ChemMedChem最新文献_第9页

Direct-to-Biology: Streamlining the Path From Chemistry to Biology in Drug Discovery 直接到生物学：简化药物发现从化学到生物学的路径。

IF 3.4 4区医学

ChemMedChem Pub Date : 2026-02-20 DOI: 10.1002/cmdc.202501080

Ariane F. Hübner, Fabian Barthels

引用次数: 0

Targeting Inflammatory and Oncogenic Pathways: Cyclooxygenase-2, Epidermal Growth Factor Receptor, and p38 Mitogen-Activated Protein Kinase Inhibition by Pyrazolone Derivatives 针对炎症和致癌途径：环氧化酶-2、表皮生长因子受体和p38丝裂原活化蛋白激酶抑制吡唑啉酮衍生物。

IF 3.4 4区医学

ChemMedChem Pub Date : 2026-02-20 DOI: 10.1002/cmdc.202500778

Sevde Nur Biltekin Kaleli, Evren Önay Uçar, Zafer Şahin, Barkın Berk, Şeref Demirayak

{"title":"Targeting Inflammatory and Oncogenic Pathways: Cyclooxygenase-2, Epidermal Growth Factor Receptor, and p38 Mitogen-Activated Protein Kinase Inhibition by Pyrazolone Derivatives","authors":"Sevde Nur Biltekin Kaleli, Evren Önay Uçar, Zafer Şahin, Barkın Berk, Şeref Demirayak","doi":"10.1002/cmdc.202500778","DOIUrl":"10.1002/cmdc.202500778","url":null,"abstract":"Acute and chronic inflammation are known to contribute to the pathogenesis of various diseases, including cardiovascular disorders, Parkinson's, Alzheimer's, diabetes, and cancer. Classical nonsteroidal anti-inflammatory drugs reduce inflammation primarily by suppressing the cyclooxygenase (COX) pathway. COX enzymes facilitate the conversion of membrane phospholipids into prostaglandins and play functional roles in several metabolic processes, including analgesia, anti-inflammation, apoptosis, angiogenesis, and drug resistance. Moreover, they are also implicated in cancer development, invasion, metastasis, and the differentiation. In this study, eight pyrazolone derivative compounds with potential anti-inflammatory properties were synthesized. Their structures were successfully characterized using 1H nuclear magnetic resonance (NMR), 13C NMR, infrared spectroscopy (IR), and high-resolution mass spectrometry (HRMS) spectroscopy. Their inhibitory activities againt COX-1, COX-2, and 5-lipoxygenase were evaluated to determine their anti-inflammatory potential. Epidermal growth factor receptor inhibition assays were performed for the active compounds 7 and 8, while compound 7, the most potent molecule, was further assessed for p38 mitogen-activated protein kinase inhibition. Several compounds exhibited selective cytotoxicity toward cancer cell lines. Notably, compounds 7 and 8 showed no inhibitory activity against COX-1 yet demonstrated considerable selectivity toward COX-2. Interestingly, some derivatives displaying selective cytotoxic effects were not among the most potent COX-2 inhibitors. Overall, the findings indicate that the synthesized pyrazolone derivatives represent promising lead candidates for the development of anti-inflammatory and anticancer agents.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224764","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

Therapeutic Exosomes for Rare Cancers: Advances and Clinical Translation 罕见癌症的治疗性外泌体：进展和临床翻译

IF 3.4 4区医学

ChemMedChem Pub Date : 2026-02-19 DOI: 10.1002/cmdc.202500653

Kavitha Unnikrishnan, Abhay Mahesh, Ram Mohan Ram Kumar

{"title":"Therapeutic Exosomes for Rare Cancers: Advances and Clinical Translation","authors":"Kavitha Unnikrishnan, Abhay Mahesh, Ram Mohan Ram Kumar","doi":"10.1002/cmdc.202500653","DOIUrl":"https://doi.org/10.1002/cmdc.202500653","url":null,"abstract":"Rare cancers collectively account for a proportion of cancer-related morbidity and mortality, and patients face significant challenges, including delayed diagnosis, lack of targeted therapies, and poor clinical outcomes. Exosome-based therapies have emerged as promising tools to address these unmet needs. Exosomes, naturally secreted extracellular vesicles, are increasingly engineered as nanocarriers for the targeted delivery of chemotherapeutics, nucleic acids, and immune modulators. Their ability to modulate the tumor microenvironment, influence immune responses, and overcome drug resistance makes them especially attractive. In rare cancers, preliminary studies have demonstrated the utility of exosomes in improving tumor specificity, enhancing payload stability, and reducing systemic toxicity. Moreover, exosomes derived from tumor or immune cells can influence immune evasion, angiogenesis, and stromal remodeling, key processes in cancer progression. Despite this potential, the clinical application of exosome-based therapies in rare cancers remains underexplored. This review critically evaluates the limited but emerging body of evidence supporting exosome-based interventions in rare malignancies. By highlighting their therapeutic promise, we aim to understand exosome-driven strategies as personalized, effective, and accessible solutions for patients with rare cancers.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224430","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

