ChemMedChem最新文献_第3页

Discovery of Galactopyranose-1-carboxamides as a New Class of Small, Novel, Potent, Selective, and Orally Active Galectin-3 Inhibitors.

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-12 DOI: 10.1002/cmdc.202401012

Cornelia Zumbrunn, Luboš Remen, Christoph P Sager, Corinna Grisostomi, Christina Stamm, Daniela Krüsi, Sven Glutz, Gunther Schmidt, Oliver Nayler, Marc Iglarz, Aengus Mac Sweeney, Alain Chambovey, Manon Müller, Celia Mueller, Geoffroy Bourquin, Solange Meyer, Eva Hühn, Christophe Cattaneo, Magali Vercauteren, John Gatfield, Martin H Bolli

{"title":"Discovery of Galactopyranose-1-carboxamides as a New Class of Small, Novel, Potent, Selective, and Orally Active Galectin-3 Inhibitors.","authors":"Cornelia Zumbrunn, Luboš Remen, Christoph P Sager, Corinna Grisostomi, Christina Stamm, Daniela Krüsi, Sven Glutz, Gunther Schmidt, Oliver Nayler, Marc Iglarz, Aengus Mac Sweeney, Alain Chambovey, Manon Müller, Celia Mueller, Geoffroy Bourquin, Solange Meyer, Eva Hühn, Christophe Cattaneo, Magali Vercauteren, John Gatfield, Martin H Bolli","doi":"10.1002/cmdc.202401012","DOIUrl":"10.1002/cmdc.202401012","url":null,"abstract":"Galectin-3 (Gal-3), a β-galactoside-binding lectin, is implicated in diverse cellular functions ranging from immune response modulation to tissue homeostasis. Notably, increased Gal-3 expression has been linked to the progression of numerous diseases, including cancer, fibrosis, and cardiovascular disorders, underscoring its potential as a therapeutic target. Small molecule inhibitors have been discovered and are valuable tools to study such diseases. We report here the discovery of novel, galactose-based, small molecule inhibitors such as compound 12 which are orally bioavailable and show efficacy in a mouse model of acute liver injury and fibrosis (CCl4 model). The use of structure-based drug design (docking of a virtual library of amides based on acid 2) was key in the process towards potent, nanomolar inhibitors.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202401012"},"PeriodicalIF":3.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602989","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

Isoniazid-Dihydropyrimidinone Molecular Hybrids: Design, Synthesis, Antitubercular Activity, and Cytotoxicity Investigations with Computational Validation.

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-11 DOI: 10.1002/cmdc.202400949

Gobind Kumar, Pule Seboletswe, Sahil Mishra, Neha Manhas, Safiyah Ghumran, Nagaraju Kerru, Françoise Roquet-Banères, Maëlle Foubert, Laurent Kremer, Gaurav Bhargava, Parvesh Singh

