ChemMedChem最新文献_第9页

Synthesis of trans-Fused 3,6-Anhydro Hexofuranose Frameworks via Catalytic Hydrogenolysis Triggered Debenzylative Intramolecular Acetalation 催化氢解引发脱苯缩分子内缩合反应合成反融合3,6-无水己糖框架。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-19 DOI: 10.1002/cmdc.202400907

Yu Li, Zhi-mei Wang, Wen-xiang Tao, Jian-chen Yang, Genzoh Tanabe, Osamu Muraoka, Wei Li, Wei-Jia Xie

引用次数: 0

Membrane Proteins in Nanodiscs: Methods and Applications 纳米圆盘中的膜蛋白：方法和应用。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-18 DOI: 10.1002/cmdc.202400775

Jiaxu Guo, Qinghan Hou, Yulin Tan, Ruoheng Fu, Xuanwei Huang, Prof. Chan Cao

引用次数: 0

Tumor Microenvironment-Responsive Multinucleated Nanocomplexes Loaded with Carbon Dots for Combined Photothermal/Chemodynamic Therapy of Breast Cancer 负载碳点的肿瘤微环境响应多核纳米复合物用于光热/化学动力联合治疗乳腺癌。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-16 DOI: 10.1002/cmdc.202400983

Zihan Zhu, Yan Zhang, Cui He, Yimin Jin, Wei Bian, Xinjing Tang, Jing Wang

引用次数: 0

“Cofactors” for Natural Products 天然产品的“辅助因子”。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-16 DOI: 10.1002/cmdc.202400498

Shao-Lun Chiou, Chin-Yuan Chang, John Chu

引用次数: 0

Resorcinol-based Bolaamphiphilic Quaternary Ammonium Compounds 间苯二酚基博拉两亲性季铵化合物。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-16 DOI: 10.1002/cmdc.202400932

Johanna Y. D. Asante, Caroline M. Casey, Elise L. Bezold, Asantha Fernando, Diana McDonough, William M. Wuest, Kevin P. C. Minbiole

{"title":"Resorcinol-based Bolaamphiphilic Quaternary Ammonium Compounds","authors":"Johanna Y. D. Asante, Caroline M. Casey, Elise L. Bezold, Asantha Fernando, Diana McDonough, William M. Wuest, Kevin P. C. Minbiole","doi":"10.1002/cmdc.202400932","DOIUrl":"10.1002/cmdc.202400932","url":null,"abstract":"Quaternary ammonium compounds (QACs) play crucial disinfectant roles in healthcare, industry, and domestic settings. Most commercially utilized QACs like benzalkonium chloride have a common architectural theme, leading to a rise in bacterial resistance and urgent need for novel structural classes. Some potent QACs such as chlorhexidine (CHX) and octenidine (OCT) feature a bolaamphiphilic architecture, comprised of two cationic centers at the molecular periphery and a non-polar region connecting them; these compounds show promise to elude bacterial resistance mechanisms. Inspired by such structures, we synthesized a series of 43 biscationic amphiphilic compounds focused on a resorcinol core, featuring flexibility of linker lengths, alkyl tails, and relative substituent positioning, to study their structure activity relationships (SARs). Antibacterial activity evaluation against a panel of gram-positive and gram-negative strains, including ESKAPE pathogens (A. baumannii, P. aeruginosa), were encouraging, with minimum inhibitory concentrations (MICs) of 0.5–4 μM against all tested strains for select compounds. Ten prepared compounds bearing either 17 or 18 total side chain carbons demonstrated uniformly strong antibacterial activity against P. aeruginosa (MIC 4–16 μM) and 6 other strains (MIC ≤4 μM), irrespective of cationic spacing. These findings promise to further extend the application of bolaamphiphilic QACs as a novel class of disinfectants.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996903","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

Expanding the Variety of Pyridinium-Based Bis-QACs with Antimicrobial Properties: Investigation into Linker Structure-Activity Correlation 扩展具有抗菌性能的吡啶基双qacs的种类：连接子构效关系的研究。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-16 DOI: 10.1002/cmdc.202400972

