ChemMedChem最新文献_第4页

Bushy-Tailed Multicationic Quaternary Phosphonium Compounds: Potent Amphiphilic Disinfectants with Promising Therapeutic Indices. 丛生尾多重季鏻化合物：具有良好治疗指标的强效两性消毒剂。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-10-24 DOI: 10.1002/cmdc.202400546

Diana Rachii, Elise L Bezold, William M Wuest, Kevin P C Minbiole

{"title":"Bushy-Tailed Multicationic Quaternary Phosphonium Compounds: Potent Amphiphilic Disinfectants with Promising Therapeutic Indices.","authors":"Diana Rachii, Elise L Bezold, William M Wuest, Kevin P C Minbiole","doi":"10.1002/cmdc.202400546","DOIUrl":"10.1002/cmdc.202400546","url":null,"abstract":"Quaternary ammonium compounds (QACs) have been essential for protecting human health for almost a century, functioning as surface disinfectants and sanitizers. With bacterial resistance increasing against commercially available QACs, the development of novel antimicrobials with divergent architectures is essential for effective infection prevention and control. Toward this end, our group has expanded beyond traditional ammonium scaffolds and explored the development of quaternary phosphonium compounds (QPCs). Herein, we report the synthesis and biological investigation of a series of 20 novel multicationic QPCs, bearing multiple short alkyl or aryl chains, also referred to as \"bushy-tailed\" multiQPCs; these structures were hypothesized to have strong bioactivity while displaying low mammalian toxicity. Select bushy-tailed QPC derivatives with trishexylphosphonium groups displayed single-digit or sub-micromolar activity against all seven bacteria tested, and MIC values of 2- to 8-fold better than their bushy-tailed QAC counterparts. Importantly, therapeutic indices of these bushy-tailed QPCs were favorable in many cases, and were ≥4 against the entire bacterial panel for pX-P6*,P6* and 1,8-P6*,P6*, superior to more traditional architectures. This work highlights the promise of a novel set of multicationic phosphonium compounds as novel disinfectants with potent bioactivities and low toxicity.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400546"},"PeriodicalIF":3.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491518","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

Advanced Hydrogels: Enhancing Tissue Bioengineering with RGD Peptides and Carbon Nanomaterials. 高级水凝胶：利用 RGD 肽和碳纳米材料加强组织生物工程。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-10-24 DOI: 10.1002/cmdc.202400587

Josué M Galindo, Sonia Merino, M Antonia Herrero

{"title":"Advanced Hydrogels: Enhancing Tissue Bioengineering with RGD Peptides and Carbon Nanomaterials.","authors":"Josué M Galindo, Sonia Merino, M Antonia Herrero","doi":"10.1002/cmdc.202400587","DOIUrl":"10.1002/cmdc.202400587","url":null,"abstract":"The advancement of tissue engineering (TE) is driven by the development of scaffolds that mimic the mechanical, spatial, and biological environment of the extracellular matrix (ECM), crucial for regulating cell behavior and tissue repair. Hydrogels, 3D networks of polymer chains, are particularly suited for TE due to their high biocompatibility, ability to mimic tissue water content, facilitate cell migration, sustain growth factor release, and offer controllable physical properties. However, hydrogels mimicking the ECM often face challenges related to cell adhesion due to the absence of specific receptors. This issue can be addressed by incorporating ECM components into the polymer matrix, such as the peptide sequence arginine-glycine-aspartic acid (RGD), known for its role in cell adhesion. Additionally, carbon nanomaterials (CNMs) offer unique physicochemical properties that can improve scaffold-cell interactions. Despite the potential benefits, there are limited reports on their combination. RGD-CNM hydrogels enable a more accurate emulation of the natural cellular environment, enhancing tissue engineering applications. This hybrid approach may promote robust cell adhesion along with exceptional mechanical and electrical properties. This review outlines the potential benefits of these hybrid scaffolds and their synergistic potential, aiming to inspire new research directions in this innovative field.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400587"},"PeriodicalIF":3.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491517","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

Sensing and Imaging Agents for Cyclooxygenase Enzyme. 环氧化酶的传感和成像剂。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-10-23 DOI: 10.1002/cmdc.202400636