Cytotoxicity and Antimicrobial Activity of GaMF1 Analogs GaMF1类似物的细胞毒性和抗菌活性。

IF 3.4 4区医学

ChemMedChem Pub Date : 2026-02-19 DOI: 10.1002/cmdc.202500951

Jan Chasák, Petr Vyvlečka, Ivan Nemec, An Matheeussen, Natascha Van Pelt, Paul Cos, Guy Caljon, Vladimír Kryštof, Lucie Brulíková

{"title":"Cytotoxicity and Antimicrobial Activity of GaMF1 Analogs","authors":"Jan Chasák, Petr Vyvlečka, Ivan Nemec, An Matheeussen, Natascha Van Pelt, Paul Cos, Guy Caljon, Vladimír Kryštof, Lucie Brulíková","doi":"10.1002/cmdc.202500951","DOIUrl":"10.1002/cmdc.202500951","url":null,"abstract":"Recent studies have identified the mycobacterial adenosine triphosphate synthase inhibitor GaMF1 and its structural analogs as compounds with noteworthy antituberculosis activity. Despite these promising results, a significant limitation remains their cytotoxicity against human cells, which, in its current state, overshadows the therapeutic potential. Therefore, addressing this off-target toxicity is essential for the further development of these compounds as viable drug candidates. In this study, we systematically explored structural modifications of the original GaMF1 scaffold with the primary aim of reducing its inherent cytotoxicity. Individual regions of the parent structure were progressively replaced, enabling the identification of substituents that effectively attenuate cytotoxic effects. Importantly, these structural refinements also led to the emergence of pronounced antiparasitic activity, particularly against trypanosomal species such as Trypanosoma cruzi, Trypanosoma brucei brucei, and Trypanosoma brucei rhodesiense. These findings suggest that the biological potential of this compound class extends beyond what has previously been described. Furthermore, we evaluated the cytotoxicity of selected derivatives against a panel of tumor cell lines, where some compounds showed encouraging antiproliferative effects.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202500951","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224771","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

Exploring the Anticancer Properties and Mode of Action of Copper(II)-Furan Acylhydrazone on Human Triple Negative Breast Cancer Cells 铜(II)-呋喃酰基腙对人三阴性乳腺癌细胞的抗癌特性及作用方式探讨

IF 3.4 4区医学

ChemMedChem Pub Date : 2026-02-18 DOI: 10.1002/cmdc.202500836

Lucía Santa Maria de la Parra, Valeria R. Martínez, Nazia Nayeem, Maria Contel, Ignacio E. León

{"title":"Exploring the Anticancer Properties and Mode of Action of Copper(II)-Furan Acylhydrazone on Human Triple Negative Breast Cancer Cells","authors":"Lucía Santa Maria de la Parra, Valeria R. Martínez, Nazia Nayeem, Maria Contel, Ignacio E. León","doi":"10.1002/cmdc.202500836","DOIUrl":"https://doi.org/10.1002/cmdc.202500836","url":null,"abstract":"Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic treatments. This study evaluates the anticancer activity and mode of action of the copper(II) complex [Cu(HL1)(NO3)H2O]·H2O (CuHL1), derived from (E)-N’-(2-hydroxy-3-methoxybenzylidene)furan-2-carbohydrazide (H2L1), against a panel of TNBC cell lines (MDA-MB-231, MDA-MB-468, MDA-MB-157, HCC1806). CuHL1 exhibits potent cytotoxicity in the low micromolar range (IC50 ≈ 2 µM), surpassing cisplatin by up to 81-fold. In MDA-MB-231 cells, CuHL1 inhibits colony formation and induced reactive oxygen species (ROS) generation in a concentration-dependent manner. Moreover, CuHL1 triggers apoptosis as evidenced by Annexin V/PI staining and the modulation of Bax, Bcl-2, caspase-3, and cleaved caspase-3 protein levels. Label-free quantitative proteomics reveal 34 differentially expressed proteins, implicating pathways related to heat shock response, protein folding, lipid metabolism, and cell migration. Notably, CuHL1 downregulates BCAR3, AJUBA, MPZL1, TP53, FASN, and HMGCS1, suggesting inhibition of prometastatic and lipid biosynthetic processes. Functional assays confirm reduced migratory capacity in MDA-MB-231 cells. These findings position CuHL1 as a promising candidate for TNBC therapy, meriting further in vivo evaluation.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146217571","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

