IF 3.6 4区医学

ChemMedChem Pub Date : 2024-11-19 DOI: 10.1002/cmdc.202400525

Andrii S Myshko, Galyna P Mrug, Svitlana P Bondarenko, Bohdan A Demydchuk, Oleksandr L Kobzar, Vladyslav M Buldenko, Andriy I Vovk, Mykhaylo Frasinyuk

引用次数: 0

An interdisciplinary approach provides insights into the pronounced selectivity of compound 42 for DPP9. 跨学科方法为化合物 42 对 DPP9 的明显选择性提供了见解。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-11-18 DOI: 10.1002/cmdc.202400700

Olivier Beyens, Sam Corthaut, Anne-Marie Lambeir, Pieter Van Der Veken, Yann G-J Sterckx, Ingrid De Meester, Hans De Winter

引用次数: 0

A Pleiotropic Nanomedicine Mitigates Splenic Hyperplasia, Ineffective Erythropoiesis, G6PDH Anomaly through Redox Buffering in Preclinical Mice Model. 一种多效纳米药物通过氧化还原缓冲作用减轻临床前小鼠模型的脾脏增生、红细胞生成障碍和 G6PDH 异常。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-11-15 DOI: 10.1002/cmdc.202400698

Monojit Das, Susmita Mondal, Ria Ghosh, Lopamudra Roy, Anjan Kumar Das, Siddhartha Sankar Bhattacharya, Debasish Pal, Debasish Bhattacharya, Prantar Chakrabarti, Asim Kumar Mallick, Jayanta Kumar Kundu, Samir Kumar Pal

{"title":"A Pleiotropic Nanomedicine Mitigates Splenic Hyperplasia, Ineffective Erythropoiesis, G6PDH Anomaly through Redox Buffering in Preclinical Mice Model.","authors":"Monojit Das, Susmita Mondal, Ria Ghosh, Lopamudra Roy, Anjan Kumar Das, Siddhartha Sankar Bhattacharya, Debasish Pal, Debasish Bhattacharya, Prantar Chakrabarti, Asim Kumar Mallick, Jayanta Kumar Kundu, Samir Kumar Pal","doi":"10.1002/cmdc.202400698","DOIUrl":"10.1002/cmdc.202400698","url":null,"abstract":"Here, we present a pleiotropic nanomedicine-a smart, functionalized redox buffering nanoparticle-that may be used to treat hematological diseases, associated splenic hyperplasia, and issues related to restricted erythropoiesis. With a diameter of 5-7 nm, the spherical nanomaterial is made of manganese oxide and citrate. Here, we have produced the novel nanomaterial and, using cutting-edge electron microscopic and spectroscopic techniques, extensively assessed its redox buffering potential in vitrowith its structural integrity. Using an appropriate animal model (phenyl hydrazine, PHz, intoxicated C57BL/6J mice), we assessed the therapeutic efficacy of the redox buffering nanomedicine in the treatment of anemia and related consequences. We have further investigated the intricate molecular mechanism of the nanomedicine and its therapeutic impact, which includes increased erythropoiesis and G6PDH production, decreased inflammatory responses, mitigation of splenic hyperplasia, and synergistic intracellular redox-buffering. To the best of our knowledge, our studies would find relevance in the innovative management of anemia, decreased erythropoiesis, and splenic hyperplasia.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400698"},"PeriodicalIF":3.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613361","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

[18F]NP3-627, a candidate PET imaging agent targeting the NLRP3 inflammasome in the central nervous system. [18F]NP3-627，一种靶向中枢神经系统 NLRP3 炎症小体的 PET 成像候选药物。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-11-14 DOI: 10.1002/cmdc.202400816

David Michael Whitehead, Christian Fischer, Emmanuelle Briard, Christopher Farady, Nadège Graveleau, Joel Karrer, Klemens Kaupmann, Guillaume Lapointe, Angela Mackay, Lisa Reichert, Michael Wright, Linjing Mu, Yves P Auberson

