ChemMedChem最新文献_第2页

5-Substituted Uridines with Activity against Gram-Positive Bacteria 具有抗革兰氏阳性菌活性的5-取代尿苷

IF 3.4 4区医学

ChemMedChem Pub Date : 2023-09-14 DOI: 10.1002/cmdc.202300366

Dmitry A. Makarov, Dr. Sergey D. Negrya, Maxim V. Jasko, Dr. Inna L. Karpenko, Dr. Pavel N. Solyev, Dr. Vladimir O. Chekhov, Dr. Dmitry N. Kaluzhny, Dr. Olga V. Efremenkova, Byazilya F. Vasilyeva, Dr. Alexander O. Chizhov, Dr. Darya A. Avdanina, Dr. Alexander A. Zhgun, Prof. Sergey N. Kochetkov, Dr. Liudmila A. Alexandrova

引用次数: 0

Development and Crosslinking Properties of Psoralen-Conjugated Triplex-Forming Oligonucleotides as Antigene Tools Targeting Genome DNA 作为靶向基因组DNA抗原工具的补骨脂素偶联三聚体寡核苷酸的开发及其交联特性

IF 3.4 4区医学

ChemMedChem Pub Date : 2023-09-13 DOI: 10.1002/cmdc.202300348

Dr. Yu Mikame, Honoka Eshima, Haruki Toyama, Juki Nakao, Misaki Matsuo, Dr. Tsuyoshi Yamamoto, Prof. Yoshiyuki Hari, Prof. Jun A. Komano, Prof. Asako Yamayoshi

{"title":"Development and Crosslinking Properties of Psoralen-Conjugated Triplex-Forming Oligonucleotides as Antigene Tools Targeting Genome DNA","authors":"Dr. Yu Mikame, Honoka Eshima, Haruki Toyama, Juki Nakao, Misaki Matsuo, Dr. Tsuyoshi Yamamoto, Prof. Yoshiyuki Hari, Prof. Jun A. Komano, Prof. Asako Yamayoshi","doi":"10.1002/cmdc.202300348","DOIUrl":"10.1002/cmdc.202300348","url":null,"abstract":"Psoralen-conjugated triplex-forming oligonucleotides (Ps-TFOs) have been utilized for genome editing and anti-gene experiments for over thirty years. However, the research on Ps-TFOs employing artificial nucleotides is still limited, and their photo-crosslinking properties have not been thoroughly investigated in relation to biological activities. In this study, we extensively examined the photo-crosslinking properties of Ps-TFOs to provide fundamental insights for future Ps-TFO design. We developed novel Ps-TFOs containing 2′-O,4′-C-methylene-bridged nucleic acids (Ps-LNA-mixmer) and investigated their photo-crosslinking properties using stable cell lines that express firefly luciferase constitutively to evaluate the anti-gene activities of Ps-LNA-mixmer. As a result, Ps-LNA-mixmer successfully demonstrated suppression activity, and we presented the first-ever correlation between photo-crosslinking properties and their activities. Our findings also indicate that the photo-crosslinking process is insufficient under cell irradiation conditions (365 nm, 2 mW/cm2, 60 min). Therefore, our results highlight the need to develop new psoralen derivatives that are more reactive under cell irradiation conditions.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"18 21","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10229467","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: 1

Design, Synthesis of (±)-Millpuline A, and Biological Evaluation for the Lung Cell Protective Effects through SRC （±）-Millpuline的设计、合成 A、以及通过SRC对肺细胞保护作用的生物学评价。

IF 3.4 4区医学

ChemMedChem Pub Date : 2023-09-13 DOI: 10.1002/cmdc.202300219

Heng Zhang, Xiao Guo, Di Zhou, Jiatong Wen, Yingzhan Tang, Jian Wang, Prof. Dr. Yang Liu, Prof. Dr. Gang Chen, Prof. Dr. Ning Li

{"title":"Design, Synthesis of (±)-Millpuline A, and Biological Evaluation for the Lung Cell Protective Effects through SRC","authors":"Heng Zhang, Xiao Guo, Di Zhou, Jiatong Wen, Yingzhan Tang, Jian Wang, Prof. Dr. Yang Liu, Prof. Dr. Gang Chen, Prof. Dr. Ning Li","doi":"10.1002/cmdc.202300219","DOIUrl":"10.1002/cmdc.202300219","url":null,"abstract":"In this study, a visible-light-induced intermolecular [2+2] photocycloaddition reaction based on flavonoids was constructed to address the problems of low yield, poor physicochemical properties, and lack of target definition in total synthesis of (±)-millpuline A whose bioactivity remains unknown. As a result, 20 derivatives were synthesized for bioactivity evaluation. Consequently, lung cell protective effects of (±)-millpuline A and compound B13 a were revealed for the first time and the crucial role of stereoconfiguration of the cyclobutane moiety in their protective effects against NNK in normal lung cells was demonstrated. Moreover, through target prediction and experimental verification in MLE-12 cells, SRC was determined to be the target of (±)-millpuline A regarding its protective effect in NNK-induced lung cell injury. Results from RT-Q-PCR and HTRF experiments verified that (±)-millpuline A could repress SRC activity through a transcriptional mechanism but not acting as an inhibitor to directly bind to and thereby inhibit SRC protein. The results in this paper are informative for the further development of visible light-catalyzed cycloaddition of flavonoids and lay a scientific foundation for understanding the bioactivity and underlying mechanism of (±)-millpuline A and other structurally similar natural skeletons.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"18 20","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10234936","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

