ChemMedChem最新文献_第10页

Tumor-Associated Carbohydrate Antigen 19-9 (CA 19-9), a Promising Target for Antibody-Based Detection, Diagnosis, and Immunotherapy of Cancer. 肿瘤相关碳水化合物抗原 19-9 (CA19-9)--基于抗体的癌症检测、诊断和免疫疗法的有望靶点。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-09-04 DOI: 10.1002/cmdc.202400491

Athar Nakisa, Lorenzo F Sempere, Xi Chen, Linda T Qu, Daniel Woldring, Howard C Crawford, Xuefei Huang

引用次数: 0

Zn(II)-Curcumin Complexes-Based Anticancer Agents. 基于 Zn(II)-curcumin 复合物的抗癌剂。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-09-03 DOI: 10.1002/cmdc.202400558

Rajdeep Mondal, Muthukumar Keerthana, Nanjan Pandurangan, Sankarasekaran Shanmugaraju

{"title":"Zn(II)-Curcumin Complexes-Based Anticancer Agents.","authors":"Rajdeep Mondal, Muthukumar Keerthana, Nanjan Pandurangan, Sankarasekaran Shanmugaraju","doi":"10.1002/cmdc.202400558","DOIUrl":"10.1002/cmdc.202400558","url":null,"abstract":"There is a great deal of research interest in the design of alternative metallodrugs to Pt(II)-derivatives for cancer treatment. The low solubility of such drugs in biological mediums leading to poor bioavailability is the major hurdle of several metal-based anticancer agents. These issues have recently been addressed by designing bio-active ligands based on metal-containing anticancer agents. Conjugating with bioactive ligands has significantly improved the bioavailability of the metallodrugs and their cancer cell targeting ability. One such naturally available bioactive ligand is curcumin. Until recently, several curcumin-based anticancer metallodrugs have been developed and successfully demonstrated for their anticancer studies. In this article, we aim to highlight, the synthesis, structure, and anticancer properties of various Zn(II)-curcumin-based coordination complexes. The effect of introducing different functional groups, targeting ligands, and photo-active ligands on the anticancer potential of such complexes has been mentioned in detail. The current status and future perspective on curcumin-based metallodrugs for cancer treatment have also been stated.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400558"},"PeriodicalIF":3.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118540","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

Fluorescence-Based HTS Assays for Ion Channel Modulation in Drug Discovery Pipelines. 基于荧光的 HTS 检测法，用于药物研发流程中的离子通道调节。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-09-02 DOI: 10.1002/cmdc.202400383

Jan Voldřich, Marika Matoušová, Markéta Šmídková, Helena Mertlíková-Kaiserová

{"title":"Fluorescence-Based HTS Assays for Ion Channel Modulation in Drug Discovery Pipelines.","authors":"Jan Voldřich, Marika Matoušová, Markéta Šmídková, Helena Mertlíková-Kaiserová","doi":"10.1002/cmdc.202400383","DOIUrl":"10.1002/cmdc.202400383","url":null,"abstract":"Ion channels represent a druggable family of transmembrane pore-forming proteins with important (patho)physiological functions. While electrophysiological measurement (manual patch clamp) remains the only direct method for detection of ion currents, it is a labor-intensive technique. Although automated patch clamp instruments have become available to date, their high costs limit their use to large pharma companies or commercial screening facilities. Therefore, fluorescence-based assays are particularly important for initial screening of compound libraries. Despite their numerous disadvantages, they are highly amenable to high-throughput screening and in many cases, no sophisticated instrumentation or materials are required. These features predispose them for implementation in early phases of drug discovery pipelines (hit identification), even in an academic environment. This review summarizes the advantages and pitfalls of individual methodological approaches for identification of ion channel modulators employing fluorescent probes (i. e., membrane potential and ion flux assays) with emphasis on practical aspects of their adaptation to high-throughput format.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400383"},"PeriodicalIF":3.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102575","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

Front Cover: Prodrug Approach to Exploit (S)-Alanine Amide as Arginine Mimic Moiety in the Development of Protein Arginine Methyltransferase 4 Inhibitors (ChemMedChem 17/2024) 封面：利用(S)-丙氨酸酰胺作为精氨酸模拟分子开发蛋白精氨酸甲基转移酶 4 抑制剂的原药方法（ChemMedChem 17/2024）

