ChemMedChem最新文献_第4页

A Blood–Brain Barrier-Permeable Guanylhydrazone Analogue of the ASIC3 Activator GMQ Inhibits Human Glioblastoma Stem Cell Growth In Vitro ASIC3激活物GMQ的血脑屏障通透性鸟酰腙类似物体外抑制人胶质母细胞瘤干细胞生长

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-09-23 DOI: 10.1002/cmdc.70438

Leonardo Maiorana, Nicoletta Collura, Andrea Gotti, Giulia De Leonardis, Greta Donati, Alice Maiocchi, Luciana Marinelli, Andrea Menegon, Pierfausto Seneci

{"title":"A Blood–Brain Barrier-Permeable Guanylhydrazone Analogue of the ASIC3 Activator GMQ Inhibits Human Glioblastoma Stem Cell Growth In Vitro","authors":"Leonardo Maiorana, Nicoletta Collura, Andrea Gotti, Giulia De Leonardis, Greta Donati, Alice Maiocchi, Luciana Marinelli, Andrea Menegon, Pierfausto Seneci","doi":"10.1002/cmdc.70438","DOIUrl":"10.1002/cmdc.70438","url":null,"abstract":"The acid-sensing ion channel 3 (ASIC3) is a neuronal voltage-insensitive Na+ channel located in the peripheral nervous system (PNS) and activated by extracellular H+, that is dysregulated in peripheral neuropathic pain. ASIC3 was found in stem cells of central nervous system (CNS)–located glioblastoma multiforme (GBM CSCs), and its chronic activation kills dysfunctional GBM CSCs without any effect on ASIC3-lacking CNS tissues. We rationally designed and synthesized blood–brain barrier (BBB)–compliant analogues of GMQ, a known guanidyl quinazoline ASIC3 activator; we replaced its guanidine group with a guanyl hydrazone (GH) and carried out scaffold substitutions and other structural variations in 16 GMQ analogues to establish a structure–activity relationship (SAR). Our more potent GH analogue 1a showed specific activity against GBM CSC neurospheres, coupled with a better safety profile on mammalian nontumor cells and a better brain-to-plasma ratio compared with GMQ. Such results provide valuable insights for further structural optimization of heteroaryl GHs as ASIC3 modulators.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 18","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.70438","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029418","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

A Multistage Computational Framework for Early Prioritization of Natural Anti-Inflammatory Candidates From Diverse Chemical Spaces 从不同的化学空间的天然抗炎候选物的早期优先排序的多阶段计算框架。

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-09-21 DOI: 10.1002/cmdc.70497

Huynh Anh Duy, Tarapong Srisongkram

{"title":"A Multistage Computational Framework for Early Prioritization of Natural Anti-Inflammatory Candidates From Diverse Chemical Spaces","authors":"Huynh Anh Duy, Tarapong Srisongkram","doi":"10.1002/cmdc.70497","DOIUrl":"10.1002/cmdc.70497","url":null,"abstract":"Identifying safe and effective anti-inflammatory agents is challenging, especially given the adverse effects of long-term conventional therapies. Here, we present a multistage computational framework to prioritize early natural compounds with potential anti-inflammatory activity across diverse chemical spaces. The proposed workflow integrates machine learning, consensus prediction, drug-likeness evaluation, synthetic accessibility assessment, toxicity prediction, and molecular docking to enable stepwise refinement of candidate selection. Six predictive models were developed and evaluated with gold-standard metrics, all showing consistent performance with accuracies, AUROCs, and AUPRCs above 0.8. A consensus strategy was used to reduce model variability and improve prediction reliability. SHAP analysis identified structural scaffolds associated with predicted anti-inflammatory activity, providing interpretability for compound prioritization. Sequential filtering selected compounds that met predefined criteria for drug-likeness, synthetic feasibility, and predicted safety profiles. Application of the framework to the NPASS database yielded 20 prioritized natural products, of which 17 candidates were further selected based on molecular docking analysis, exhibiting predicted binding affinities of <−7 kcal/mol. This framework was deployed on a web server, CAIP (https://caip-predictor.streamlit.app/), enabling rapid prediction and preliminary virtual screening of novel compounds. In total, the proposed framework offers a computational approach to systematically support the prioritization of anti-inflammatory candidate molecules.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 18","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015088","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

Potent Caspase-1 Antagonists From Dihydropyridine Derivatives: In Vitro Fluorescence Assays and Cell Imaging 来自二氢吡啶衍生物的强效Caspase-1拮抗剂：体外荧光测定和细胞成像。