Structural Modification of the Natural Product Valerenic Acid Tunes RXR Homodimer Agonism 天然产物戊酸的结构修饰可调节RXR同型二聚体的激动作用

IF 3.4 4区医学

ChemMedChem Pub Date : 2023-09-12 DOI: 10.1002/cmdc.202300404

Daniel Zaienne, Laura Isigkeit, Dr. Julian A. Marschner, Silke Duensing-Kropp, Dr. Georg Höfner, Prof. Dr. Daniel Merk

引用次数: 1

Antimalarial Agents Targeting Plasmodium falciparum Carbonic Anhydrase: Towards Artesunate Hybrid Compounds with Dual Mechanism of Action 以恶性疟原虫碳酸酐酶为靶点的抗疟药物:面向具有双重作用机制的青蒿琥酯杂化化合物

IF 3.4 4区医学

ChemMedChem Pub Date : 2023-09-12 DOI: 10.1002/cmdc.202300267

Dr. Ilaria D'Agostino, Prof. Susi Zara, Prof. Simone Carradori, Dr. Viviana De Luca, Dr. Clemente Capasso, Dr. Clemens H. M. Kocken, Dr. Anne-Marie Zeeman, Dr. Andrea Angeli, Prof. Fabrizio Carta, Prof. Claudiu T. Supuran

{"title":"Antimalarial Agents Targeting Plasmodium falciparum Carbonic Anhydrase: Towards Artesunate Hybrid Compounds with Dual Mechanism of Action","authors":"Dr. Ilaria D'Agostino, Prof. Susi Zara, Prof. Simone Carradori, Dr. Viviana De Luca, Dr. Clemente Capasso, Dr. Clemens H. M. Kocken, Dr. Anne-Marie Zeeman, Dr. Andrea Angeli, Prof. Fabrizio Carta, Prof. Claudiu T. Supuran","doi":"10.1002/cmdc.202300267","DOIUrl":"10.1002/cmdc.202300267","url":null,"abstract":"Malaria continues to be a major public health challenge worldwide and, as part of the global effort toward malaria eradication, plasmodium carbonic anhydrases (CAs) have recently been proposed as potential targets for malaria treatment. In this study, a series of eight hybrid compounds combining the Artesunate core with a sulfonamide moiety were synthesized and evaluated for their inhibition potency against the widely expressed human (h) CAs I, II and the isoform from P. falciparum (PfCA). All derivatives demonstrated high inhibition potency against PfCA, achieving a KI value in the sub-nanomolar range (0.35 nM). Two Compounds showed a selectivity index of 4.1 and 3.1, respectively, against this protozoan isoform compared to hCA II. Three Derivatives showed no cytotoxic effects on human gingival fibroblasts at 50 μM with a high killing rate against both P. falciparum and P. knowlesi strains with IC50 in the sub-nanomolar range, providing a wide therapeutic window. Our findings suggest that these compounds may serve as promising leads for developing new antimalarial drugs and warrant further investigation, including activity against antimalarial-resistant strains, mode of action studies, and in vivo efficacy assessment in preclinical mouse models of malaria.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"18 21","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10268327","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

Screening Campaign and Docking Investigations in Identifying New Hit Compounds as Inhibitors of Human Carbonic Anhydrases Expressed In Tumour Cells 鉴定新的Hit化合物作为肿瘤细胞中表达的人碳酸酐酶抑制剂的筛选活动和对接研究。

IF 3.4 4区医学

ChemMedChem Pub Date : 2023-09-11 DOI: 10.1002/cmdc.202300330

Federico Ricci, Dr. Andrea Angeli, Dr. Francesca Mancuso, Prof. Laura De Luca, Prof. Claudiu T. Supuran, Prof. Rosaria Gitto