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-09-02 DOI: 10.1002/cmdc.202481701

Prof. Dr. Ciro Milite, Giuliana Sarno, Ida Pacilio, Dr. Agostino Cianciulli, Dr. Monica Viviano, Dr. Giulia Iannelli, Erica Gazzillo, Dr. Alessandra Feoli, Dr. Alessandra Cipriano, Prof. Dr. Maria Giovanna Chini, Prof. Dr. Sabrina Castellano, Prof. Dr. Giuseppe Bifulco, Prof. Dr. Gianluca Sbardella

{"title":"Front Cover: Prodrug Approach to Exploit (S)-Alanine Amide as Arginine Mimic Moiety in the Development of Protein Arginine Methyltransferase 4 Inhibitors (ChemMedChem 17/2024)","authors":"Prof. Dr. Ciro Milite, Giuliana Sarno, Ida Pacilio, Dr. Agostino Cianciulli, Dr. Monica Viviano, Dr. Giulia Iannelli, Erica Gazzillo, Dr. Alessandra Feoli, Dr. Alessandra Cipriano, Prof. Dr. Maria Giovanna Chini, Prof. Dr. Sabrina Castellano, Prof. Dr. Giuseppe Bifulco, Prof. Dr. Gianluca Sbardella","doi":"10.1002/cmdc.202481701","DOIUrl":"https://doi.org/10.1002/cmdc.202481701","url":null,"abstract":"The front cover picture shows that the introduction of a NAD(P)H:quinone oxidoreductase 1 (NQO1)-responsive trigger group (in cyan sticks) to mask the S-alanine amido group turns PRMT4 inhibitors (in orange sticks) into cell-permeable prodrugs, that after in cell activation (magenta) are able to inhibit PRMT4 (yellow green) and reduce arginine dimethylation of the PRMT4 substrates BRG1-associated factor 155 (BAF155). More details can be found in the Research Article by Maria Giovanna Chini, Sabrina Castellano, and co-workers. Cover design by Gianluca Sbardella.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture>\u0000 </div>\u0000 </figure>\u0000 ","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"19 17","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202481701","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142123174","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

Lactam Truncation Yields a Dihydroquinazolinone Scaffold with Potent Antimalarial Activity that Targets PfATP4. 内酰胺截短产生的二氢喹唑啉酮支架具有针对 PfATP4 的强效抗疟活性。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-08-30 DOI: 10.1002/cmdc.202400549

Trent D Ashton, Petar P S Calic, Madeline G Dans, Zi Kang Ooi, Qingmiao Zhou, Katie Loi, Kate E Jarman, Josephine Palandri, Deyun Qiu, Adele M Lehane, Bikash Maity, Nirupam De, Mufuliat T Famodimu, Michael J Delves, Emma Y Mao, Maria R Gancheva, Danny W Wilson, Mrittika Chowdury, Tania F de Koning-Ward, Delphine Baud, Stephen Brand, Paul F Jackson, Alan F Cowman, Brad E Sleebs

{"title":"Lactam Truncation Yields a Dihydroquinazolinone Scaffold with Potent Antimalarial Activity that Targets PfATP4.","authors":"Trent D Ashton, Petar P S Calic, Madeline G Dans, Zi Kang Ooi, Qingmiao Zhou, Katie Loi, Kate E Jarman, Josephine Palandri, Deyun Qiu, Adele M Lehane, Bikash Maity, Nirupam De, Mufuliat T Famodimu, Michael J Delves, Emma Y Mao, Maria R Gancheva, Danny W Wilson, Mrittika Chowdury, Tania F de Koning-Ward, Delphine Baud, Stephen Brand, Paul F Jackson, Alan F Cowman, Brad E Sleebs","doi":"10.1002/cmdc.202400549","DOIUrl":"10.1002/cmdc.202400549","url":null,"abstract":"The emergence of resistance against current antimalarial treatments has necessitated the need for the development of novel antimalarial chemotypes. Toward this goal, we recently optimised the antimalarial activity of the dihydroquinazolinone scaffold and showed it targeted PfATP4. Here, we deconstruct the lactam moiety of the tricyclic dihydroquinazolinone scaffold and investigate the structure-activity relationship of the truncated scaffold. It was shown that SAR between scaffolds was largely transferrable and generated analogues with potent asexual stage activity. Evaluation of the truncated analogues against PfATP4 mutant drug-resistant parasite strains and in assays measuring PfATP4-associated ATPase activity demonstrated retention of PfATP4 as the molecular target. Analogues exhibited activity against both male and female gametes and multidrug resistant parasites. Limited efficacy of analogues in a P. berghei asexual stage mouse model was attributed to their moderate metabolic stability and low aqueous stability. Further development is required to address these attributes toward the potential use of the dihydroquinazolinone class in a curative and transmission blocking combination antimalarial therapy.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400549"},"PeriodicalIF":3.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102576","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

