibiotics leads to antibiotic resistance, which is a major concern in the global health crisis. Therefore, the development of non-antibiotic antibacterial drugs occurs simultaneously with the development of antibiotics. Nanomaterial applications in antibacterial research are currently expanding. Carbon dots, termed as CD, are a novel class of nanomaterials that have garnered a lot of interest. Antibacterial CD has many outstanding characteristics, such as high biocompatibility, easy surface modification, excellent optical properties, an extensive precursor source, and a small particle size (1-10 nm). Although there are many potential sources of CD, many researchers find it challenging to screen precursors for the purpose of preparing CD with remarkable antibacterial abilities. It is often recommended to generate CD directly from antibacterial agents since the process usually maintains the part qualities of its precursors during preparation. In this paper, CDs prepared by marketed small molecule antibacterial drugs were selected as our topic. Their characteristics of preparation, biocompatibility and antibacterial activity were discussed. This review summarizes the antibacterial CDs prepared from aminoglycosides, β-lactams, quinolones, antituberculosis drugs, and nitroimidazole antibacterial drugs as precursors. Then the advantages and mechanisms of CDs, the existing problems and future possibilities of antibacterial CDs were also explored.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202500248"},"PeriodicalIF":3.6,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery of a Phenylalanine-Derived Natural Compound as a Potential Dual Inhibitor of MDM2 and MDMX. 苯丙氨酸衍生的天然化合物作为MDM2和MDMX的潜在双重抑制剂的发现。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-06-27 DOI: 10.1002/cmdc.202500397

Ja Young Cho, Sanghwa Park, Taejung Kim, Junghye Eom, Jung-Rae Rho, Hyoung-Woo Bai

{"title":"Discovery of a Phenylalanine-Derived Natural Compound as a Potential Dual Inhibitor of MDM2 and MDMX.","authors":"Ja Young Cho, Sanghwa Park, Taejung Kim, Junghye Eom, Jung-Rae Rho, Hyoung-Woo Bai","doi":"10.1002/cmdc.202500397","DOIUrl":"10.1002/cmdc.202500397","url":null,"abstract":"Dual inhibition of the negative p53 regulators MDM2 and MDMX has emerged as an effective strategy in p53-based anticancer therapy. However, dual inhibitors are limited, and many inhibitors exhibit poor pharmacokinetic properties and fast dissociation kinetics. Among newly identified microbial metabolites, the novel phenylalanine-derived compound P5 isolated from Micromonospora sp. MS-62 (FBCC-B8445) exhibits inhibitory activity against both MDM2 and MDMX. The binding of P5 to MDM2 and MDMX is demonstrated by surface plasmon resonance, which reveals nanomolar-level affinity and slow dissociation kinetics (KD = 46 nM for MDM2; 576 nM for MDMX). This dual inhibitory activity was further supported by molecular docking, which reveals binding of P5 to the p53-binding pockets of both MDM2 and MDMX through extensive noncovalent interactions. In cell-based assays, P5 reduced cancer cell viability across several human cell lines. Furthermore, in silico analysis indicates favorable pharmacokinetic properties, including gastrointestinal absorption, blood-brain barrier permeability, and compliance with Lipinski's and Veber's criteria. P5 combines dual-target engagement with binding persistence and favorable pharmacokinetic characteristics, addressing limitations of earlier inhibitors. P5 is a potential lead compound for the development of MDM2/MDMX-targeted anticancer agents.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e2500397"},"PeriodicalIF":3.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504288","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

Design, Synthesis, Antimicrobial, and Antimalarial Evaluation of Quinoline Hydrazone Derivatives: Insight through Density Functional Theory Analysis, Molecular Docking, and Absorption, Distribution, Metabolism, Excretion, and Toxicity Predictions. 喹啉腙衍生物的设计、合成、抗菌和抗疟评价：通过DFT分析、分子对接和ADMET预测的见解。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-06-26 DOI: 10.1002/cmdc.202500283

Sangeeta Verma, Sukhbir Lal, Rakesh Narang, Ritu Badal, Raman Saini, Somdutt Mujwar