Exploration of Antiplasmodium Chemical Space Identifies New Inhibitors of β-Hematin Formation from Areas of Enrichment 抗疟原虫化学空间的探索从富集区发现β-血红素形成的新抑制剂。

IF 3.4 4区医学

ChemMedChem Pub Date : 2026-02-16 DOI: 10.1002/cmdc.202500752

Jessica L. Thibaud, Dirkie C. Myburgh, Rebecca D. Sandlin, Kim Y. Fong, Larnelle F. Garnie, Kathryn J. Wicht, David Kuter, David W. Wright, Timothy J. Egan, Katherine A. de Villiers

{"title":"Exploration of Antiplasmodium Chemical Space Identifies New Inhibitors of β-Hematin Formation from Areas of Enrichment","authors":"Jessica L. Thibaud, Dirkie C. Myburgh, Rebecca D. Sandlin, Kim Y. Fong, Larnelle F. Garnie, Kathryn J. Wicht, David Kuter, David W. Wright, Timothy J. Egan, Katherine A. de Villiers","doi":"10.1002/cmdc.202500752","DOIUrl":"10.1002/cmdc.202500752","url":null,"abstract":"The Tres Cantos Antimalarial Set (TCAMS) library is a valuable resource for identifying hits for the antimalarial pipeline. We used principal component analysis (PCA) to explore this tranche of chemical space. Applying a set of 17 two-dimensional (2D) molecular descriptors, the chemical space was mapped in 2D PC space. Thereafter, the locations of known inhibitors and noninhibitors of synthetic hemozoin (β-hematin) formation, a well-established drug target during the asexual blood stage of the Plasmodium falciparum parasite life cycle, were superimposed onto the 2D map and counted. Within the +PC1, −PC2 quadrant, an area of enrichment emerged that could be used to predict the activity of test compounds. A subset of 861 TCAMS compounds (45 inhibitors and 816 noninhibitors) yielded a 27% hit rate when filtered using the enrichment map. Thereafter, 81 diverse compounds with predicted activity were purchased and 20 (25%) were active. B37, which contains a pyrido carbazole scaffold, demonstrated potent β-hematin formation inhibitory activity (IC50 = 6.4 ± 0.19 μM) as well as noteworthy activity against the chloroquine-sensitive NF54 strain (IC50 = 0.32 ± 0.03 μM). The PCA enrichment map for β-hematin inhibition is a useful tool for rapid identification of potential hit compounds and may be extended in the future to other antimalarial targets.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12908436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146199532","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

Small Molecule Kinase Inhibitors with In Vitro β-Hematin Formation and Plasmodium falciparum Protein Kinase G Inhibitory Activity Identified Using Machine Learning 利用机器学习鉴定具有体外β-血红蛋白形成和恶性疟原虫蛋白激酶G抑制活性的小分子激酶抑制剂。

IF 3.4 4区医学

ChemMedChem Pub Date : 2026-02-15 DOI: 10.1002/cmdc.202500756

Jessica L. Thibaud, Nicolaas Salomane, Sarah Harries, Kathryn J. Wicht, Lauren B. Coulson, David Kuter, Kelly Chibale, Katherine A. de Villiers

引用次数: 0

Modeling of Paclitaxel Release From Magnetic Niosomes-Loaded Polycaprolactone/Chitosan Nanofiber Matrix Underan Alternating Magnetic Field 交变磁场作用下负载磁性纳米体的聚己内酯/壳聚糖纳米纤维基质紫杉醇释放模拟

IF 3.4 4区医学

ChemMedChem Pub Date : 2026-02-15 DOI: 10.1002/cmdc.202500685

Saeideh Masoumi Godgaz, Azadeh Asefnejad, S. Hajir Bahrami

{"title":"Modeling of Paclitaxel Release From Magnetic Niosomes-Loaded Polycaprolactone/Chitosan Nanofiber Matrix Underan Alternating Magnetic Field","authors":"Saeideh Masoumi Godgaz, Azadeh Asefnejad, S. Hajir Bahrami","doi":"10.1002/cmdc.202500685","DOIUrl":"10.1002/cmdc.202500685","url":null,"abstract":"In this study, a targeted and stimulus-responsive drug delivery system was designed and modeled for enhanced cancer therapy. Paclitaxel (PTX) release was investigated from trastuzumab-decorated SPION-loaded niosomes (TTSNs) integrated within polycaprolactone/chitosan electrospun fibers at varying TTSN concentrations (0%, 1%, 2.5%, and 5%) under both conventional and alternating magnetic field (AMF) conditions. The system was characterized using DLS, zeta potential, Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, EDX, and swelling analyses, while MTT assays assessed cytocompatibility. The TTSNs exhibited a spherical morphology with a mean size of 221 nm and a zeta potential of −14.7 mV. The resulting nanofibrous mats displayed smooth, uniform fibers with an average diameter of 200 nm. Incorporation of TTSNs did not alter fiber morphology but increased the swelling capacity. Drug release studies revealed that exposure to AMF significantly enhanced PTX release, particularly in mats containing 5% TTSNs, indicating a clear magneto-responsive behavior. Korsmeyer–Peppas modeling provided the best fit for PTX release profiles both with and without AMF. The release mechanism and model fitting varied with TTSN concentration, emphasizing the importance of optimizing nanoparticle content for specific therapeutic applications.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146199522","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