How to Find a Fragment: Methods for Screening and Validation in Fragment-Based Drug Discovery. 如何寻找片段：基于片段的药物研发中的筛选和验证方法》（How Find the Fragment: Methods for Screening and Validation in Fragment-Based Drug Dscovery）。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-08-28 DOI: 10.1002/cmdc.202400342

Tim Kirkman, Catharina Dos Santos Silva, Manuela Tosin, Marcio Vinicius Bertacine Dias

引用次数: 0

The Role of Water Networks in Phosphodiesterase Inhibitor Dissociation and Kinetic Selectivity. 水网络在磷酸二酯酶抑制剂解离和动力学选择性中的作用

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-08-28 DOI: 10.1002/cmdc.202400417

Antoni R Blaazer, Abhimanyu K Singh, Lorena Zara, Pierre Boronat, Lady J Bautista, Steve Irving, Maciej Majewski, Xavier Barril, Maikel Wijtmans, U Helena Danielson, Geert Jan Sterk, Rob Leurs, Jacqueline E van Muijlwijk-Koezen, David G Brown, Iwan de Esch

{"title":"The Role of Water Networks in Phosphodiesterase Inhibitor Dissociation and Kinetic Selectivity.","authors":"Antoni R Blaazer, Abhimanyu K Singh, Lorena Zara, Pierre Boronat, Lady J Bautista, Steve Irving, Maciej Majewski, Xavier Barril, Maikel Wijtmans, U Helena Danielson, Geert Jan Sterk, Rob Leurs, Jacqueline E van Muijlwijk-Koezen, David G Brown, Iwan de Esch","doi":"10.1002/cmdc.202400417","DOIUrl":"https://doi.org/10.1002/cmdc.202400417","url":null,"abstract":"In search of new opportunities to develop Trypanosoma brucei phosphodiesterase B1 (TbrPDEB1) inhibitors that have selectivity over the off-target human PDE4 (hPDE4), different stages of a fragment-growing campaign were studied using a variety of biochemical, structural, thermodynamic, and kinetic binding assays. Remarkable differences in binding kinetics were identified and this kinetic selectivity was explored with computational methods, including molecular dynamics and interaction fingerprint analyses. These studies indicate that a key hydrogen bond between GlnQ.50 and the inhibitors is exposed to a water channel in TbrPDEB1, leading to fast unbinding. This water channel is not present in hPDE4, leading to inhibitors with a longer residence time. The computer-aided drug design protocols were applied to a recently disclosed TbrPDEB1 inhibitor with a different scaffold and our results confirm that shielding this key hydrogen bond through disruption of the water channel represents a viable design strategy to develop more selective inhibitors of TbrPDEB1. Our work shows how computational protocols can be used to understand the contribution of solvent dynamics to inhibitor binding, and our results can be applied in the design of selective inhibitors for homologous PDEs found in related parasites.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400417"},"PeriodicalIF":3.6,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078616","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

Substrate-Based Ligand Design for Phenazine Biosynthesis Enzyme PhzF. 基于底物的吩嗪生物合成酶 PhzF 配体设计

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-08-20 DOI: 10.1002/cmdc.202400466

Janosch Baumgarten, Philipp Schneider, Marie Thiemann, Moritz Zimmermann, Christina Diederich, Wulf Blankenfeldt, Conrad Kunick