Subba Rao Cheekatla, Dhiraj P Murale, Lavanya Gopala, Jun-Seok Lee

{"title":"Sensing and Imaging Agents for Cyclooxygenase Enzyme.","authors":"Subba Rao Cheekatla, Dhiraj P Murale, Lavanya Gopala, Jun-Seok Lee","doi":"10.1002/cmdc.202400636","DOIUrl":"10.1002/cmdc.202400636","url":null,"abstract":"In this concept, we present a comprehensive study on the development and application of COX-2-specific fluorescent probes for cancer imaging and diagnosis. To target cancer cells and measuring cancer-related activities in specific organelles quickly and accurately are crucial factors for early diagnosis and research on cancer pathology and treatment. This concept explores a variety of probes based on indomethacin (IMC), celecoxib, rofecoxib as well as CoxFluor and each one demonstrates unique mechanisms and high selectivity towards COX-2 enzymes. These probes were designed to enhance fluorescence upon binding to COX-2 which enable precise visualization of tumor and inflamed tissues. The research emphasizes the importance of COX-2 as a biomarker in cancer diagnostics, particularly in identifying cancer stem cells and inflamed tissues. This concept highlights the potentiality of these probes in non-invasive imaging techniques which offering significant advancements in cancer diagnosis and monitoring. The in vivo and in vitro experiments, including applications in mouse models and human tissue samples, confirm the efficacy of these probes in providing detailed imaging for clinical and research applications.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400636"},"PeriodicalIF":3.6,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491581","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 Truncated Cyclic Peptides Targeting an Induced-Fit Pocket on PCSK9. 发现靶向 PCSK9 上诱导拟合口袋的截短环肽。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-10-22 DOI: 10.1002/cmdc.202400208

Philipp Grosche, Alec N Flyer, Raphael Gattlen, Mei Xu, Andrei A Golosov, Victoria Vera, Stephanie Pickett, Margaret E Brousseau, Rajiv Chopra, Kevin B Clairmont, Alexander Koch, Eugene Liu, Patrick Reid, Lauren Perry, Lihua Yang, Qing Yang, Lauren G Monovich

{"title":"Discovery of Truncated Cyclic Peptides Targeting an Induced-Fit Pocket on PCSK9.","authors":"Philipp Grosche, Alec N Flyer, Raphael Gattlen, Mei Xu, Andrei A Golosov, Victoria Vera, Stephanie Pickett, Margaret E Brousseau, Rajiv Chopra, Kevin B Clairmont, Alexander Koch, Eugene Liu, Patrick Reid, Lauren Perry, Lihua Yang, Qing Yang, Lauren G Monovich","doi":"10.1002/cmdc.202400208","DOIUrl":"https://doi.org/10.1002/cmdc.202400208","url":null,"abstract":"Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates plasma low-density lipoprotein cholesterol (LDL-C) levels by promoting hepatic LDL receptor (LDL-R) degradation. We previously identified and optimized 13-mer cyclic peptides that bind to a novel, induced-fit pocket adjacent to the binding interface of PCSK9 and LDL-R and effectively disrupted the PCSK9/LDL-R protein-protein interaction (PPI) both in vitro and in vivo. However this series of large cyclic peptides required charged groups for function and lacked oral bioavailability in rodents. We describe herein multiple structure-based modifications to these original peptides to yield truncated, neutral molecules with full PPI function in both biochemical and cellular assays. In parallel, new mRNA-peptide display screens identified non-functional 8- and 9-mer compounds which ligand the induced-fit pocket in a distinct manner. Taken together, these studies indicate multiple directions to reduce the size and complexity of this peptide class toward a true small molecule oral agent.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400208"},"PeriodicalIF":3.6,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491519","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

Biosourced Au(III) Complexes from D-Xylose: Synthesis and Biological Evaluation. 来自 D-木糖的生物源 Au（III）配合物：合成与生物学评价。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-10-21 DOI: 10.1002/cmdc.202400565

Laura M H Pascual, Jérôme Devy, Marius Colin, Lise Chazée, Alexandra Guillaneuf, Béatrice Marin, Richard Plantier-Royon, Sylvain Gatard

引用次数: 0

Insights into Molecular Interactions and Biological Effect of Natural Stilbenoids at the TRPA1 Ion Channel. 洞察天然苯乙烯类化合物在 TRPA1 离子通道中的分子相互作用和生物效应

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-10-21 DOI: 10.1002/cmdc.202400501

Atefeh Saadabadi, Marja Rantanen, Parthiban Marimuthu, Ari-Pekka Koivisto, Patrik C Eklund, Outi M H Salo-Ahen