{"title":"[18F]NP3-627, a candidate PET imaging agent targeting the NLRP3 inflammasome in the central nervous system.","authors":"David Michael Whitehead, Christian Fischer, Emmanuelle Briard, Christopher Farady, Nadège Graveleau, Joel Karrer, Klemens Kaupmann, Guillaume Lapointe, Angela Mackay, Lisa Reichert, Michael Wright, Linjing Mu, Yves P Auberson","doi":"10.1002/cmdc.202400816","DOIUrl":"https://doi.org/10.1002/cmdc.202400816","url":null,"abstract":"We describe the identification of a candidate positron emission tomography (PET) imaging agent for the NLRP3 protein. NLRP3 plays a critical role in the immune system and has proven a difficult target for the development of imaging agents due to its low and cell-specific expression profile. A recently described series of pyridazine-based inhibitors, with improved permeability and brain-penetration properties, was used as a starting point for the development of a suitable PET imaging agent. Optimization of affinity, non-specific binding and pharmacokinetic properties led to the identification of aminopyridazine (R)-2-(6-((1-cyclopropylpiperidin-3-yl)amino)pyridazin-3-yl)-5-fluoro-3-methylphenol (17b), which meets the preclinical profile of a successful imaging agent, and whose tritiated version demonstrated excellent specificity in a radioligand saturation binding assay, confirming its imaging potential.18F labeling led to [18F]NP3-627, the proposed PET imaging agent.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400816"},"PeriodicalIF":3.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613360","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

Biocatalytic Amino Acid Functionalisation. 生物催化氨基酸功能化。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-11-14 DOI: 10.1002/cmdc.202400628

Mark R Petchey, Pascal Schneider, Lucy A Harwood

引用次数: 0

Structure-Activity-Relationships of the Stability of six Pentathiepins towards Glutathione: Possible Correlations with Biological Activities. 六种五硫杂环戊烷对谷胱甘肽稳定性的结构-活性-关系：与生物活性的可能关联。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-11-11 DOI: 10.1002/cmdc.202400727

Martin Napierkowski, Tom Schöne, Siva Sankar Murthy Bandaru, Jo Judernatz, Lukas Schulig, Louis Schmidt, Carola Schulzke, Patrick Bednarski

{"title":"Structure-Activity-Relationships of the Stability of six Pentathiepins towards Glutathione: Possible Correlations with Biological Activities.","authors":"Martin Napierkowski, Tom Schöne, Siva Sankar Murthy Bandaru, Jo Judernatz, Lukas Schulig, Louis Schmidt, Carola Schulzke, Patrick Bednarski","doi":"10.1002/cmdc.202400727","DOIUrl":"https://doi.org/10.1002/cmdc.202400727","url":null,"abstract":"The biological properties of pentathiepins have been intensively studied in recent years. Although the proposed mechanism of action requires activation by intracellular thiols, the dependence of activity on the stability of pentathiepins towards glutathione (GSH) has not been directly investigated. Here, we determined the structure-related stability of six different pentathiepins with four different scaffolds in the presence of GSH by using reversed-phase high-performance liquid chromatography (RP-HPLC) and UV-vis spectroscopy over a wide range of GSH concentrations. We found significant differences in compound stability depending on the pentathiepin scaffold; these differences were reflected in their cytotoxic activities. However, we found no substantial differences in their inhibition of glutathione peroxidase 1 (GPx-1). While the intact pentathiepin ring is necessary for the antiproliferative activity of pentathiepins, the depletion of intracellular GSH content with dl-buthionine-(S,R)-sulfoximine (BSO) led to a significant increase in cytotoxicity of the tested substances. In view of the increased cytotoxicity following artificial GSH depletion, this calls into question the sole role of GSH in the intracellular activation mechanism.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400727"},"PeriodicalIF":3.6,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613369","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

New Indole-based Phenylthiazolyl-2,4-dihydropyrazolones as Tubulin polymerization inhibitors: Multicomponent synthesis, cytotoxicity evaluation, and in silico studies. 作为微管蛋白聚合抑制剂的新型吲哚基苯基噻唑-2,4-二氢吡唑酮：多组分合成、细胞毒性评估和硅学研究。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-11-10 DOI: 10.1002/cmdc.202400817

Bulti Bakchi, Geetanjali Devabattula, Sarvan Maddipatla, Anuradha Singampalli, Dileep Kumar Porna, Srinivas Nanduri, Anamika Sharma, Chandraiah Godugu, Venkata Madhavi Yaddanapudi