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-09-20 DOI: 10.1002/cmdc.70496

Kittiporn Nakprasit, Thitiporn Pattarakankul, Tanapat Palaga, Thanapon Charoenwongpaiboon, Waroton Paisuwan, Kavisara Srithadindang, Rachanon Eakprachasin, Islah Muttaqin, Pattraporn Chobpradit, Sucharat Sanongkiet, Mongkol Sukwattanasinitt, Chanakan Tongsook, Anawat Ajavakom

{"title":"Potent Caspase-1 Antagonists From Dihydropyridine Derivatives: In Vitro Fluorescence Assays and Cell Imaging","authors":"Kittiporn Nakprasit, Thitiporn Pattarakankul, Tanapat Palaga, Thanapon Charoenwongpaiboon, Waroton Paisuwan, Kavisara Srithadindang, Rachanon Eakprachasin, Islah Muttaqin, Pattraporn Chobpradit, Sucharat Sanongkiet, Mongkol Sukwattanasinitt, Chanakan Tongsook, Anawat Ajavakom","doi":"10.1002/cmdc.70496","DOIUrl":"10.1002/cmdc.70496","url":null,"abstract":"Caspase-1 is a key marker in pyroptosis and inflammation, playing a central role in the pathogenesis of various acute and chronic inflammatory diseases. While some caspase-1 sensing and inhibition studies have been reported, the use of DHPs for these applications remains unexplored. To address this challenge, a novel fluorescent compound, zWEHD-NH-DHP, was synthesized and subsequently developed as a real-time caspase-1 detection in vitro and in cells. Furthermore, a new class of potential caspase-1 inhibitors was investigated through the screening of a series of nonfluorogenic DHPs, utilizing our established caspase-1 fluorescent sensing system. Among the tested compounds, THD and FD showed caspase-1 inhibition with IC50 values of 2.8 ± 0.1 nM and 3.2 ± 0.1 µM, respectively. THD, which exhibited comparable potency to the well-known inhibitor VX-765 (3.68 nM), was selected for further investigation. Moreover, a competitive inhibition mechanism of THD at the enzyme's active site was supported by molecular docking and MD simulations. Western blot analysis of PMA-differentiated THP-1 cells further supported this observation by showing reduced cleaved IL-1β levels in the presence of THD. This inhibitory effect of THD on caspase-1 activity in a complex cell system was further confirmed by the concentration-dependent morphological changes in BMDMs.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 18","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149011713","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, Biological Evaluation, and Molecular Modeling of Novel Pyrimidine Scaffolds as Prospective Anticancer and Antimicrobial Agents 新型嘧啶支架的合成、生物学评价及分子模型研究。

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-09-17 DOI: 10.1002/cmdc.70502

Vishwa Thakor, Pratik Patel, Megha Patel, Bhavin Patel, Tarun Patel, Paresh Patel

{"title":"Synthesis, Biological Evaluation, and Molecular Modeling of Novel Pyrimidine Scaffolds as Prospective Anticancer and Antimicrobial Agents","authors":"Vishwa Thakor, Pratik Patel, Megha Patel, Bhavin Patel, Tarun Patel, Paresh Patel","doi":"10.1002/cmdc.70502","DOIUrl":"10.1002/cmdc.70502","url":null,"abstract":"A series of novel pyrimidine-based acetamide derivatives (5a–5j) containing various cyclic amine substituents were designed, synthesized, and structurally characterized to identify new lead compounds with dual antiproliferative and antimicrobial activities. The synthesized compounds were evaluated for antiproliferative activity against K562 human chronic myeloid leukemia, MCF-7 human breast adenocarcinoma, and HeLa human cervical carcinoma cell lines, while selectivity toward BJ fibroblasts was assessed. Antimicrobial activity was investigated against representative Gram-positive, Gram-negative, and fungal pathogens. Among the synthesized derivatives, compound 5h exhibited the highest antiproliferative activity with IC50 values of 6.39 ± 0.61, 10.34 ± 0.83, and 8.90 ± 0.71 μM against K562, MCF-7, and HeLa cells, respectively, while demonstrating comparatively lower cytotoxicity toward BJ cells. Compound 5h also displayed the most potent antibacterial activity against Escherichia coli (MBC = 25 μg/mL) and Pseudomonas aeruginosa (MBC = 50 μg/mL), together with promising antifungal activity. Structure–activity relationship analysis revealed that appropriately substituted aromatic cyclic amines significantly improved biological activity. Molecular docking against ABL1 kinase (PDB ID: 3PYY), together with DFT and ADME studies, supported the experimental findings. These results identify pyrimidine-based acetamide derivatives as promising multifunctional scaffolds for developing novel anticancer and antimicrobial agents.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 18","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987187","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