{"title":"Substrate-Based Ligand Design for Phenazine Biosynthesis Enzyme PhzF.","authors":"Janosch Baumgarten, Philipp Schneider, Marie Thiemann, Moritz Zimmermann, Christina Diederich, Wulf Blankenfeldt, Conrad Kunick","doi":"10.1002/cmdc.202400466","DOIUrl":"10.1002/cmdc.202400466","url":null,"abstract":"The phenazine pyocyanin is an important virulence factor of the pathogen Pseudomonas aeruginosa, which is on the WHO list of antibiotic resistant \"priority pathogens\". In this study the isomerase PhzF, a key bacterial enzyme of the pyocyanin biosynthetic pathway, was investigated as a pathoblocker target. The aim of the pathoblocker strategy is to reduce the virulence of the pathogen without killing it, thus preventing the rapid development of resistance. Based on crystal structures of PhzF, derivatives of the inhibitor 3-hydroxyanthranilic acid were designed. Co-crystal structures of the synthesized derivatives with PhzF revealed spacial limitations of the binding pocket of PhzF in the closed conformation. In contrast, ligands aligned to the open conformation of PhzF provided more room for structural modifications. The intrinsic fluorescence of small 3-hydroxyanthranilic acid derivatives enabled direct affinity determinations using FRET assays. The analysis of structure-activity relationships showed that the carboxylic acid moiety is essential for binding to the target enzyme. The results of this study provide fundamental structural insights that will be useful for the design of PhzF-inhibitors.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400466"},"PeriodicalIF":3.6,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003196","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

Front Cover: Lysophosphatidic Acid Receptor 1 (LPA1) Antagonists as Potential Migrastatics for Triple Negative Breast Cancer (ChemMedChem 16/2024) 封面：溶血磷脂酸受体 1 (LPA1) 拮抗剂作为治疗三阴性乳腺癌的潜在迁移剂（ChemMedChem 16/2024）

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-08-20 DOI: 10.1002/cmdc.202481601

Dr. Wenjie Liu, Amr A. K. Mousa, Austin M. Hopkins, Yin Fang Wu, Dr. Kelsie L. Thu, Dr. Michael Campbell, Dr. Simon J. Lees, Dr. Rithwik Ramachandran, Dr. Jinqiang Hou

引用次数: 0

Two Step One-Pot Synthesis of 7-Azaindole Linked 1,2,3-Triazole Hybrids: In-Vitro and In-Silico Antimicrobial Evaluation. 7-azaindole 链接 1,2,3-triazole 杂交化合物的两步一步法合成：体外和硅内抗菌评估。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-08-18 DOI: 10.1002/cmdc.202400451

Kanika Sharma, Bajrang Lal, Ram Kumar Tittal, Kashmiri Lal, Lalit Vats, Ghule Vikas D

{"title":"Two Step One-Pot Synthesis of 7-Azaindole Linked 1,2,3-Triazole Hybrids: In-Vitro and In-Silico Antimicrobial Evaluation.","authors":"Kanika Sharma, Bajrang Lal, Ram Kumar Tittal, Kashmiri Lal, Lalit Vats, Ghule Vikas D","doi":"10.1002/cmdc.202400451","DOIUrl":"10.1002/cmdc.202400451","url":null,"abstract":"Herein, we report design, synthesis and characterization of a new library of 7-azaindole N-ethyl linked 1,2,3-triazoles containing ethylene as a spacer unit, and evaluation of all the synthesized compounds for their antimicrobial properties. Antibacterial potential was checked against two Gram positive (B. subtilis and S. aureus) and two Gram negative (E. coli and P. aeruginosa) bacterial strains while antifungal potential was assayed against two fungal strains (C. albicans and A. niger). All the tested compounds showed satisfactory antibacterial potency in comparison to reference drug ciprofloxacin with MIC values ranging from 0.0108 to 0.0432 μmol/mL. Interestingly, except two, all the target compounds showed better antifungal property as compared to the reference drug fluconazole with MIC values less than 0.0408 μmol/mL. One of the compounds exhibited two-fold better antifungal potential in comparison to fluconazole. Furthermore, in-silico ADMET and DFT studies reported drug likeness behavior and chemical reactivity parameters, respectively. The cytotoxicity results on substrate azide 3 and most potent 1,2,3-triazoles (5 d and 5 l) were found to be non-toxic.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400451"},"PeriodicalIF":3.6,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999029","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