{"title":"New Indole-based Phenylthiazolyl-2,4-dihydropyrazolones as Tubulin polymerization inhibitors: Multicomponent synthesis, cytotoxicity evaluation, and in silico studies.","authors":"Bulti Bakchi, Geetanjali Devabattula, Sarvan Maddipatla, Anuradha Singampalli, Dileep Kumar Porna, Srinivas Nanduri, Anamika Sharma, Chandraiah Godugu, Venkata Madhavi Yaddanapudi","doi":"10.1002/cmdc.202400817","DOIUrl":"https://doi.org/10.1002/cmdc.202400817","url":null,"abstract":"A facile multicomponent synthesis of new indole-based phenylthiazolyl-dihydropyrazolone hybrids, their structural characterization, biological evaluation, and in silico investigations as anticancer agents are reported. Lead molecule 5i of the series showed potent activity against MCF-7 breast cancer cells with an IC50 of 3.92 ± 0.01 µM while showing minimal toxicity to normal human lung cells (IC50 = 69.85 ± 3.95 µM). Further studies show that the compound exhibits antiproliferative activity by inducing apoptosis in MCF-7 cancer cells. The wound healing assay indicated impaired cell migration under the concentration-dependent dosage. The lead molecule 5i also successfully inhibited the tubulin polymerase enzyme with an IC50 of 4.16 ± 0.18 µM. A flow cytometric assay indicated compound 5i induced apoptosis through G0 phase cell cycle arrest. The binding mode and interactions of the compound with the tubulin were predicted by molecular modelling and calculating binding free energies. These findings explain the current series as a new class of microtubule polymerization inhibitors with anticancer activity suitable for developing anticancer agents targeting tubulin.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400817"},"PeriodicalIF":3.6,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613366","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

Synthesis and evaluation of fluorinated piperazine-hydroxyethylamine analogues as potential antiplasmodial candidates. 作为潜在抗疟候选药物的氟化哌嗪-羟乙基胺类似物的合成与评估。

IF 3.6 4区医学

ChemMedChem Pub Date : 2024-11-08 DOI: 10.1002/cmdc.202400616

Charu Upadhyay, Shreya Bhattacharya, Sumit Kumar, Kapil Vashisht, Xujie Zhang, Dominic Gagnon, Pooja Singh, Peng Zhan, Dave Richard, Brijesh Rathi, Agam Prasad Singh, Priyamvada Singh

{"title":"Synthesis and evaluation of fluorinated piperazine-hydroxyethylamine analogues as potential antiplasmodial candidates.","authors":"Charu Upadhyay, Shreya Bhattacharya, Sumit Kumar, Kapil Vashisht, Xujie Zhang, Dominic Gagnon, Pooja Singh, Peng Zhan, Dave Richard, Brijesh Rathi, Agam Prasad Singh, Priyamvada Singh","doi":"10.1002/cmdc.202400616","DOIUrl":"https://doi.org/10.1002/cmdc.202400616","url":null,"abstract":"In this manuscript, twenty-one novel fluorinated piperazine-hydroxyethylamine analogues were synthesized and tested against Plasmodium falciparum (Pf). Among tested compounds, two 13g and 14g exhibited promising inhibitory activity on Pf3D7 with IC50 values of 0.28 and 0.09 µM, respectively. Neither of the hits exhibited cytotoxicity on HepG2 cells up to 150 µM and Vero cells up to 20 µM. Compounds 13g and 14g were also evaluated against chloroquine-resistant PfDd2 and displayed IC50 values of 0.11 and 0.10 µM, respectively. Next, 13g and 14g were administered to the Plasmodium berghei mice model at 30mg/kg intraperitoneally for four consecutive doses, which showed 25% and 50% reduction in the parasitemia load, respectively. The efficacy of hits 13g and 14g was improved along with mean survival time when administered in combination with artesunate. On liver-stage parasites, compounds 13g and 14g showed >90% inhibition at 1µM. Compound 14g was also tested for toxicity in mice at 100 mg/kg dose, which revealed no abnormality in mice organs. Preliminary pharmacokinetic studies of compound 14g exhibited absorption and maintained a presence in the body for more than six hours.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400616"},"PeriodicalIF":3.6,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613370","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: Facile Access to Structurally Diverse Antimalarial Indoles Using a One-Pot A3 Coupling and Domino Cyclization Approach (ChemMedChem 17/2023) 封面:使用一锅A3偶联和多米诺环化方法轻松获取结构多样的抗疟吲哚(ChemMedChem 17/2023)

IF 3.4 4区医学

ChemMedChem Pub Date : 2023-09-01 DOI: 10.1002/cmdc.202300461

Dr. Gustavo da Silva, André F. S. Luz, Denise Duarte, Dr. Diana Fontinha, Dr. Vera L. M. Silva, Dr. Filipe A. Almeida Paz, Dr. Ana M. Madureira, Dr. Sandra Sim?es, Dr. Miguel Prudêncio, Dr. Fátima Nogueira, Prof. Artur M. S. Silva, Prof. Rui Moreira