Peptide-Enabled Nanoplatforms for Malaria and Leishmaniasis: From Intracellular Targeting to Translational Diagnostic Perspectives 疟疾和利什曼病的肽激活纳米平台：从细胞内靶向到翻译诊断的观点。

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-09-16 DOI: 10.1002/cmdc.70493

Christian S. Carnero Canales, Ana Clara Lunardi Yagi, Túlio Custódio Reis, Jessica Ingrid Cazorla, Jade Rojas Villar, Marcia A. Graminha, Roxana Yesenia Pastrana Alta, Fernando Rogério Pavan

{"title":"Peptide-Enabled Nanoplatforms for Malaria and Leishmaniasis: From Intracellular Targeting to Translational Diagnostic Perspectives","authors":"Christian S. Carnero Canales, Ana Clara Lunardi Yagi, Túlio Custódio Reis, Jessica Ingrid Cazorla, Jade Rojas Villar, Marcia A. Graminha, Roxana Yesenia Pastrana Alta, Fernando Rogério Pavan","doi":"10.1002/cmdc.70493","DOIUrl":"10.1002/cmdc.70493","url":null,"abstract":"Malaria and leishmaniasis continue to impose a substantial health burden, while current therapeutic and diagnostic strategies remain limited by toxicity, prolonged regimens, drug resistance, and restricted field applicability. This review examines recent advances in peptide-enabled nanoplatforms for both diseases, with emphasis on intracellular targeting, drug delivery, and diagnostic innovation. Antimicrobial peptides, cell-penetrating peptides, peptoids, mimotopes, and peptide-functionalized nanocarriers have been explored to improve parasite targeting, intracellular delivery, pharmacokinetics, and antiparasitic efficacy. In parallel, peptide- and aptamer-based nanosensors have expanded the detection of clinically relevant biomarkers, including HRP2, pLDH, GP63, KMP-11, and kDNA, highlighting their potential for sensitive and modular diagnostics. Despite these advances, translation remains constrained by limited in vivo validation, insufficient pharmacokinetic standardization, incomplete toxicity profiling, poor batch reproducibility, protein corona-associated variability, and scarce validation under field-relevant conditions. Peptide-enabled nanoplatforms are therefore most likely to succeed when aligned with stage-specific parasite biology, realistic host cell-targeting requirements, and scalable implementation pathways in endemic settings.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 18","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.70493","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148981655","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

New 1,3-Oxazole and 1,2,4-Oxadiazole Derivatives as Novel Agents Against Human Rhinovirus and Cytomegalovirus 新的1,3-恶唑和1,2,4-恶二唑衍生物作为抗人鼻病毒和巨细胞病毒的新药物。

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-09-15 DOI: 10.1002/cmdc.70491

Yelyzaveta Yu. Rybina, Maryna V. Kachaeva, Agnieszka B. Olejniczak, Marta Denel-Bobrowska, Victor V. Zhirnov, Ivan V. Semenyuta, Stepan G. Pilyo

{"title":"New 1,3-Oxazole and 1,2,4-Oxadiazole Derivatives as Novel Agents Against Human Rhinovirus and Cytomegalovirus","authors":"Yelyzaveta Yu. Rybina, Maryna V. Kachaeva, Agnieszka B. Olejniczak, Marta Denel-Bobrowska, Victor V. Zhirnov, Ivan V. Semenyuta, Stepan G. Pilyo","doi":"10.1002/cmdc.70491","DOIUrl":"10.1002/cmdc.70491","url":null,"abstract":"A library of 16 new five-functionalized derivatives of 2-undecyl- and 1,2,4-oxadiazole-containing 2-aryl-4-cyano-1,3-oxazoles was synthesized using α-acylamino-β,β-dichloroacrylonitriles as key building blocks, enabling efficient formation of diverse 1,3-oxazole, oxadiazole–oxazole, and sulfonamide–oxazole systems. The antiviral potential was evaluated in vitro against rhinovirus 8 (HRV8), cytomegalovirus (HCMV), parainfluenza virus type 3 (HPIV-3), and zoonotic encephalomyocarditis virus (EMCV). Screening revealed distinct activity profiles: none of the compounds inhibited EMCV or HPIV-3, while several demonstrated pronounced efficacy against HRV8 and HCMV. In concentration-dependent assays, compounds 1, 7, 10, 13, and 14 exhibited potent anti-HCMV effects (IC50 = 0.42–4.67 µM). Compound 7 showed remarkable selectivity (SI = 465), outperforming ganciclovir (GCV, SI = 326). Against HRV8, compound 2 was the most active (IC50 = 1.67 µM, SI = 11), whereas compound 13 displayed weak activity (IC50 = 21.0 µM, SI = 1). All molecules met drug-likeness criteria with favorable ADMET-predicted pharmacokinetic parameters. Molecular docking suggested that derivatives 7, 10, 13, and 14 may target viral DNA polymerase, with binding energies from –8.8 to –9.7 kcal mol−1. These findings demonstrate that 1,3-oxazoles represent a promising chemotype for new antiviral candidates active against HCMV and HRV8.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 18","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975065","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