{"title":"Design, Synthesis, Antimicrobial, and Antimalarial Evaluation of Quinoline Hydrazone Derivatives: Insight through Density Functional Theory Analysis, Molecular Docking, and Absorption, Distribution, Metabolism, Excretion, and Toxicity Predictions.","authors":"Sangeeta Verma, Sukhbir Lal, Rakesh Narang, Ritu Badal, Raman Saini, Somdutt Mujwar","doi":"10.1002/cmdc.202500283","DOIUrl":"10.1002/cmdc.202500283","url":null,"abstract":"Antimicrobial and antimalarial resistance are the major global health threats and indicating to develop novel targeted molecules to overcome the resistance problem. In this concern, in the present study, some quinoline hydrazone derivatives (6a-6o) have been synthesized and evaluated as antimicrobial and antimalarial agents. Compound 6o is observed to be the most active and presented equipotent antibacterial activity (MIC = 6.25 μg mL-1) as the standard drug ofloxacin against Escherichia coli and Pseudomonas aeruginosa. Antimalarial activity showed that compound 6g exhibits maximum inhibitory action (IC50 = 0.56 μg mL-1) and is significant in contrast to standard drugs chloroquine (IC50 = 0.020 μg mL-1) and quinine (IC50 = 0.268 μg mL-1) against Plasmodium falciparum. Density functional theory analysis evaluates the chemical reactivity of molecular orbitals of the most active compounds 6g and 6o. Furthermore, molecular docking study showed that most active antimalarial (6g) and antimicrobial (6o) compounds exhibit potent interactions with targeted enzymes (lactate dehydrogenase and dihydrofolate reductase (DHFR), respectively). In silico drug-likeness parameters and absorption, distribution, metabolism, excretion, and toxicity study indicate that all the synthesized derivatives followed the acceptance criteria. The present study emphasizes that compounds 6g (antimalarial) and 6o (antimicrobial) can be developed as novel inhibitors against lactate dehydrogenase and DHFR enzyme, respectively, on the completion of drug discovery approaches.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e2500283"},"PeriodicalIF":3.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493268","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 Characterization of Sulfonamide-Imidazole Hybrids with In Vitro Antiproliferative Activity against Anthracycline-Sensitive and Resistant H69 Small Cell Lung Cancer Cells. 对蒽环类药物敏感和耐药的H69 SCLC细胞具有体外抗增殖活性的磺胺类-咪唑复合物的合成和表征。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-06-26 DOI: 10.1002/cmdc.202500260

Valdas Vainauskas, Povilas Kavaliauskas, Birutė Grybaitė, Vidmantas Petraitis, Rūta Petraitienė, Ramunė Grigalevičiūtė, Rūta Prakapaitė, Waldo Acevedo, Vytautas Mickevičius

{"title":"Synthesis and Characterization of Sulfonamide-Imidazole Hybrids with In Vitro Antiproliferative Activity against Anthracycline-Sensitive and Resistant H69 Small Cell Lung Cancer Cells.","authors":"Valdas Vainauskas, Povilas Kavaliauskas, Birutė Grybaitė, Vidmantas Petraitis, Rūta Petraitienė, Ramunė Grigalevičiūtė, Rūta Prakapaitė, Waldo Acevedo, Vytautas Mickevičius","doi":"10.1002/cmdc.202500260","DOIUrl":"10.1002/cmdc.202500260","url":null,"abstract":"A series of novel sulfonamide-imidazole hybrid derivatives are synthesized, and their antiproliferative properties are evaluated. The global challenge of cancer, highlighted by rising morbidity and mortality rates, is further intensified by the increasing prevalence of drug-resistant cancer cells. Targeting the molecular mechanisms underlying therapeutic resistance is crucial for the development of innovative treatment strategies to improve clinical outcomes. Herein, the in vitro antiproliferative activity of novel sulfonamide derivatives, which exhibited significant low micromolar cytotoxicity against H69 human lung carcinoma cells and anthracycline-resistant H69AR cells compared to untreated controls (p < 0.05), is synthesized and characterized. The most promising compounds (11e, 11g, 11h, 12) also demonstrate cytotoxic activity against A549 human lung adenocarcinoma cells. Molecular docking studies predict that compound 11e interacts with tropomyosin receptor kinase A (TRKA) and mesenchymal-epithelial transition factor (c-MET) at conserved binding sites also targeted by FDA-approved inhibitors. These findings suggest that the novel sulfonamide derivatives, particularly compound 11e, may serve as promising antiproliferative candidates targeting TRKA and c-MET, potentially contributing to strategies aimed at overcoming drug resistance. Moreover, compound 11e can serve as a structural scaffold for future hit-to-lead optimization efforts.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e2500260"},"PeriodicalIF":3.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493269","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