{"title":"Front Cover: Facile Access to Structurally Diverse Antimalarial Indoles Using a One-Pot A3 Coupling and Domino Cyclization Approach (ChemMedChem 17/2023)","authors":"Dr. Gustavo da Silva, André F. S. Luz, Denise Duarte, Dr. Diana Fontinha, Dr. Vera L. M. Silva, Dr. Filipe A. Almeida Paz, Dr. Ana M. Madureira, Dr. Sandra Sim?es, Dr. Miguel Prudêncio, Dr. Fátima Nogueira, Prof. Artur M. S. Silva, Prof. Rui Moreira","doi":"10.1002/cmdc.202300461","DOIUrl":"https://doi.org/10.1002/cmdc.202300461","url":null,"abstract":"The Front Cover depicts a female Anopheles spp. mosquito, the vector of Plasmodium falciparum and perhaps the most iconic image associated with the fight against malaria, which inspects the structure of a new indole scaffold with promising activity against blood-stage malaria parasites, under the moonlight (the vector has a nocturnal feeding habit, where transmission occurs). The highlighted lead compound is rising to the moon and above blood-stage parasitic forms of P. falciparum, in which this new scaffold revealed preferential inhibitory activity. The copyrighted Anopheles picture is used with the permission of Prof. Laurence J. Zwiebel. Cover design by Natália Marques Mota. More information can be found in the Research Article by Gustavo da Silva, Rui Moreira et al.<figure>\u0000 <div><picture>\u0000 <source></source></picture>\u0000 </div>\u0000 </figure>\u0000 ","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"18 17","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202300461","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6049977","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

Front Cover: A Study of the Activity of Adamantyl Amines against Mutant Influenza A M2 Channels Identified a Polycyclic Cage Amine Triple Blocker, Explored by Molecular Dynamics Simulations and Solid-State NMR (ChemMedChem 16/2023) 封面:金刚烷胺对突变型流感A M2通道的活性研究，鉴定了一个多环笼胺三重阻断剂，通过分子动力学模拟和固态核磁共振探索(ChemMedChem 16/2023)

IF 3.4 4区医学

ChemMedChem Pub Date : 2023-08-17 DOI: 10.1002/cmdc.202300429

Μarianna Stampolaki, Anja Hoffmann, Dr. Kumar Tekwani, Kyriakos Georgiou, Dr. Christina Tzitzoglaki, Dr. Chunlong Ma, Dr. Stefan Becker, Patrick Schmerer, Kristin D?ring, Dr. Ioannis Stylianakis, Dr. Andreea L. Turcu, Prof.?Dr. Jun Wang, Prof.?Dr. Santiago Vázquez, Prof.?Dr. Loren B. Andreas, Prof.?Dr. Michaela Schmidtke, Prof.?Dr. Antonios Kolocouris

{"title":"Front Cover: A Study of the Activity of Adamantyl Amines against Mutant Influenza A M2 Channels Identified a Polycyclic Cage Amine Triple Blocker, Explored by Molecular Dynamics Simulations and Solid-State NMR (ChemMedChem 16/2023)","authors":"Μarianna Stampolaki, Anja Hoffmann, Dr. Kumar Tekwani, Kyriakos Georgiou, Dr. Christina Tzitzoglaki, Dr. Chunlong Ma, Dr. Stefan Becker, Patrick Schmerer, Kristin D?ring, Dr. Ioannis Stylianakis, Dr. Andreea L. Turcu, Prof.?Dr. Jun Wang, Prof.?Dr. Santiago Vázquez, Prof.?Dr. Loren B. Andreas, Prof.?Dr. Michaela Schmidtke, Prof.?Dr. Antonios Kolocouris","doi":"10.1002/cmdc.202300429","DOIUrl":"https://doi.org/10.1002/cmdc.202300429","url":null,"abstract":"The Front Cover illustrates the L26F variant of the M2 protein of influenza A virus which is resistant to the amantadine class of drugs. It shows the combination of two methods (MD simulations and MAS NMR) that reveal the binding of a potent inhibitor of the L26F M2 proton channel, RL208, or compound 61 in the corresponding research. The ligand RL208 is an isomer of amantadine and is described as a triple blocker of WT, L26F, V27A M2 variants. Cover design by Marianna Stampolaki and Kyriakos Georgiou; image Virus Bacterium Infection by PublicDomainPictures from Pixabay used in accordance with the Pixabay license. More information can be found in the Research Article by Μarianna Stampolaki, Anja Hoffmann, Loren B. Andreas, Michaela Schmidtke, Antonios Kolocouris et al.<figure>\u0000 <div><picture>\u0000 <source></source></picture>\u0000 </div>\u0000 </figure>\u0000 ","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"18 16","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202300429","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5695847","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

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