ChemMedChem最新文献_第8页

Design of a Long-Acting Morphine Prodrug for Safe Opioid Delivery 用于阿片类药物安全输送的长效吗啡前药的设计。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-08-18 DOI: 10.1002/cmdc.202500499

Hana S. Alhamadsheh, Roshanak Rahimian, Miki Park, Mamoun M. Alhamadsheh, Hala Aldawod

引用次数: 0

Novel Indoline Derivatives as Ferroptosis Inhibitors: Synthesis, Biological Evaluation, and Mechanistic Investigation 新型吲哚啉衍生物作为铁下垂抑制剂：合成、生物学评价和机制研究。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-08-18 DOI: 10.1002/cmdc.202500487

Wen Shao, Yuanyuan Liu, Deling Jiang, Zhiyang Xing, Jiale Qiao, Man Liu, Xupeng Huang, Renyu Zhang, Yuying Fang, Wei Peng

{"title":"Novel Indoline Derivatives as Ferroptosis Inhibitors: Synthesis, Biological Evaluation, and Mechanistic Investigation","authors":"Wen Shao, Yuanyuan Liu, Deling Jiang, Zhiyang Xing, Jiale Qiao, Man Liu, Xupeng Huang, Renyu Zhang, Yuying Fang, Wei Peng","doi":"10.1002/cmdc.202500487","DOIUrl":"10.1002/cmdc.202500487","url":null,"abstract":"Ferroptosis, a form of regulated cell death characterized by excessive lipid peroxidation, has been implicated in various neurological disorders. Ferrostatin-1 (Fer-1), a well-known ferroptosis inhibitor, exhibits therapeutic potential but suffers from poor metabolic stability, limiting its applications. In this study, a phenotype-based screening of an in-house compound library is conducted and a novel ferroptosis inhibitor, TJC-2-1, is identified. To optimize its inhibitory activity, a series of 35 indoline derivatives are synthesized and evaluated. Among them, compound 14 exhibits the most potent inhibition against erastin-induced (EC50 = 0.15 μM) and RSL3-induced (EC50 = 0.15 μM) ferroptosis in HT22 mouse hippocampal cells. Mechanistic investigations reveal that compound 14 functions as a novel radical-trapping antioxidant, exhibiting lipid peroxidation scavenging capacity comparable to that of Fer-1. Remarkably, compound 14 demonstrates significantly improved microsomal metabolic stability compared to Fer-1. These findings suggest that compound 14 has the potential to serve as a lead compound for ferroptosis-related diseases.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 17","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870577","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

Protocatechuic Acid and its Derivatives: Synthesis, Antioxidant Properties, and Potential In Vivo Wound Healing Applications 原儿茶酸及其衍生物：合成、抗氧化性能和潜在的体内伤口愈合应用。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-08-18 DOI: 10.1002/cmdc.202500280

Sumit Maurya, Sumit Manna, Mala Singh, Dharmendra Singh, Malay Nayak, Sudip Mukherjee, Arunava Manna

{"title":"Protocatechuic Acid and its Derivatives: Synthesis, Antioxidant Properties, and Potential In Vivo Wound Healing Applications","authors":"Sumit Maurya, Sumit Manna, Mala Singh, Dharmendra Singh, Malay Nayak, Sudip Mukherjee, Arunava Manna","doi":"10.1002/cmdc.202500280","DOIUrl":"10.1002/cmdc.202500280","url":null,"abstract":"Treatment of chronic wounds is a potential healthcare problem, affecting people globally. Traditional methods of wound healing are prone to several limitations, like infections, oxidative stress, and development of secondary wounds. Management of oxidative stress is an interesting platform to deal with chronic wounds. For this study, novel derivatives of protocatechuic acid, a naturally occurring phenolic acid, were designed by modifying the carboxylic acid moiety while preserving the hydroxyl groups for radical scavenging. So, a series of amide conjugates were synthesized by incorporating various amine moieties. Glucose conjugates were obtained through both click chemistry and direct coupling strategies and a chlorinated derivative was also prepared. The antioxidant potential of the compounds was screened using DPPH assay, followed by in vitro DCFDA assay on HEK-293T cell line. Top 5 lead molecules were checked for biocompatibility through MTT assay, which provided us with top 2 leads, Compounds 12 and 17 which were examined for a wound healing study on Wistar rats along with the starting compound 1. It was observed that Compound 17 demonstrated excellent wound tissue regeneration on day 12, as compared to the control group, suggesting the promising role of triazole and glucose moieties conjugation for relieving oxidative stress and wound management.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 18","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870578","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

