ChemMedChem最新文献_第7页

A Nitroreductase-Activatable Lapachol Against Bacillus subtilis Unveils Antimicrobial Specificity 一种硝基还原酶激活的抗枯草芽孢杆菌的Lapachol揭示了抗菌特异性。

IF 3.4 4区医学

ChemMedChem Pub Date : 2026-03-13 DOI: 10.1002/cmdc.202500997

Ivonne R. Lopez-Miranda, Tianyi Ma, Joshua N. Milstein, Andrew A. Beharry

引用次数: 0

Quinic Acid and Synthetic Derivatives in Medicinal Chemistry 药物化学中的奎宁酸及其合成衍生物。

IF 3.4 4区医学

ChemMedChem Pub Date : 2026-03-13 DOI: 10.1002/cmdc.202500976

Iago C. Vogel, Manuel J. Verganista, Nuno R. Candeias

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Mechanism and Molecular Design Principles of Cationic Surfactants: From Charge-Driven Membrane Interactions to Next-Generation Quaternary Ammonium Compounds 阳离子表面活性剂的机理和分子设计原则：从电荷驱动的膜相互作用到下一代季铵化合物。

IF 3.4 4区医学

ChemMedChem Pub Date : 2026-03-13 DOI: 10.1002/cmdc.202501104

Natalie Hanheiser, Yuhang Jiang, Chuanxiong Nie, Rainer Haag

{"title":"Mechanism and Molecular Design Principles of Cationic Surfactants: From Charge-Driven Membrane Interactions to Next-Generation Quaternary Ammonium Compounds","authors":"Natalie Hanheiser, Yuhang Jiang, Chuanxiong Nie, Rainer Haag","doi":"10.1002/cmdc.202501104","DOIUrl":"10.1002/cmdc.202501104","url":null,"abstract":"Cationic surfactants, in particular quaternary ammonium compounds (QACs), represent one of the most relevant and broadly applied classes of antiseptics. Their antimicrobial activity arises from electrostatic interactions with microbial membranes, resulting in rapid disruption of the membrane structure. In this review, we summarize currently described mechanistic insights into the membrane active behavior of QACs, thereby focusing on the interplay between molecular architecture, supramolecular organization and antimicrobial efficacy. Key structure activity relationships (SARs) are discussed, including the role of the hydrophobic tail length, spacer design, charge density and distribution, and counterion effects. Addressing challenges such as antimicrobial resistance and biocompatibility requires a detailed understanding of SARs and the mechanism behind resistance development. Therefore, we further highlight emerging concepts such as cleavable linkers, hybrid systems integrating metal, peptide or photodynamic modalities, supramolecular aggregates, and the integration of biodegradable materials for the design of surfactants capable of overcoming bacterial resistance and tuning selectivity toward bacterial cells. This review provides an updated framework for developing next-generation QACs that preserve antimicrobial potency while minimizing toxicity and the evolution of resistant microbial populations.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12987642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454948","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

Front Cover: pH-Responsive Isoprenoid-Antitumoral Polymer Conjugates for Superior Drug Loading via Self-Assembly and Endosomal-Targeted Anticancer Activity (ChemMedChem 5/2026) 封面：ph响应性异戊二烯类抗肿瘤聚合物偶联物，通过自组装和内体靶向抗癌活性获得更好的药物负载（ChemMedChem 5/2026）

IF 3.4 4区医学

ChemMedChem Pub Date : 2026-03-13 DOI: 10.1002/cmdc.70264

Camilla Passi, Tobias Neu, Nicole Schneider-Daum, Claus-Michael Lehr, Marc Schneider, Sangeun Lee

引用次数: 0

Synthesis, Biological Evaluation, and Theoretical Study of Indenoquinolinylphosphine Oxide Derivatives as Topoisomerase 1 Inhibitors and Antiproliferative Agents 环氧吲哚喹啉膦衍生物拓扑异构酶1抑制剂和抗增殖剂的合成、生物学评价和理论研究。

IF 3.4 4区医学

ChemMedChem Pub Date : 2026-03-13 DOI: 10.1002/cmdc.202500751

Alba Rodriguez, Elena Formoso, Birgitta R. Knudsen, Cinzia Tesauro, Maria Fuertes, Concepcion Alonso