Bioresponsive Hyaluronic Acid-Based Hydrogel Inhibits Matrix Metalloproteinase-2 in Glioblastoma Microenvironment. 生物反应性透明质酸基水凝胶抑制基质金属蛋白酶-2在胶质母细胞瘤微环境中的作用。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-06-24 DOI: 10.1002/cmdc.202401040

Federica Barbugian, Domenico Salerno, Elisa Ballarini, Luca Crippa, Oscar Francesconi, Francesco Mantegazza, Guido Cavaletti, Stefano Roelens, Gemma Leone, Simone Pepi, Luigi Talarico, Agnese Magnani, Cristina Nativi, Laura Russo

引用次数: 0

Targeting Ubiquitin-Specific Protease 7 with Novel 5-Amino-Pyrazole Inhibitors: Design, Synthesis, and Biological Evaluation. 靶向泛素特异性蛋白酶7的新型5-氨基吡唑抑制剂：设计、合成和生物学评价。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-06-24 DOI: 10.1002/cmdc.202500185

Matteo Lusardi, Elva Morretta, Andrea Spallarossa, Maria Chiara Monti, Camillo Rosano, Erika Iervasi, Marco Ponassi, Matteo Mori, Fiorella Meneghetti, Chiara Brullo

{"title":"Targeting Ubiquitin-Specific Protease 7 with Novel 5-Amino-Pyrazole Inhibitors: Design, Synthesis, and Biological Evaluation.","authors":"Matteo Lusardi, Elva Morretta, Andrea Spallarossa, Maria Chiara Monti, Camillo Rosano, Erika Iervasi, Marco Ponassi, Matteo Mori, Fiorella Meneghetti, Chiara Brullo","doi":"10.1002/cmdc.202500185","DOIUrl":"https://doi.org/10.1002/cmdc.202500185","url":null,"abstract":"To further extend the structure-activity relationships (SARs) of the previously published ubiquitin-specific protease 7 (USP-7) inhibitor STIRUR-41, a small library of 5-aminopyrazoles 1a-d and 2a-d is designed and synthesized. The chemical identity of the desired structure is confirmed by nuclear magnetic resonance and single crystal X-ray diffraction analyses. All novel derivatives are tested as potential USP-7 inhibitors and compounds 1a-d block enzyme activity in a dose-dependent manner and with lower IC50 values compared to the lead compound STIRUR-41. Notably, 1d, bearing a meta-trifluoromethylphenyl group linked to the carbamate moiety, proved to be the most active candidate. Conversely, compounds belonging to series 2, which possess greater steric hindrance, exhibit no activity. The most effective compounds of series 1 are noncytotoxic across a panel of tumor and normal cell lines at 10 μM concentration. For the most active compound 1d, a parallel artificial membrane permeability assay is also performed, as well as docking and molecular dynamics simulations.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e2500185"},"PeriodicalIF":3.6,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482695","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

The Role of Five-Membered Aromatic Rings Containing N and O in Modulating Bile Acid Receptors: An Overview. 含N和O的五元芳香环在胆汁酸受体调控中的作用综述。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-06-19 DOI: 10.1002/cmdc.202500405

Claudia Finamore, Carmen Festa, Rosa Barbato, Stefano Fiorucci, Angela Zampella, Simona De Marino