{"title":"Insights into Molecular Interactions and Biological Effect of Natural Stilbenoids at the TRPA1 Ion Channel.","authors":"Atefeh Saadabadi, Marja Rantanen, Parthiban Marimuthu, Ari-Pekka Koivisto, Patrik C Eklund, Outi M H Salo-Ahen","doi":"10.1002/cmdc.202400501","DOIUrl":"10.1002/cmdc.202400501","url":null,"abstract":"Natural stilbenoids, polyphenolic compounds notably found in Scots pine and Norway spruce, have been shown to exhibit analgesic and anti-inflammatory effects through the TRPA1 channel, making them promising hits for the development of novel agents to treat inflammatory diseases and pain. In this study, we computationally investigated the putative binding sites of natural stilbenoids at the TRPA1 channel. Specifically, we employed molecular docking and MD simulation approaches to explore three known ligand binding sites at TRPA1. Furthermore, the biological effect of the studied compounds on TRPA1 was assessed in vitro using a fluorescent imaging plate reader (FLIPR™) calcium assay. Our modeling results suggest the stilbenoids exhibit higher affinity to the two agonist binding sites than the antagonistic site. Consistent with this, the in vitro results showed that the stilbenoids act as moderate TRPA1 channel agonists and likely inhibit the channel through a desensitization mechanism rather than act as pure TRPA1 antagonists. Additionally, our bias-force pulling simulations proposed an additional binding pocket for the natural stilbenoids that is distinct from the known ligand binding sites at TRPA1. The results of the study give useful insights into structure-based design and development of novel therapeutic TRPA1 modulators.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400501"},"PeriodicalIF":3.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454110","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

Diversity Oriented Strategy (DOS) for the Efficient Synthesis of Benzofuro[2,3-b]pyridine Derivatives with Anticancer Activity. 高效合成具有抗癌活性的苯并呋喃并[2,3-b]吡啶衍生物的多样性导向策略 (DOS)。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-10-18 DOI: 10.1002/cmdc.202400514

Reymark Ereje, Jantana Yahuafai, Theeranuch Jaroenchuensiri, Patcharaporn Supakijjanusorn, Sukanya Unson, Borwornlak Toopradab, Thanyada Rungrotmongkol, Somsak Pianwanit, Chanat Aonbangkhen, Tanatorn Khotavivattana

{"title":"Diversity Oriented Strategy (DOS) for the Efficient Synthesis of Benzofuro[2,3-b]pyridine Derivatives with Anticancer Activity.","authors":"Reymark Ereje, Jantana Yahuafai, Theeranuch Jaroenchuensiri, Patcharaporn Supakijjanusorn, Sukanya Unson, Borwornlak Toopradab, Thanyada Rungrotmongkol, Somsak Pianwanit, Chanat Aonbangkhen, Tanatorn Khotavivattana","doi":"10.1002/cmdc.202400514","DOIUrl":"10.1002/cmdc.202400514","url":null,"abstract":"Benzofuropyridines (BFP) are polycyclic compounds with known applications in neuronal diseases. However, its derivatization patterns and anticancer potential remains unexplored. Leveraging the idea of diversity-oriented synthesis (DOS), we developed a highly efficient synthetic route for BFP, to increase the library of available analogs producing three compounds in one reaction set up, including the 2O-, 6O-, and the 1 N-substituted species, also synthesizing the unusual 2-pyridone derivatives. Key bromination reaction of the BFP moiety was successfully described which can widen the available variation in the compound's structure. The cytotoxic activity of the compounds was assessed against SH-SY5Y (neuroblastoma), HepG2 (hepatocellular carcinoma), Kb (human oral epidermoid), HeLa (cervical) and MCF-7 (breast) cancer cell lines. In the series, the m-bromobenzyl (5 b), methylcyano (5 g) and propargyl (5 h) 2O-derivatives demonstrated good selectivity against cancer cells with selectivity index (SI) of >71 for 5 g against HeLa over the normal cells, as compared to the standard drug, Doxorubicin (SI=6.7). The quantitative structure-activity relationship (QSAR) analysis revealed an impressive correlation of the defined descriptors with the bioactivity having an R2 value of 0.971 and 0.893 for Kb and HeLa respectively. Altogether, our work highlighted new information on the synthesis of BFP derivatives with potent cytotoxic activity.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400514"},"PeriodicalIF":3.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454109","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

Is it Time for Multi-Drug Therapy with Combination of Therapeutic Nucleic Acids? 现在是使用治疗性核酸组合进行多种药物治疗的时候了吗？

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-10-17 DOI: 10.1002/cmdc.202400493

Zbigniew J Leśnikowski

引用次数: 0

Synthesis, Characterization, and Biological Activity of New 4`-Functionalized Bis-Terpyridine Ruthenium(II) Complexes: Anti-inflammatory Activity Advances. 新型 4`官能化双三吡啶钌（II）配合物的合成、表征和生物活性：抗炎活性的进展。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-10-17 DOI: 10.1002/cmdc.202400680