Harnessing Chemical Diversity to Disarm Bacterial Communication for 25 Years: Natural Products, Repurposed Drugs, Peptides, and Synthetic Quorum Sensing Inhibitors 利用化学多样性解除细菌交流25年：天然产物，重新利用药物，肽和合成群体感应抑制剂。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-08-13 DOI: 10.1002/cmdc.202500477

Tung Truong-Thanh, Anh Nguyen Phuong, Linh Nguyen Khanh, Duc Nguyen Minh

{"title":"Harnessing Chemical Diversity to Disarm Bacterial Communication for 25 Years: Natural Products, Repurposed Drugs, Peptides, and Synthetic Quorum Sensing Inhibitors","authors":"Tung Truong-Thanh, Anh Nguyen Phuong, Linh Nguyen Khanh, Duc Nguyen Minh","doi":"10.1002/cmdc.202500477","DOIUrl":"10.1002/cmdc.202500477","url":null,"abstract":"Quorum sensing, a bacterial communication pathway, has emerged as a promising target for the development of alternative antimicrobial agents in the battle against bacterial resistance. In addition to biological investigations of quorum sensing mechanisms, substantial efforts have been made towards the rational design, synthesis, identification of natural products, and screening of commercial drugs towards this target. There are several individual reviews on the discovery of quorum sensing inhibitors; however, there has yet to be a comprehensive, detailed, and critical review providing a complete overview of the development of novel quorum sensing inhibitors, ranging from natural compounds, peptides, and repurposed drugs to synthetic molecules. This review provides a comprehensive and critical overview of quorum sensing inhibitors, highlighting key advances in their discovery, structure–activity relationships, and mechanisms of action over the past 25 years (2000–2025). It emphasizes several FDA-approved drugs (e.g., azithromycin, ciprofloxacin, and paracetamol), natural compounds (e.g., ajoene, curcumin, quercetin, and carvacrol), peptides, and synthetic libraries that exhibit potent anti-QS and antibiofilm activities against pathogenic bacteria. Furthermore, a systematic structural comparison and potential strategies for developing next-generation therapeutics based on current advancements will be discussed.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 18","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843922","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

Benzoxazoles Derived from Eugenol as Potential Agents against Arboviruses: Synthesis, Antiviral Studies, and Mechanistic Insights 从丁香酚中提取的苯并恶唑作为虫媒病毒的潜在药物：合成、抗病毒研究和机制见解。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-08-12 DOI: 10.1002/cmdc.202500323

Vinícius Augusto Campos Péret, Adriana Cotta Cardoso Reis, Lívia da Cunha Agostini, Isadora Oliveira Ansaloni Pereira, Glenda Nicioli da Silva, Diogo Teixeira Carvalho, Stefânia Neiva Lavorato, Saulo Fehelberg Pinto Braga, Geraldo Célio Brandão, Thiago Belarmino de Souza

{"title":"Benzoxazoles Derived from Eugenol as Potential Agents against Arboviruses: Synthesis, Antiviral Studies, and Mechanistic Insights","authors":"Vinícius Augusto Campos Péret, Adriana Cotta Cardoso Reis, Lívia da Cunha Agostini, Isadora Oliveira Ansaloni Pereira, Glenda Nicioli da Silva, Diogo Teixeira Carvalho, Stefânia Neiva Lavorato, Saulo Fehelberg Pinto Braga, Geraldo Célio Brandão, Thiago Belarmino de Souza","doi":"10.1002/cmdc.202500323","DOIUrl":"10.1002/cmdc.202500323","url":null,"abstract":"The synthesis of new eugenol-benzoxazole derivatives and their antiviral evaluation against Orthoflavivirus zikaense (ZIKV), Alphavirus chikungunya (CHIKV), and Alphavirus mayaro (MAYV) are reported. Derivative 16 shows the highest potency and selectivity indices: 25 for ZIKV (EC50: 6.1 µM), 11 for CHIKV (EC50: 14.2 µM), and 24 for MAYV (EC50: 6.3 µM), 68 times more potent than ribavirin and amantadine drugs. RT-qPCR showed that benzoxazole 16 reduced the viral load of CHIKV after 24 and 48 h and of ZIKV after 24 h, demonstrating that it may be a promising antiviral agent. In cytopathic effect assays, benzoxazoles 16 and 23 showed cell monolayer protection against ZIKV and compounds 16 and 24 against CHIKV. None of these compounds showed virucidal activity, suggesting they act post-viral entry, targeting proteins related to viral replication rather than inactivating the virus before cellular infection. Molecular dynamics and MM/GBSA binding energy analysis of compound 16 on viral replication targets identified the capsid protein and nsP3 as the most promising targets, with binding free energies of −31.21 and −29.55 kcal/mol, respectively. The ligand remained deeply buried and well-confined in both binding sites, with minimal positional drift and a marked reduction in solvent-accessible surface area.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 20","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820252","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