{"title":"The Role of Five-Membered Aromatic Rings Containing N and O in Modulating Bile Acid Receptors: An Overview.","authors":"Claudia Finamore, Carmen Festa, Rosa Barbato, Stefano Fiorucci, Angela Zampella, Simona De Marino","doi":"10.1002/cmdc.202500405","DOIUrl":"10.1002/cmdc.202500405","url":null,"abstract":"Over the past decades, extensive scientific research in the fields of chemistry and pharmaceutical chemistry has led to the synthesis and study of numerous chemical compounds with diverse therapeutic applications. Many of these compounds feature heterocyclic aromatic structures, including four-, five-, and six-membered rings. Among them, five-membered heteroaromatic rings have garnered particular attention in medicinal chemistry due to their favorable properties, such as enhanced metabolic stability, solubility, and bioavailability, key attributes for the development of effective drugs. The distinctive physicochemical properties and biological activities of five-membered heterocycles have established them as vital structural motifs in numerous clinically effective drugs. These heterocyclic compounds play a crucial role in the design of therapeutic agents, including those targeting bile acid receptors. Bile acid receptor modulators, activated by endogenous bile acids, offer promising potential in treating a variety of metabolic and enterohepatic disorders, such as dyslipidemia, diabetes, cholestasis, and inflammatory bowel disease. This review aims to provide an up-to-date overview of aromatic five-membered nitrogen- and oxygen-containing heterocycles, focusing on their role as bile acid receptor modulators, particularly farnesoid X receptor and G protein-coupled bile acid receptor 1. These receptors are clinically validated targets for the treatment of metabolic disorders and nonalcoholic steatohepatitis.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e2500405"},"PeriodicalIF":3.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323963","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

Balinatunfib: A Clinical Oral Small Molecule TNFα Inhibitor Balinatunfib：临床口服小分子TNFα抑制剂。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-06-19 DOI: 10.1002/cmdc.202500258

Alexander Dömling, Tad A. Holak

{"title":"Balinatunfib: A Clinical Oral Small Molecule TNFα Inhibitor","authors":"Alexander Dömling, Tad A. Holak","doi":"10.1002/cmdc.202500258","DOIUrl":"10.1002/cmdc.202500258","url":null,"abstract":"Most diseases are accompanied by an inflammatory response, making effective pharmacological control highly desirable. Tumor necrosis factor alpha (TNFα) is a key cytokine driving inflammatory and autoimmune diseases, such as rheumatoid arthritis and inflammatory bowel disease. Although biological TNFα inhibitors revolutionized treatment, they have drawbacks including lacking blood–brain barrier penetration, parenteral administration, and immunogenicity. Recent studies highlight the potential of small-molecule approaches to target TNFα by stabilizing an asymmetrical, receptor-incompetent trimer conformation. Balinatunfib (also known as SAR441566) is an orally available small molecule designed to exploit this mechanism, thereby preventing TNFα from effectively binding to its receptors. In preclinical models, balinatunfib reduces inflammation comparably to biologic therapies, yet avoids the complexities of large protein therapeutics. This allosteric strategy involves capturing a sampled but distorted state of TNFα, thereby blocking receptor clustering and downstream proinflammatory signaling. The oral route of administration confers practical advantages in terms of patient compliance and could facilitate drug access to sites traditionally less amenable to biologics, such as the central nervous system. By demonstrating that small molecules can achieve high-affinity, conformation-based inhibition of TNFα, balinatunfib, and related compounds may result in a new area of orally administered therapies that advance the management of TNFα-mediated diseases.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 14","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202500258","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332194","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

Proton first: rationalizing a proton transfer in a protein-fragment complex. 质子优先：使蛋白质片段复合物中的质子转移合理化。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-06-18 DOI: 10.1002/cmdc.202500244

Helge Vatheuer, Jonas Paulus, Lisa Johannknecht, Gerald Keller, Rebecca Maria Ziora, Lukas Stelzl, Paul Czodrowski

引用次数: 0

Front Cover: (ChemMedChem 12/2025) 封面：（ChemMedChem 12/2025）

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-06-17 DOI: 10.1002/cmdc.202581201

引用次数: 0