IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-23 DOI: 10.1002/cmdc.202400971

Marta Kučerová-Chlupáčová

引用次数: 0

Aminocholestane and Aminoandrostane Inhibitors of the SH2 Domain-Containing Inositol 5'-Phosphatase (SHIP).

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-22 DOI: 10.1002/cmdc.202400597

Angela M Pacherille, Dennis R Viernes, Chiara Pedicone, Sandra Fernandes, Otto M Dungan, Shawn Dormann, Daniel R Wallach, Raki Sudan, Robbie Brooks, Christopher M Russo, Kyle T Howard, Michael S Cosgrove, William G Kerr, John D Chisholm

引用次数: 0

Addressing Data Point Homogeneity and Annotation Challenges to Enhance Data-Driven Approaches: The S. aureus NorA Efflux Pump Case Study.

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-22 DOI: 10.1002/cmdc.202400927

Andrea Astolfi, Giada Cernicchi, Erika Primavera, Marco Rocchi, Giuseppe Manfroni, Stefano Sabatini, Maria Letizia Barreca

引用次数: 0

Binding-site switch of Protein Kinase CK2 inhibitors. 蛋白激酶CK2抑制剂的结合位点转换。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-21 DOI: 10.1002/cmdc.202400868

Isabelle Krimm, Dylan Grenier, Muriel Gelin, Yinshan Yang Cbs Cnrs Fr, Angélique Mularoni, Jean-François Guichou, Jean-Guy Delcros

{"title":"Binding-site switch of Protein Kinase CK2 inhibitors.","authors":"Isabelle Krimm, Dylan Grenier, Muriel Gelin, Yinshan Yang Cbs Cnrs Fr, Angélique Mularoni, Jean-François Guichou, Jean-Guy Delcros","doi":"10.1002/cmdc.202400868","DOIUrl":"https://doi.org/10.1002/cmdc.202400868","url":null,"abstract":"The serine/threonine protein kinase CK2, a tetramer composed of a regulatory dimer (CK2β2) bound to two catalytic subunits CK2α, is a well-established therapeutic target for various pathologies, including cancer and viral infections. Several types of CK2 inhibitors have been developed, including inhibitors that bind to the catalytic ATP-site, bivalent inhibitors that occupy both the CK2α ATP-site and the αD pocket, and inhibitors that target the CK2α/CK2β interface. Interestingly, the bivalent inhibitor AB668 shares a similar chemical structure with the interface inhibitor CCH507. In this study, we designed analogs of CCH507 using structure-based and fragment-based approaches. The ability of these analogs to bind the CK2α/CK2β interface was evaluated using biolayer interferometry and fluorescence anisotropy-based assays. Their potency to inhibit CK2 kinase activity was determined using the bioluminescent ADP-Glo assay. These experiments allowed us to investigate which chemical modifications prevent the binding of the compounds at the CK2α/CK2β interface. Seven out of sixteen compounds conserved the ability to bind at the protein-protein interface, among which three compounds exhibited better interface inhibition compared to CCH507.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400868"},"PeriodicalIF":3.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996881","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

Unveiling Gelation and Antimicrobial Potentials of α-Acyloxy Carboxamides: Findings from Experimental and Theoretical Approach. 揭示α-酰基羧胺的凝胶化和抗菌潜力：实验和理论方法的发现。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-21 DOI: 10.1002/cmdc.202400774

Sharol Sebastian, Manjeet Kumar, Feroze Hussain, Sanju Rathore, Yajat Rohila, Meenakshi Goyat, Shaurya Prakash, Antresh Kumar, Priya Bhardwaj, Mulaka Maruthi, Azaj Ansari, Manoj Kumar Gupta

{"title":"Unveiling Gelation and Antimicrobial Potentials of α-Acyloxy Carboxamides: Findings from Experimental and Theoretical Approach.","authors":"Sharol Sebastian, Manjeet Kumar, Feroze Hussain, Sanju Rathore, Yajat Rohila, Meenakshi Goyat, Shaurya Prakash, Antresh Kumar, Priya Bhardwaj, Mulaka Maruthi, Azaj Ansari, Manoj Kumar Gupta","doi":"10.1002/cmdc.202400774","DOIUrl":"https://doi.org/10.1002/cmdc.202400774","url":null,"abstract":"Multicomponent reactions have long been recognized as some of the most versatile tools in organic chemistry, with extensive applications in biomedical science and the pharmaceutical industry. In this study, we explored the potential of the Passerini reaction by designing and synthesizing new low molecular mass gelators that can serve as novel formulations for prolonged anesthesia. These gelators address critical issues like poor solubility, low bioavailability, and short plasma half-life, all of which hinder therapeutic efficacy. To further understand the gelation mechanism, we performed density functional theory (DFT) calculation for confirming the presence of non-covalent interactions during gel formation. Additionally, we evaluated the antimicrobial properties of the synthesized compounds, aiming to counter the rise of infectious diseases. These innovative antimicrobial agents could offer solutions to the growing problem of antibiotic resistance, which renders many existing therapies ineffective. Overall, this study aims to develop advanced formulations and antimicrobial agents through the Passerini reaction, providing new strategies for treating infections, minimizing side effects, and combating antibiotic resistance.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400774"},"PeriodicalIF":3.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996925","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

Effects of Cholesterol on the Breast Cancer Resistance Protein: Studies through the Synthesis and Biological Evaluation of Chemical Tools. 胆固醇对乳腺癌抵抗蛋白的影响：化学工具的合成及生物学评价研究

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-21 DOI: 10.1002/cmdc.202400712

Ahcène Boumendjel, Ingrid Fatima Zattoni, Bruna Estelita Rugisnk, Isadora da Silva Zanzarini, Alan Guilherme Gonçalves, Vivian Rotuno Moure, Glaucio Valdameri