Nikita A. Frolov, Alexander A. Tyutin, Alexandra N. Tyurina, Mary A. Seferyan, Elena V. Detusheva, Elizabeth Son, Evgeniya A. Saverina, Anatoly N. Vereshchagin

{"title":"Expanding the Variety of Pyridinium-Based Bis-QACs with Antimicrobial Properties: Investigation into Linker Structure-Activity Correlation","authors":"Nikita A. Frolov, Alexander A. Tyutin, Alexandra N. Tyurina, Mary A. Seferyan, Elena V. Detusheva, Elizabeth Son, Evgeniya A. Saverina, Anatoly N. Vereshchagin","doi":"10.1002/cmdc.202400972","DOIUrl":"10.1002/cmdc.202400972","url":null,"abstract":"For decades quaternary ammonium compounds (QACs) have served as main component of a top antiseptic and disinfectant compositions. Among them, bis-QACs are the most prominent and effective class of biocides. Although mono-QACs still dominate the antiseptic market, their activity against Gram-negative bacteria is largely inferior to bis-QACs. Moreover, the new wave of bacterial resistance during the COVID-19 pandemic is threatening the efficiency of popular antiseptics. Therefore, the requirement for novel biocides is urgent. Reported here is a unified and simple two-step synthesis to achieve novel biocide's architectures with aromatic linkers. Thus, a series of 14 bis-QACs have been prepared using an Ullman-type reaction following by N-alkylation. The most prominent compounds showed strong bioactivity against a panel of nineteen microbial pathogens, multi-resistant bacterial ESKAPEE strains, fungi and biofilms, including strains, which acquired resistance during COVID-19 in 2021. Moreover, significant improvements in antibiofilm action were observed, where bis-QACs 5 c and 6 a outperformed gold standard pyridinium antiseptic octenidine. These findings will serve as a good basis for further studies of bis-QACs architectures as highly effective biocides.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996891","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

Total Synthesis of Antiausterity Agent Callistrilone O Reveals Promising Antitumor Activity in a Melanoma Homograft Mouse Model 抗肿瘤药物Callistrilone O的全合成在黑色素瘤同种移植小鼠模型中显示出有希望的抗肿瘤活性。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-15 DOI: 10.1002/cmdc.202400818

Kensuke Okuda, Akira Takagi, Ryohei Shimizu, Kensuke Nishi, Narumi Hayano, Ippei Takashima, Morichika Konishi

{"title":"Total Synthesis of Antiausterity Agent Callistrilone O Reveals Promising Antitumor Activity in a Melanoma Homograft Mouse Model","authors":"Kensuke Okuda, Akira Takagi, Ryohei Shimizu, Kensuke Nishi, Narumi Hayano, Ippei Takashima, Morichika Konishi","doi":"10.1002/cmdc.202400818","DOIUrl":"10.1002/cmdc.202400818","url":null,"abstract":"The antiausterity strategy in anticancer drug discovery has attracted much attention as a way to exterminate cancer cells under nutrient deprived conditions which are commonly found in solid tumors. These tumors under low nutrient stress are known to be malignant and often resist conventional drug therapy. As a potential drug candidate, we focused on the meroterpenoid natural product callistrilone O which has demonstrated extremely potent antiausterity properties toward PANC-1 pancreatic carcinoma in vitro. Here, we report for the first time the total synthesis of callistrilone O in seven steps from phloroglucinol. A Friedel-Crafts-type Michael addition and an oxidative [3+2] cycloaddition with Fetizon's reagent were used to construct the molecular skeleton. The preferential cytotoxicity of callistrilone O was also evaluated with multiple starvation-resistant cancer cell lines under low nutrient conditions. Furthermore, callistrilone O was found to strongly suppress B16 melanoma tumor growth without critical toxicity in vivo. Overall, this study presents a novel anticancer agent candidate from natural products with a concise synthetic route which can be readily applied to the synthesis of derivatives.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 7","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982158","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

Targeting Tumor-Associated Carbonic Anhydrases in Photothermal Therapy 特别收藏：法国光热治疗中靶向肿瘤相关碳酸酐酶的药物发现。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-14 DOI: 10.1002/cmdc.202400893