Cytotoxic, Antibacterial, and in Silico Pks13 Inhibitory Properties of Indole-Coupled Dihydrobenzo[c]phenanthridines 吲哚偶联二氢苯并[c]菲菲啶的细胞毒、抗菌和硅基Pks13抑制性能。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-08-11 DOI: 10.1002/cmdc.202500146

Reyna Martha Gallegos-Alvarado, Adriana Romo-Pérez, Luis Demetrio Miranda, María del Rayo Camacho-Corona, Alfonso Dueñas-González, Johannes Kirchmair, Abraham García

{"title":"Cytotoxic, Antibacterial, and in Silico Pks13 Inhibitory Properties of Indole-Coupled Dihydrobenzo[c]phenanthridines","authors":"Reyna Martha Gallegos-Alvarado, Adriana Romo-Pérez, Luis Demetrio Miranda, María del Rayo Camacho-Corona, Alfonso Dueñas-González, Johannes Kirchmair, Abraham García","doi":"10.1002/cmdc.202500146","DOIUrl":"10.1002/cmdc.202500146","url":null,"abstract":"The indoles and benzo[c]phenanthridines have attracted much interest as potential anticancer and antibacterial agents. Herein, the synthesis and bioactivity of new and known indole-coupled dihydrobenzo[c]phenanthridines are reported. Among the investigated compounds, 2j displays potent and selective activity against drug-resistant Staphylococcus aureus, S. epidermidis, and Enterococcus faecium strains. In addition, 1a-c and 2a specifically target the multidrug-resistant Mycobacterium tuberculosis G122, possibly by inhibiting the Pks13 enzyme, as deduced from the in silico analyses. Additionally, compound 1g is more potent than cisplatin against MCF-7 (breast) and PC-3 (prostate) human cancer cell lines, whereas 2b is found to be almost as active as cisplatin against PC-3 and SW-480 (colorectal) cell lines. Compounds 1a and 1g display remarkable selectivity index values, thus being promising antibacterial and anticancer hits.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 17","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820253","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 Fluorinated Pyrazolidine-3,5-Diones for Positron Emission Tomography Imaging of the P2Y12 Receptor in the Central Nervous System 氟化吡唑烷-3,5-二酮在中枢神经系统P2Y12受体正电子发射断层成像中的应用

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-08-11 DOI: 10.1002/cmdc.202500483

E. Johanna L. Stéen, Anne van der Schatte Olivier, Berend van der Wildt, Pedro Pereira, Khaled Alkayal, Leopoldo J. Gabella Carena, Robert C. Schuit, Mariska Verlaan, Wissam Beaino, Barbara A. Zarzycka, Iwan J. P. de Esch, Albert D. Windhorst