{"title":"Isoniazid-Dihydropyrimidinone Molecular Hybrids: Design, Synthesis, Antitubercular Activity, and Cytotoxicity Investigations with Computational Validation.","authors":"Gobind Kumar, Pule Seboletswe, Sahil Mishra, Neha Manhas, Safiyah Ghumran, Nagaraju Kerru, Françoise Roquet-Banères, Maëlle Foubert, Laurent Kremer, Gaurav Bhargava, Parvesh Singh","doi":"10.1002/cmdc.202400949","DOIUrl":"10.1002/cmdc.202400949","url":null,"abstract":"A new series of isoniazid-dihydropyrimidinone molecular hybrids (8a-8n) were designed, synthesized and structurally characterized using different spectroscopic techniques viz., Fourier transform infrared spectroscopy, nuclear magnetic resonance (NMR), and high-resolution mass spectrometry followed by their antitubercular evaluation including their precursors (4a-4n), and a standard antitubercular drug (isoniazid; INH). The molecular hybrids particularly 8g (minimum inhibitory concentration (MIC) = 6.25 μg mL-1), 8h (MIC = 1.56 μg mL-1), 8k (MIC = 0.78 μg mL-1), 8l (MIC = 6.25 μg mL-1), and 8n (MIC = 0.39 μg mL-1) demonstrated the most potent inhibitory activity against wild-type M. tuberculosis mc26230, disclosing 8n as the most potent compound in the series. However, the potent compounds lost their activity against three INH-resistant M. tuberculosis strains mutated in katG. The more efficient compounds (8h, 8k, and 8n) were subsequently evaluated for their cytotoxicity against the THP-1 human monocytic cell line. Furthermore, the stability studies of the most potent compound carried out using 1H NMR, UV-visible, and liquid chromatography-mass spectrometry revealed their structural integrity. Finally, in silico molecular docking simulations were conducted to explore the binding orientations of the potent compounds in the active site of the target protein InhA while ADME/T (absorption, distribution, metabolism, excretion, and toxicity) and global reactivity parameters were explored to determine their drug-likeness and stability profiles, respectively.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e2400949"},"PeriodicalIF":3.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603007","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

Ergosterol and Lanosterol Derivatives: Synthesis and Possible Biomedical Applications.

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-09 DOI: 10.1002/cmdc.202400948

Joanna Stefaniak-Skorupa, Maria J Milewska

引用次数: 0

Methods for the Generation of Single-Payload Antibody-Drug Conjugates.

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-07 DOI: 10.1002/cmdc.202500132

Thomas Wharton, David R Spring

引用次数: 0

Front Cover: Carbon-13 Hyperpolarization of α-Ketocarboxylates with Parahydrogen in Reversible Exchange (ChemMedChem 5/2025)

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-06 DOI: 10.1002/cmdc.202580501

Stephen J. McBride, Keilian MacCulloch, Patrick TomHon, Austin Browning, Samantha Meisel, Mustapha Abdulmojeed, Boyd M. Goodson, Eduard Y. Chekmenev, Thomas Theis

引用次数: 0

Cover Feature: Current Context of Designing Phototheranostic Cyclometalated Iridium (III) Complexes to Open a New Avenue in Cancer Therapy (ChemMedChem 5/2025)

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-06 DOI: 10.1002/cmdc.202580502

Sreelekha U, Uttara Basu, Prof. Priyankar Paira

{"title":"Cover Feature: Current Context of Designing Phototheranostic Cyclometalated Iridium (III) Complexes to Open a New Avenue in Cancer Therapy (ChemMedChem 5/2025)","authors":"Sreelekha U, Uttara Basu, Prof. Priyankar Paira","doi":"10.1002/cmdc.202580502","DOIUrl":"https://doi.org/10.1002/cmdc.202580502","url":null,"abstract":"The cover art features an iridium complex with distinct cyclometalated ligands that enhance both bioimaging and therapeutic properties. The illustration also highlights the therapeutic function, where the iridium complex, upon light irradiation, induces apoptosis or cellular damage, representing its targeted cancer-fighting capabilities. The review article presents the current advancements and future potential of cyclometalated iridium (III) complexes as a phototheranostic agent. The finding demonstrates that cyclometalated iridium (III) complexes hold significant promise for both bioimaging and therapeutic purposes, showcasing potent anticancer activity that addresses the limitations of conventional cancer therapies by enabling more effective targeted delivery. More details can be found in article 10.1002/cmdc.202400649 by Priyankar Paira and co-workers.<figure>\u0000 <div><picture>\u0000 <source></source></picture>\u0000 </div>\u0000 </figure>\u0000 ","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 5","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202580502","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565056","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

Signaling Pathways and Promising Small-Molecule Therapeutic Agents for Ischemic Stroke.