{"title":"Effects of Cholesterol on the Breast Cancer Resistance Protein: Studies through the Synthesis and Biological Evaluation of Chemical Tools.","authors":"Ahcène Boumendjel, Ingrid Fatima Zattoni, Bruna Estelita Rugisnk, Isadora da Silva Zanzarini, Alan Guilherme Gonçalves, Vivian Rotuno Moure, Glaucio Valdameri","doi":"10.1002/cmdc.202400712","DOIUrl":"https://doi.org/10.1002/cmdc.202400712","url":null,"abstract":"The breast cancer resistance protein (BCRP/ABCG2) plays a major role in the multidrug resistance of cancers toward chemotherapeutic treatments. It was demonstrated that cholesterol regulates the ABCG2 activity, suggesting that lower levels of membrane cholesterol decrease the ABCG2 activity in mammalian cells. However, the precise mechanism remains unclear. To better understand the role of cholesterol in the ABCG2 activity, we studied the ABCG2-mediated efflux of different substrates in the presence of different concentrations of cholesterol. Moreover, we synthetized derivatives of cholesterol linked either to known ABCG2 inhibitors or fluorescents probes. A chalcone-cholesterol was synthetized to investigate the influence of cholesterol on ABCG2 inhibition, and a BODIPY-cholesterol was developed to track cholesterol trafficking on mammalian cells and investigate the behavior of cholesterol as an ABCG2 substrate. The obtained results with three different substrates of ABCG2 showed that cholesterol did not affect the intracellular amount of substrates nor the transport activity.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400712"},"PeriodicalIF":3.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996888","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

β-Glucuronidase-Responsive Albumin-Binding Prodrug of Colchicine-Site Binders for Selective cancer Therapy. β-葡萄糖醛酸酶反应性白蛋白结合前药的秋水仙碱位点结合剂选择性癌症治疗。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-21 DOI: 10.1002/cmdc.202400969

Alexandra Bordes, Isabelle Opalinski, Fabien Thoreau, Olivier Provot, Mouad Alami, Abdallah Hamze, Sébastien Papot

引用次数: 0

Diversity-oriented synthesis and antibiofilm evaluation of furan-2-carboxamides. 呋喃-2-羧酰胺的合成及抗菌膜评价。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-20 DOI: 10.1002/cmdc.202400879

Eduardo Hernández-Vázquez, Ana C Muñoz-Estrada, Cesar E Tovar-Roman, Carlos D García-Mejía, Rodolfo García-Contreras

引用次数: 0

Towards Improved Peptidic α-Ketoamide Inhibitors of the Plasmodial Subtilisin-Like SUB1: Exploration of N-Terminal Extensions and Cyclic Constraints. 改良的疟原虫样枯草杆菌SUB1肽α-酮酰胺抑制剂：n端延伸和循环约束的探索

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-20 DOI: 10.1002/cmdc.202400924

Anna K Puszko, Fernando A Batista, Abdelaziz Ejjoummany, Anthony Bouillon, Manon Maurel, Pauline Adler, Alice Legru, Mariano Martinez, Laura Ortega Varga, Margot Hadjadj, Pedro M Alzari, Arnaud Blondel, Ahmed Haouz, Jean-Christophe Barale, Jean-François Hernandez

{"title":"Towards Improved Peptidic α-Ketoamide Inhibitors of the Plasmodial Subtilisin-Like SUB1: Exploration of N-Terminal Extensions and Cyclic Constraints.","authors":"Anna K Puszko, Fernando A Batista, Abdelaziz Ejjoummany, Anthony Bouillon, Manon Maurel, Pauline Adler, Alice Legru, Mariano Martinez, Laura Ortega Varga, Margot Hadjadj, Pedro M Alzari, Arnaud Blondel, Ahmed Haouz, Jean-Christophe Barale, Jean-François Hernandez","doi":"10.1002/cmdc.202400924","DOIUrl":"https://doi.org/10.1002/cmdc.202400924","url":null,"abstract":"After more than 15 years of decline, the Malaria epidemy has increased again since 2017, reinforcing the need to identify drug candidates active on new targets involved in at least two biological stages of the Plasmodium life cycle. The SUB1 protease, which is essential for parasite egress in both hepatic and blood stages, would meet these criteria. We previously reported the structure-activity relationship analysis of α-ketoamide-containing inhibitors encompassing positions P4-P2'. Despite compounds with high inhibitory potencies were identified, their antiparasitic activity remained limited, probably due to insufficient cell permeability. Here, we present our efforts to improve it through the N-terminal introduction of basic or hydrophobic moieties and/or cyclization. Compared to our previous reference compounds 1/2 (Ac-Ile/Cpg-Thr-Ala-AlaCO-Asp-Glu(Oall)-NH2), we identified analogues with improved Pf-/PvSUB1 inhibition (IC50 values in the 10-20 nM range) and parasite growth inhibition (up to 98% at 100 μM). The increase in potency was mainly observed when increasing the overall hydrophobicity of the compounds. Conjugation to the cell penetrating peptide octa-arginine was also favorable. Finally, the crystal structure of PvSUB1 in complex with compound 15 has been determined at 1.6 Å resolution. Compared to compound 1, this structure extended to the P5 residue and revealed two additional hydrogen bonds.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400924"},"PeriodicalIF":3.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996911","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

Pillar[n]arene-Based Supramolecular Nanodrug Delivery Systems for Cancer Therapy. 基于芳烃的超分子纳米药物递送系统在肿瘤治疗中的应用。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-20 DOI: 10.1002/cmdc.202400822

Shubin Wei, Xinyi Cui, Tingting Li, Xin Ma, Luzhi Liu

引用次数: 0

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