{"title":"Exploration of Fluorinated Pyrazolidine-3,5-Diones for Positron Emission Tomography Imaging of the P2Y12 Receptor in the Central Nervous System","authors":"E. Johanna L. Stéen, Anne van der Schatte Olivier, Berend van der Wildt, Pedro Pereira, Khaled Alkayal, Leopoldo J. Gabella Carena, Robert C. Schuit, Mariska Verlaan, Wissam Beaino, Barbara A. Zarzycka, Iwan J. P. de Esch, Albert D. Windhorst","doi":"10.1002/cmdc.202500483","DOIUrl":"10.1002/cmdc.202500483","url":null,"abstract":"The purinergic receptor P2Y12 (P2Y12R) has emerged as a promising biomarker for selectively imaging the anti-inflammatory phenotype of microglia. Developing positron emission tomography (PET) tracers for this target is an active area of research, as imaging of specific microglial phenotypes can provide valuable insights into their dynamics in neuroinflammation. A key challenge is identifying high affinity P2Y12R ligands with optimal properties for targeting this receptor in the central nervous system (CNS). Herein, the synthesis and evaluation of a series of fluorinated pyrazolidine-3,5-dione derivatives are conducted as potential P2Y12R PET tracers, designed based on a literature compound with promising physicochemical properties for brain permeability. All synthesized derivatives exhibit strong affinity for the human P2Y12R in vitro, with Ki values ranging from 1.21 to 5.66 nM. One candidate is selected for radiolabeling with fluorine-18 ([18F]8) and evaluated in healthy rats using dynamic PET imaging, as well as ex vivo biodistribution and metabolism studies. Unfortunately, [18F]8 shows low brain uptake, potentially due to deprotonation of the pyrazolidine-3,5-dione scaffold in vivo, in addition to a rapid metabolism. These findings highlight the need for novel chemical entities as starting points for tracer development to target the P2Y12R in the CNS.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 17","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820254","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

Structure Modification of FXR Antagonistic Chalcones and Their Inhibitory Effects on NSCLC Cell Proliferation and Metastasis FXR拮抗查尔酮的结构修饰及其对非小细胞肺癌细胞增殖和转移的抑制作用

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-08-08 DOI: 10.1002/cmdc.202500625

引用次数: 0

Structure-Based Drug Design of Novel Heterocyclic Scaffolds as TgCDPK1 Inhibitors 基于结构的新型杂环支架TgCDPK1抑制剂药物设计。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-08-08 DOI: 10.1002/cmdc.202500440

Anoopjit Singh Kooner, Mariah Norman, Igi Vilza, Michael P. Mannino, Mary Savari Dhason, Jon Helander, Shrushti Patil, L. David Sibley, James W. Janetka

引用次数: 0

Progress In the Chemistry and Pharmacology of Isoindolin-1-One Scaffolds 异吲哚-1- 1支架的化学和药理学研究进展。

IF 3.4 4区医学

ChemMedChem Pub Date : 2025-08-06 DOI: 10.1002/cmdc.202500420

Kunal Madaan, Ram Singh

{"title":"Progress In the Chemistry and Pharmacology of Isoindolin-1-One Scaffolds","authors":"Kunal Madaan, Ram Singh","doi":"10.1002/cmdc.202500420","DOIUrl":"10.1002/cmdc.202500420","url":null,"abstract":"Isoindolin-1-one scaffolds have emerged as privileged structures in medicinal and synthetic chemistry due to their diverse biological activities and synthetic accessibility. This review comprehensively highlights the recent advancements in the development of synthetic methodologies for constructing isoindolin-1-one cores, encompassing both metal-catalyzed and metal-free approaches. Key strategies include the electrochemical method, transition metal-catalyzed synthesis, radical and oxidant-driven metal-free method, acid-catalyzed and multicomponent method, ring opening method, and ultrasound-assisted method of synthesis. The flexibility of these methods arises from the wide range of starting materials, such as benzamides, imidates, nitriles, and aziridines, and the effective use of catalysts and additives, including Rh(III), Pd(II), Ru(II), Ag2CO3, CO, and various oxidants. This review also explores the structure–activity relationships of isoindolin-1-one derivatives in diverse therapeutic areas. Specific functional groups and substituents have been shown to enhance anticancer, antiviral, antipsychotic, antimicrobial, cardiovascular, anti-inflammatory, and antidiabetic activities. Modifications including lipophilic, electron-withdrawing, polar, and heterocyclic moieties have significantly improved biological efficacy, target specificity, and pharmacokinetics. The integration of these structural variations underscores the scaffold's versatility and its potential in drug discovery. This review aims to provide a consolidated foundation for future research on isoindolin-1-one based therapeutics and their strategic synthesis.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"20 17","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793062","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