{"title":"Screening Campaign and Docking Investigations in Identifying New Hit Compounds as Inhibitors of Human Carbonic Anhydrases Expressed In Tumour Cells","authors":"Federico Ricci, Dr. Andrea Angeli, Dr. Francesca Mancuso, Prof. Laura De Luca, Prof. Claudiu T. Supuran, Prof. Rosaria Gitto","doi":"10.1002/cmdc.202300330","DOIUrl":"10.1002/cmdc.202300330","url":null,"abstract":"The tumor-expressed human carbonic anhydrase (hCA) isoforms hCA IX and hCA XII have been extensively studied to develop anticancer agents targeting solid tumors in combined therapy. These CA isoforms are considered key factors in controlling tumor microenvironment (TME) of cancer lines that develop high metastatic activity. Herein, we report the discovery of potent hCA IX/hCA XII inhibitors that were disclosed through a screening campaign on an in-house collection of arylsulfonamides preliminary tested toward other hCAs. Among them, the N-(4-sulfamoylphenyl)naphthalene-2-carboxamide (12) and N-(4-sulfamoylphenyl)-3,4-dihydroisoquinoline-2(1H)-carbothioamide (15) proved to be the most intriguing hCA IX/hCA XII inhibitors displaying favourable selectivity ratios over widespread hCA I and hCA II isoforms. To explore their binding mode, we conducted docking studies that described the poses of the best inhibitors in the catalytic site of hCA IX and hCA XII, thus suggesting the privileged pattern of interactions. These structural findings might further improve the knowledge for a successful identification of new sulfonamides as adjuvant agents in cancer management.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"18 20","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10205973","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

[1,2,4]Triazolo[1,5-c]pyrimidines as Tools to Investigate A3 Adenosine Receptors in Cancer Cell Lines [1,2,4]三唑[1,5-c]嘧啶类化合物在肿瘤细胞A3腺苷受体研究中的应用

IF 3.4 4区医学

ChemMedChem Pub Date : 2023-09-07 DOI: 10.1002/cmdc.202300299

Prof. Stephanie Federico, Margherita Persico, Letizia Trevisan, Chiara Biasinutto, Dr. Giovanni Bolcato, Dr. Veronica Salmaso, Prof. Tatiana Da Ros, Dr. Teresa Gianferrara, Dr. Filippo Prencipe, Sonja Kachler, Prof. Karl-Norbert Klotz, Prof. Sabrina Pacor, Prof. Stefano Moro, Prof. Giampiero Spalluto

{"title":"[1,2,4]Triazolo[1,5-c]pyrimidines as Tools to Investigate A3 Adenosine Receptors in Cancer Cell Lines","authors":"Prof. Stephanie Federico, Margherita Persico, Letizia Trevisan, Chiara Biasinutto, Dr. Giovanni Bolcato, Dr. Veronica Salmaso, Prof. Tatiana Da Ros, Dr. Teresa Gianferrara, Dr. Filippo Prencipe, Sonja Kachler, Prof. Karl-Norbert Klotz, Prof. Sabrina Pacor, Prof. Stefano Moro, Prof. Giampiero Spalluto","doi":"10.1002/cmdc.202300299","DOIUrl":"10.1002/cmdc.202300299","url":null,"abstract":"The A3 adenosine receptor is an interesting target whose role in cancer is controversial. In this work, a structural investigation at the 2-position of the [1,2,4]triazolo[1,5-c]pyrimidine nucleus was performed, finding new potent and selective A3 adenosine receptor antagonists such as the ethyl 2-(4-methoxyphenyl)-5-(methylamino)-[1,2,4]triazolo[1,5-c]pyrimidine-8-carboxylate (20, DZ123) that showed a Ki value of 0.47 nM and an exceptional selectivity profile over the other adenosine receptor subtypes. Computational studies were performed to rationalize the affinity and the selectivity profile of the tested compounds at the A3 adenosine receptor and the A1 and A2A adenosine receptors. Compound 20 was tested on both A3 adenosine receptor positive cell lines (CHO-A3AR transfected, THP1 and HCT16) and on A3 negative cancer cell lines, showing no effect in the latter and a pro-proliferative effect at a low concentration in the former. These interesting results pave the way to further investigation on both the mechanism involved and potential therapeutic applications.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":"18 21","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10171303","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

Zwitterionic Polymer: A New Paradigm for Protein Conjugation beyond PEG 两性离子聚合物：超越PEG的蛋白质偶联新范式。

IF 3.4 4区医学

ChemMedChem Pub Date : 2023-09-07 DOI: 10.1002/cmdc.202300245

Dr. Zhipeng Zeng, Shi Chen, Prof. Yongming Chen

引用次数: 0

Corrigendum: 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 更正：一项关于金刚烷胺对突变型甲型流感M2通道活性的研究确定了一种多环笼胺三阻断剂，通过分子动力学模拟和固态NMR进行了探索。

IF 3.4 4区医学

ChemMedChem Pub Date : 2023-09-04 DOI: 10.1002/cmdc.202300455

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