Prof. Dr. Sébastien Clément, Dr. Sébastien Richeter, Prof. Dr. Jean-Yves Winum

{"title":"Targeting Tumor-Associated Carbonic Anhydrases in Photothermal Therapy","authors":"Prof. Dr. Sébastien Clément, Dr. Sébastien Richeter, Prof. Dr. Jean-Yves Winum","doi":"10.1002/cmdc.202400893","DOIUrl":"10.1002/cmdc.202400893","url":null,"abstract":"Tumor-associated human carbonic anhydrases (hCAs), particularly isoforms hCA IX and hCA XII, are overexpressed in hypoxic regions of solid tumors and play a crucial role in regulating pH homeostasis, promoting cancer cell survival and enhancing invasiveness. These enzymes have emerged as promising therapeutic targets in cancer treatment, including photothermal therapy (PTT). PTT is a minimally invasive technique that uses light-absorbing agents to convert near-infrared (NIR) light into heat, effectively inducing localized hyperthermia and promoting cancer cell apoptosis. Recent advances in the design of hCA-targeted photothermal agents have shown promise in selectively targeting and ablating cancer cells while sparing healthy tissues. We explore here recent advancements in developing combination therapies that integrate hCA-targeted strategies with PTT for tumor treatment. By focusing on tumor-associated isoforms hCA IX and hCA XII, we underscore the potential of hCA inhibition to enhance both the efficacy and specificity of PTT in cancer therapy. We also address critical challenges and outline future directions, emphasizing the need to improve the biocompatibility, stability, and clinical translation of hCA-targeted photothermal agents. This mini review highlights the promise of combining hCA inhibition with PTT as an innovative therapeutic approach, aiming to advance more precise and effective cancer treatments.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202400893","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977019","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

Cover Feature: How Should we Teach Medicinal Chemistry in Higher Education to Prepare Students for a Future Career as Medicinal Chemists and Drug Designers? – A Teacher's Perspective (ChemMedChem 2/2025) 封面专题：我们应该如何在高等教育中教授药物化学，以使学生为未来的药物化学家和药物设计师做好准备？-教师的视角（ChemMedChem 2/2025）

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-14 DOI: 10.1002/cmdc.202580202

Philipp Klahn

引用次数: 0

Conformational Engineering of Flexible Protein Fragments on the Surface of Different Nanoparticles: The Surface-Atom Mobility Rules 不同纳米颗粒表面柔性蛋白片段的构象工程：表面-原子迁移规律。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-14 DOI: 10.1002/cmdc.202400832

Wenxian Zhao, Yiwei Sun, Laiyu Che, Haifang Wang, Aoneng Cao

{"title":"Conformational Engineering of Flexible Protein Fragments on the Surface of Different Nanoparticles: The Surface-Atom Mobility Rules","authors":"Wenxian Zhao, Yiwei Sun, Laiyu Che, Haifang Wang, Aoneng Cao","doi":"10.1002/cmdc.202400832","DOIUrl":"10.1002/cmdc.202400832","url":null,"abstract":"As a newly emerging technology, conformational engineering (CE) has been gradually displaying the power of producing protein-like nanoparticles (NPs) by tuning flexible protein fragments into their original native conformation on NPs. But apparently, not all types of NPs can serve as scaffolds for CE. To expedite the CE technology on a broader variety of NPs, the essential characteristic of NPs as scaffolds for CE needs to be identified. Herein, we investigate the potential of two distinct types of NPs as scaffolds for CE: CdSe/ZnS quantum dots (QDs), an ionic compound NP, and palladium NPs (PdNPs), a metal NP. The results demonstrate that while QDs cannot support the restoration of the native conformation and function of the complementary-determining region (CDR) fragments of antibodies, PdNPs can. The notably disparate outcomes unequivocally show that the mobility of the surface atoms/adatoms of the NPs or the mobility of the conjugating bonds to the NPs is essential for CE, which allows the conjugated peptides to undergo a conformational change from their initial random conformation to their most stable native conformation under the constraints mimicking the native long-range interactions in the original proteins. This discovery opens the door for CE on more NPs in the future.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982181","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