{"title":"Synthesis, Biological Evaluation, and Theoretical Study of Indenoquinolinylphosphine Oxide Derivatives as Topoisomerase 1 Inhibitors and Antiproliferative Agents","authors":"Alba Rodriguez, Elena Formoso, Birgitta R. Knudsen, Cinzia Tesauro, Maria Fuertes, Concepcion Alonso","doi":"10.1002/cmdc.202500751","DOIUrl":"10.1002/cmdc.202500751","url":null,"abstract":"The topoisomerase 1 (TOP1) enzymatic inhibition and antiproliferative activity of phosphorated indenoquinoline derivatives were investigated. First, the preparation of new hybrid quinoline and tetrahydroquinoline structures with a phosphine oxide group was performed by a two-step Povarov type [4 + 2]-cycloaddition reaction between the corresponding phosphorated aldimines with indene in the presence of BF3·Et2O, affording corresponding 1,2,3,4-tetrahydroindeno[2,1-c]quinolinylphosphine oxides 9, 7H-indeno[2,1-c]quinolinylphosphine oxides 10 and 7-oxoindeno[2,1-c]quinolinylphosphine oxides 11 with good yields. The synthesized derivatives were evaluated as TOP1 inhibitors, showing that some derivatives (9f, 9g, 9l, and 11m) show better or similar activity to the reference compound (CPT) at 1 min. The synthesized derivatives were screened for their antiproliferative activity in different cancerous cell lines, and all of them present a higher selective cytotoxicity in the human lung adenocarcinoma cell line (A549), than in the others. In contrast, almost none of the synthesized phosphorated compounds exhibited antiproliferative activity toward nonmalignant lung fibroblasts MCR5. These results suggest that phosphine oxide-substituted quinoline derivatives have important properties as TOP1 inhibitors and show an interesting cytotoxicity against six different cancerous cell lines.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12987641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454974","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

Modulation of Tau Protein Neurotoxic Hallmarks by Novel σ1R Agonists/HDAC Inhibitor Dual-Acting Compounds 新型σ1R激动剂/HDAC抑制剂双作用化合物对Tau蛋白神经毒性特征的调节。

IF 3.4 4区医学

ChemMedChem Pub Date : 2026-03-13 DOI: 10.1002/cmdc.202500922

Antonino N. Fallica, Carla Barbaraci, M. Carmen Ruiz-Cantero, Arianna Scarlatti, Alessandro Coco, Giorgia Giordano, Alfonsina La Mantia, Orazio Prezzavento, Antonio Di Stefano, Ivana Cacciatore, Giacomo Siano, Antonino Cattaneo, Lorella Pasquinucci, Enrique J. Cobos, Cristina Di Primio, Emanuele Amata, Agostino Marrazzo

{"title":"Modulation of Tau Protein Neurotoxic Hallmarks by Novel σ1R Agonists/HDAC Inhibitor Dual-Acting Compounds","authors":"Antonino N. Fallica, Carla Barbaraci, M. Carmen Ruiz-Cantero, Arianna Scarlatti, Alessandro Coco, Giorgia Giordano, Alfonsina La Mantia, Orazio Prezzavento, Antonio Di Stefano, Ivana Cacciatore, Giacomo Siano, Antonino Cattaneo, Lorella Pasquinucci, Enrique J. Cobos, Cristina Di Primio, Emanuele Amata, Agostino Marrazzo","doi":"10.1002/cmdc.202500922","DOIUrl":"10.1002/cmdc.202500922","url":null,"abstract":"Neurodegenerative diseases, like Alzheimer's disease (AD), are characterized by the accumulation of tau aggregates, leading to neuronal dysfunction and cognitive decline. This study explores the development of dual-acting compounds combining sigma-1 receptor (σ1R) agonists and histone deacetylase inhibitors (HDACi) to target these pathological mechanisms. Compounds 2d and 3a demonstrated high affinity for σ1R and significantly reduced tau aggregation and phosphorylation in vitro, notably at the AT8 epitope. These dual-acting compounds destabilized tau aggregates, increased tau solubility, and showed favorable pharmacokinetic properties, with compound 2d exhibiting enhanced chemical stability and longer half-life than 3a. In vivo, both compounds confirmed a σ1R agonist profile by reversing the effect of the σ1R antagonist BD-1063. This dual-action approach, acting on both HDAC and σ1R pathways, holds significant potential for treating tauopathies. While further optimization and clinical evaluation are needed, these findings provide a strong foundation for the continued development of multimodal therapies for neurodegenerative diseases treatment.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12987640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454918","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

Discovery of Pyrazolo[5,1-b]quinazoline Tethered 1,2,3-Triazole Analogs as Potential Antioxidant Agents: Design, Synthesis, Biological Evaluation, and In Silico Insights 吡唑啉[5,1-b]喹唑啉系接1,2,3-三唑类似物作为潜在抗氧化剂的发现：设计、合成、生物学评价及其在硅中的应用。