Positively Charged Polymers Based on Cyclodextrins for Trametinib and Selumetinib Delivery in Glioblastoma Cancer 基于环糊精的带正电荷聚合物在胶质母细胞瘤肿瘤中递送曲美替尼和塞鲁美替尼。

IF 3.4 4区医学

ChemMedChem Pub Date : 2026-02-15 DOI: 10.1002/cmdc.202501004

Noemi Bognanni, Maria Teresa Gentile, Antonia Feola, Valentina Giglio, Martina Dragone, Carla Isernia, Graziella Vecchio

{"title":"Positively Charged Polymers Based on Cyclodextrins for Trametinib and Selumetinib Delivery in Glioblastoma Cancer","authors":"Noemi Bognanni, Maria Teresa Gentile, Antonia Feola, Valentina Giglio, Martina Dragone, Carla Isernia, Graziella Vecchio","doi":"10.1002/cmdc.202501004","DOIUrl":"10.1002/cmdc.202501004","url":null,"abstract":"Glioblastoma (GB) is the most common and aggressive malignant brain tumor, with a median survival of only 12–15 months despite current treatments with surgery, radiotherapy, and temozolomide (TMZ). Although TMZ induces cytotoxic DNA methylation in tumor cells, its efficacy is often limited by resistance mechanisms. To overcome these limitations, alternative therapeutic strategies—such as targeting the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway with MEK inhibitors like trametinib and selumetinib—are being explored. However, their clinical success is currently hindered by inadequate delivery across the blood–brain barrier and dose-limiting toxicity. Nanoparticles, particularly positively charged systems, offer enhanced cellular uptake and therapeutic performance due to their strong interactions with negatively charged cell membranes. Cyclodextrin (CyD)-based polymers are promising systems owing to their low toxicity and ability to form inclusion complexes with drugs. In this work, we investigate two cationic CyD polymers as potential nanocarriers for GB therapy based on trametinib and selumetinib. Their multivalent architecture and positive charge can facilitate both the encapsulation of drugs and membrane interactions. These systems present promising candidates for enhancing the efficacy of GB treatment.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12906940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146199510","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

Biologically Active Natural δ-Lactones in Medicinal Chemistry: Structures, Bioactivities, and Synthesis 药物化学中具有生物活性的天然δ-内酯：结构、生物活性和合成

IF 3.4 4区医学

ChemMedChem Pub Date : 2026-02-12 DOI: 10.1002/cmdc.202500773

Dan-Bi Sung, Jong Seok Lee

{"title":"Biologically Active Natural δ-Lactones in Medicinal Chemistry: Structures, Bioactivities, and Synthesis","authors":"Dan-Bi Sung, Jong Seok Lee","doi":"10.1002/cmdc.202500773","DOIUrl":"https://doi.org/10.1002/cmdc.202500773","url":null,"abstract":"δ-Lactones are structurally diverse natural products broadly distributed across plants, fungi, microbes, and marine organisms. Their six-membered cyclic ester scaffold, often embedded in polyketide, terpenoid, fatty acid-derived, or hybrid frameworks, underpins wide-ranging pharmacological activities, including cytotoxic, antimicrobial, antiparasitic, and anti-inflammatory effects as well as modulation of enzymes and signaling pathways. Clinically relevant examples such as lovastatin, the first FDA-approved statin, and artemisinin, a cornerstone antimalarial, highlight the therapeutic value of δ-lactone motifs. In contrast, fostriecin and leptomycin B, though unsuccessful in the clinic, inspired analog development and validated new biological targets. Recent advances in synthesis—including ring-closing metathesis, CH lactonization, asymmetric annulations, and biomimetic approaches—have streamlined access to complex δ-lactones, enabling stereocontrolled synthesis and structure–activity relationship studies. This review provides a comprehensive overview of bioactive natural δ-lactones, organized by biosynthetic origin, and emphasizes their structural diversity, biological functions, and synthetic accessibility.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"21 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146176251","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