ChemMedChem最新文献_第10页

Adamantane-Appended 1,2,3-Triazole Hybrids: Synthesis and α-Glucosidase Inhibition Studies through Experimental and In Silico Approach 金刚烷附加1,2,3-三唑杂化物的合成及α-葡萄糖苷酶抑制实验研究。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-07-08 DOI: 10.1002/cmdc.202500263

Aman Ragshaniya, Subhadip Maity, Lokesh Kumar, Vivek Asati, Poojita, Avijit Kumar Paul, Jayant Sindhu, Kashmiri Lal

{"title":"Adamantane-Appended 1,2,3-Triazole Hybrids: Synthesis and α-Glucosidase Inhibition Studies through Experimental and In Silico Approach","authors":"Aman Ragshaniya, Subhadip Maity, Lokesh Kumar, Vivek Asati,  Poojita, Avijit Kumar Paul, Jayant Sindhu, Kashmiri Lal","doi":"10.1002/cmdc.202500263","DOIUrl":"10.1002/cmdc.202500263","url":null,"abstract":"In search of potent inhibitors of α-glucosidase, adamantane-appended 1,2,3-triazoles (4a-4f, 6a-6f, and 8a-8f) are synthesized using Click reaction. After establishing their structure using spectral studies, all the molecular hybrids are assayed for α-glucosidase inhibition. Compounds 6c (IC50 = 8.30 ± 0.33 μM) and 6b (IC50 = 14.0 ± 0.16 μM) exhibit promising inhibition of α-glucosidase in comparison to reference used (Acarbose, IC50 = 13.50 ± 0.32 μM). Five hybrids show better activity than precursor alkyne (IC50 = 19.57 ± 0.013 μM). The role of various covalent linkers between triazole and phenyl ring has been established using structure–activity relationship. The most probable mode of inhibition is studied by docking the most active compound 6c and Acarbose within the protein target (PDB ID: 3L4U). Compounds 2, 6c, and Acarbose show a docking score of −5.048, −6.14, and −12.118, respectively. Further, molecular dynamics simulations for 100 ns are performed to gain a detailed understanding of the complex stability. Binding energy for both the simulated complexes is calculated using MMGBSA and MMPBSA analysis, where, compound 6c exhibits a ΔGbind of −15.74 kcal mol−1. All the compounds follow Lipinski rules of five. This study paves the way for developing small-molecule-based α-glucosidase inhibitors as potential lead molecules using these hybrid frameworks.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 20","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582729","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

3′-Dehydroxypurpurogallin-4-Carboxamides as Influenza A Endonuclease Inhibitors: Synthesis, Structure–Activity Relationship Analysis, and Structural Characterization of Protein Complex 3'-去羟基嘌呤没食子素-4-羧酰胺作为甲型流感核酸内切酶抑制剂：合成、构效关系分析和蛋白质复合物的结构表征。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-07-03 DOI: 10.1002/cmdc.202500452

Michal Kráľ, Tomáš Kotačka, Róbert Reiberger, Gabriela Panýrková, Kateřina Radilová, Zuzana Osifová, Miroslav Flieger, Jan Konvalinka, Pavel Majer, Milan Kožíšek, Aleš Machara

引用次数: 0

Front Cover: (ChemMedChem 13/2025) 封面：（ChemMedChem 13/2025）

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-07-02 DOI: 10.1002/cmdc.202581301

引用次数: 0

Nonsteroidal Anti-Inflammatory Drugs as Modulators of Cation Channels: Fenamates Repurposing in Channelopathies 非甾体抗炎药作为阳离子通道调节剂：通道病变中的雌性动物再利用。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-07-02 DOI: 10.1002/cmdc.202500301

Paola Laghetti, Concetta Altamura, Simone Dell’Atti, Jean-François Desaphy, Ilaria Saltarella

{"title":"Nonsteroidal Anti-Inflammatory Drugs as Modulators of Cation Channels: Fenamates Repurposing in Channelopathies","authors":"Paola Laghetti, Concetta Altamura, Simone Dell’Atti, Jean-François Desaphy, Ilaria Saltarella","doi":"10.1002/cmdc.202500301","DOIUrl":"10.1002/cmdc.202500301","url":null,"abstract":"Cationic ion channels are transmembrane proteins that regulate the flux of cations (potassium, sodium, and calcium) across cell membrane, playing a pivotal role in many cellular functions. Disruptions of their activity can lead to the so-called genetic or acquired channelopathies, a heterogeneous group of diseases that affect multiple human systems. Fenamates, a class of nonsteroidal anti-inflammatory drugs, has recently emerged as modulators of cationic ion channels highlighting the possibility of their repurposing for the treatment ion channel-related disorders, such as channelopathies, chronic pain, epilepsy, cardiac arrhythmias, and cancers. In this review, the ability of fenamates (i.e. niflumic, flufenamic, mefenamic, meclofenamic, and tolfenamic acids) to differentially modulate the activity of cationic ion channels is described. Overall, preclinical and clinical studies suggest that fenamates represent a promising class of compounds for drug repurposing and for the development of new molecules, offering novel therapeutic opportunities for patients affected by ion channel-related disorders.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 20","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202500301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537556","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

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 3.4 4区医学

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

Yuequan Wu, Meng He, Hongtao Kong, Zhi-Hao Li, 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, Hongtao Kong, Zhi-Hao Li, Ruirui Li, Ye Qu, En Zhang","doi":"10.1002/cmdc.202500248","DOIUrl":"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 CDs, 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 CDs, many researchers find it challenging to screen precursors for the purpose of preparing CD with remarkable antibacterial abilities. It is often recommended to generate CDs directly from antibacterial agents since the process usually maintains the part qualities of its precursors during preparation. In this article, 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":"20 16","pages":""},"PeriodicalIF":3.4,"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 3.4 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":"20 16","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202500397","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":"OA","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 3.4 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":"20 16","pages":""},"PeriodicalIF":3.4,"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 3.4 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":"20 16","pages":""},"PeriodicalIF":3.4,"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 3.4 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 3.4 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":"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":"20 16","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202500185","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0