IF 3.4 4区医学

ChemMedChem Pub Date : 2026-03-12 DOI: 10.1002/cmdc.202500683

Reena C. Patel, Kaushal B. Parmar, Manish P. Patel

{"title":"Discovery of Pyrazolo[5,1-b]quinazoline Tethered 1,2,3-Triazole Analogs as Potential Antioxidant Agents: Design, Synthesis, Biological Evaluation, and In Silico Insights","authors":"Reena C. Patel, Kaushal B. Parmar, Manish P. Patel","doi":"10.1002/cmdc.202500683","DOIUrl":"10.1002/cmdc.202500683","url":null,"abstract":"This article seeks to develop new antioxidant agents to address the rising prevalence of oxidative stress-associated disorders. This research outlines a high-yielding synthetic approach to functionalized pyrazolo[5,1-b]quinazoline tethered 1,2,3-triazole derivatives 7(a-x) using L-proline as a catalyst under microwave irradiation. The synthesized compounds were evaluated for their in vitro antioxidant activity using 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical as well as hydrogen peroxide (H2O2) scavenging assays. In all assays, compounds 7a, 7b, 7c, 7d, 7m, 7n, 7o, and 7p exhibited significantly greater antioxidant activity compared to the reference standard, ascorbic acid. Molecular docking study reinforced the experimental findings, showing that the compounds engage in multiple binding interactions within the active sites of both enzymes. Additionally, density functional theory (DFT) analysis was also performed to examine the electronic and molecular properties of the compounds, revealing strong agreement between theoretical predictions and experimental results. Overall, the results highlight these derivatives as promising lead candidates for antioxidant drug development, supported by robust evidence from molecular docking and DFT analyses.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147441980","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 Expanded CUG and CTG Repeats as a Therapeutic Approach for Myotonic Dystrophy Type 1 (DM1) 靶向CUG和CTG重复扩增作为1型肌强直性营养不良（DM1）的治疗方法

IF 3.4 4区医学

ChemMedChem Pub Date : 2026-03-09 DOI: 10.1002/cmdc.202500958

Camille Richagneux, Anton Granzhan

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A Novel Synthetic Route for Lysine-Specific Demethylase 1-Targeting Compounds: CC-90011 and MS9117 赖氨酸特异性去甲基酶1靶向化合物CC-90011和MS9117的合成新途径

IF 3.4 4区医学

ChemMedChem Pub Date : 2026-03-03 DOI: 10.1002/cmdc.202501081

Jingying Wang, Yuying Li, Jingya Zhang, Wenwen Wang, Jianghong Tan, Jingxing Zheng, Shuyi Jiang, Sidi Cheng, Bin Yu

引用次数: 0

Responsive Nanomolecular Probes for Evolving Liver Diseases: Technological Revolutions and Challenges 响应性纳米分子探针用于不断演变的肝脏疾病：技术革命和挑战。

IF 3.4 4区医学

ChemMedChem Pub Date : 2026-03-03 DOI: 10.1002/cmdc.202501026

Guozhu Yang, Chunshu Pan, Pengli Zhang, Fengzheng Tang, Liangchen Luo, Pingting Luo, Jianjun Zheng, Jingfeng Zhang, Aiguo Wu, Tianxiang Chen

{"title":"Responsive Nanomolecular Probes for Evolving Liver Diseases: Technological Revolutions and Challenges","authors":"Guozhu Yang, Chunshu Pan, Pengli Zhang, Fengzheng Tang, Liangchen Luo, Pingting Luo, Jianjun Zheng, Jingfeng Zhang, Aiguo Wu, Tianxiang Chen","doi":"10.1002/cmdc.202501026","DOIUrl":"10.1002/cmdc.202501026","url":null,"abstract":"Early diagnosis of liver diseases has long faced serious challenges such as insufficient sensitivity, low specificity and difficulty in revealing molecular lesion information by conventional imaging methods. With the rapid development of nanoscience, nanomolecular probes exhibit tuneable structure, modifiable surface and excellent biocompatibility, and their responsive properties have gradually become an ideal medium for connecting molecular pathological changes and image visualisation. This review reveals that functionalised nanoprobes responsive to disease microenvironment-specific signals (e.g., reactive oxygen species, enzymes, pH, metal ions, etc.) can enable the visualisation and tracking of molecular events in liver diseases, thereby promoting the shift of diagnostic paradigm from traditional morphological assessment to precise identification at the functional and molecular levels. This article not only systematically reviews the latest application progress of responsive nanoprobes in liver disease diagnosis, but also demonstrates their great potential to shift the diagnostic paradigm from macro-anatomy to micro-molecule. At the same time, this article presents an in-depth analysis of the key bottlenecks in the clinical translation process, thereby outlining directions for the rational design of next-generation intelligent nano-diagnostic tools. Collectively, this work offers new insights and strategies to accelerate the early and precise diagnosis and treatment of liver diseases.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 5","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347163","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