Mohamed Elnagar, Khaled S Abou-El-Sherbini, Safia Samir, Walid Sharmoukh, Mohamed S Abdel-Aziz, Yasser M Shaker

{"title":"Synthesis, Characterization, and Biological Activity of New 4`-Functionalized Bis-Terpyridine Ruthenium(II) Complexes: Anti-inflammatory Activity Advances.","authors":"Mohamed Elnagar, Khaled S Abou-El-Sherbini, Safia Samir, Walid Sharmoukh, Mohamed S Abdel-Aziz, Yasser M Shaker","doi":"10.1002/cmdc.202400680","DOIUrl":"https://doi.org/10.1002/cmdc.202400680","url":null,"abstract":"Ruthenium complexes incorporating 2,2':6',2''-terpyridine ligands have emerged as promising candidates due to their versatile biological activities including DNA-binding, anti-inflammatory, antimicrobial, and anticancer properties. In this study, three novel 4'-functionalized bis(terpyridine) ruthenium (II) complexes were synthesized. These complexes feature one ligand as 4-(2,2':6',2''-terpyridine-4'-yl) benzoic acid and the second ligand as either 4'-(2-thienyl)-2,2':6',2''-terpyridine, 4'-(3,4-dimethoxyphenyl)-2,2':6',2''-terpyridine, or 4'-(4-dimethylaminophenyl)-2,2':6',2''-terpyridine. Besides the chemical characterization by 1H and 13C NMR, mass spectrometry, and absorption and emission spectroscopy, the complexes were tested for their biological activity as anti-inflammatory, anticancer, and antimicrobial agents. Moreover, the toxicity of the Ru(II) complexes was assessed and benchmarked against diclofenac potassium and ibuprofen using a haemolysis assay. Biological evaluations demonstrate that these ruthenium complexes exhibit promising therapeutic potential with reduced haemolytic activity compared to standard drugs. They demonstrate substantial anti-inflammatory effects through inhibition of albumin denaturation along with moderate cytotoxicity against cancer cell lines and broad-spectrum antimicrobial activity. These findings highlight the multifaceted biomedical applications of 4'-functionalized bis(terpyridine) ruthenium (II) complexes, suggesting their potential for further development as effective and safe therapeutic agents.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400680"},"PeriodicalIF":3.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454112","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

Cover Feature: The IMS Library: from IN-Stock to Virtual (ChemMedChem 20/2024) 封面专题：IMS 图书馆：从库存到虚拟（ChemMedChem 20/2024）

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-10-17 DOI: 10.1002/cmdc.202482002

Dr. Teodora Djikic-Stojsic, Guillaume Bret, Dr. Gaëlle Blond, Dr. Nicolas Girard, Dr. Clothilde Le Guen, Dr. Claire Marsol, Dr. Martine Schmitt, Séverine Schneider, Dr. Frederic Bihel, Dr. Dominique Bonnet, Dr. Mihaela Gulea, Prof. Dr. Esther Kellenberger

{"title":"Cover Feature: The IMS Library: from IN-Stock to Virtual (ChemMedChem 20/2024)","authors":"Dr. Teodora Djikic-Stojsic, Guillaume Bret, Dr. Gaëlle Blond, Dr. Nicolas Girard, Dr. Clothilde Le Guen, Dr. Claire Marsol, Dr. Martine Schmitt, Séverine Schneider, Dr. Frederic Bihel, Dr. Dominique Bonnet, Dr. Mihaela Gulea, Prof. Dr. Esther Kellenberger","doi":"10.1002/cmdc.202482002","DOIUrl":"https://doi.org/10.1002/cmdc.202482002","url":null,"abstract":"The cover represents an approach to creating a diverse chemical library with unique scaffolds. Combining the expertise of chemoinformaticians, organic synthetic chemists, and medicinal chemists, two libraries were developed. Starting with over 10000 in-stock compounds, the essential chemical library (eIMS) consists of 578 original and diverse compounds on plates, ready for high-throughput screening. Additionally, using chemoinformatics tools the virtual chemical library (vIMS) featuring 821070 unique, original, virtual compounds was created. This emphasized efficient hit-to-lead optimization, based on established synthetic pathways and medicinal chemistry guidelines. More details can be found in article 10.1002/cmdc.202400381 by Esther Kellenberger and co-workers. Cover design by Teodora Djikic-Stojsic.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture>\u0000 </div>\u0000 </figure>\u0000 ","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"19 20","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202482002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451220","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