Corrigendum to “Rational Design of Ruthenium Complexes Containing 2,6-Bis(benzimidazolyl)pyridine Derivatives With Radiosensitization Activity by Enhancing p53 Activation” “合理设计含有2,6-双（苯并咪唑）吡啶衍生物的钌配合物，通过增强p53激活具有放射增敏活性”的勘误表。

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-09-15 DOI: 10.1002/cmdc.70492

Zhiqin Deng, Lianling Yu, Wenqiang Cao, Wenjie Zheng, Tianfeng Chen

引用次数: 0

Linker Optimization of cMYC RIBOTAC for Efficient cMYC Modulation 高效cMYC调制的cMYC RIBOTAC连接体优化

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-09-15 DOI: 10.1002/cmdc.70495

Sivakumar Komachankandy, Jinseo Heo, Yerin Kim, Wonpil Im, Yeongju Lee

引用次数: 0

Metal-Based Photosensitizers as Emerging Antibacterial Agents for Infected Wound Healing. 金属基光敏剂在感染伤口愈合中的应用

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-09-14 DOI: 10.1002/cmdc.70479

Arif Ali Mandal, Bhaskar Bhusan Das, Ishwar Singh, Samya Banerjee

{"title":"Metal-Based Photosensitizers as Emerging Antibacterial Agents for Infected Wound Healing.","authors":"Arif Ali Mandal, Bhaskar Bhusan Das, Ishwar Singh, Samya Banerjee","doi":"10.1002/cmdc.70479","DOIUrl":"10.1002/cmdc.70479","url":null,"abstract":"Wound infection has become a significant public health challenge worldwide. Inappropriate wound care and excessive use of antibiotics often compromise treatment outcomes, leading to the emergence of antimicrobial resistance. Hence, development of novel, more effective treatment strategies is essential to reduce infection-associated mortality and minimize treatment-related side effects. Recently, antibacterial photodynamic therapy (aPDT) has attracted considerable attention for the management of infected wounds. Several studies have investigated the application of aPDT for wound healing using in vivo animal models. aPDT effectively eliminates pathogenic bacteria while also promoting fibroblast proliferation and accelerating tissue regeneration and wound repair. To further improve aPDT efficiency, the development of advanced photosensitizers (PSs) has become a key research focus. Recently, metal-based PSs have attracted significant attention owing to their strong light absorption, long-lived excited states, and efficient generation of reactive oxygen species (ROS), which enhance light-triggered antimicrobial activity. Despite these promising properties, their application in the healing of infected wounds remains largely underexplored, with only a few reports to date. This highlights an important opportunity to further develop metal-based PSs as effective aPDT agents for wound treatment. Therefore, this perspective critically discusses recent advances and outlines future directions for developing more effective PDT-assisted wound-healing strategies.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 17","pages":"e70479"},"PeriodicalIF":3.5,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928591","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

Tearing Down Scientific Boundaries: Frontiers in Medicinal Chemistry 2026 打破科学界限：药物化学前沿2026

IF 3.5 4区医学

ChemMedChem Pub Date : 2026-09-13 DOI: 10.1002/cmdc.70490

Pascal Heitel, Philipp Barbie, Alessia Gambardella, Marta Pinto, Felix Pape, Anika Tarasewicz, Gerhard Hessler, Bernhard Wünsch, Matthias Schiedel, Christina Lamers

引用次数: 0