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-03-02 DOI: 10.1002/cmdc.202400975

Debasis Das, Yimeng Wu, Jian Hong

{"title":"Signaling Pathways and Promising Small-Molecule Therapeutic Agents for Ischemic Stroke.","authors":"Debasis Das, Yimeng Wu, Jian Hong","doi":"10.1002/cmdc.202400975","DOIUrl":"10.1002/cmdc.202400975","url":null,"abstract":"Stroke is the second highest cause of death and leading cause of disability with high economic burden worldwide. The incidence of stroke is increasing faster and more prevalent for the global population over age 65. Ischemic stroke (IS) has a higher incidence than hemorrhagic stroke, accounting over 80 % of the total incidence of stroke. The rate of ischemic stroke is increasing in all age groups and both sexes. In present era, hypertension, high blood pressure and modern lifestyle are considered as the causes of the disease. The treatment options for stroke is still limited, mainly thrombolytic and thrombectomy therapy are available options. In the past decade, a number of therapeutic agents have been studied for the acute ischemic stroke to protect the brain from ischemic injury. Several study methods focus to improve neurons functions around the ischemic core and protect from the shock. Many signalling pathways including NF-kB, NrF, Nrf2-Keap1, PI3K/AKT, JAK/STAT signalling pathways are strongly associated for the indication. Controlling the signalling pathways by small molecules potentially improve the neuronal functions. In this article, we review the recent advancement of the drug discovery, controlling the signalling pathways by small molecules, and kinase inhibitors in ischemic stroke.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400975"},"PeriodicalIF":3.6,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536278","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

Quinoline ATP Synthase Inhibitors with Activity Against Multidrug Resistant Acinetobacter baumannii and Pseudomonas aeruginosa. 对耐多药鲍曼不动杆菌和铜绿假单胞菌具有活性的喹啉 ATP 合成酶抑制剂

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-02-27 DOI: 10.1002/cmdc.202400952

Katie T Ward, Alexander P L Williams, Angelina L Dennison, Lena Aamir, Darien L Allen, Britza Chavez-Arellano, Toni A Marchlewski, Mars L Zappia, Amanda L Wolfe, P Ryan Steed

{"title":"Quinoline ATP Synthase Inhibitors with Activity Against Multidrug Resistant Acinetobacter baumannii and Pseudomonas aeruginosa.","authors":"Katie T Ward, Alexander P L Williams, Angelina L Dennison, Lena Aamir, Darien L Allen, Britza Chavez-Arellano, Toni A Marchlewski, Mars L Zappia, Amanda L Wolfe, P Ryan Steed","doi":"10.1002/cmdc.202400952","DOIUrl":"10.1002/cmdc.202400952","url":null,"abstract":"The Gram-negative, pathogenic bacteria Acinetobacter baumannii (AB) and Pseudomonas aeruginosa (PA) have been identified as a particular threat due to rising multidrug resistance, and antibiotics with novel mechanisms of action are needed. Bacterial bioenergetics is a promising but underdeveloped drug target since the complexes of oxidative phosphorylation are critical to cell survival in these organisms. Building from our previous work using quinoline derivatives to inhibit the ATP synthase of PA, we report a new set of 14 quinoline derivatives that demonstrates potent inhibition of the AB ATP synthase, with the best inhibitor having an IC50 of 230 ng/mL in vitro, expands the quinoline structure-activity relationship against the PA enzyme, and establishes molecular strategies for achieving selectivity between PA and AB. Furthermore, several compounds demonstrated potent antibacterial activity against multidrug resistant strains of AB and PA indicating ATP synthase as a promising new area for broad spectrum antibiotic development in AB.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400952"},"PeriodicalIF":3.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522158","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 Safe COX-2 Inhibitors: Achieving Reduced Colitis Side Effects through Balanced COX Inhibition.

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-02-27 DOI: 10.1002/cmdc.202500096

Xinlin Zhu, Qin Li, Junhui Wu, Zhiran Ju

引用次数: 0

A Career doing STUFF.

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-02-26 DOI: 10.1002/cmdc.202401017

Michael M Hann

引用次数: 0