Journal of Enzyme Inhibition and Medicinal Chemistry最新文献_第9页

The activity of pyrazolo[4,3-e][1,2,4]triazine and pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulphonamide derivatives in monolayer and spheroid breast cancer cell cultures. 吡唑并[4,3-e][1,2,4]三嗪和吡唑并[4,3-e]四唑并[1,5-b][1,2,4]三嗪磺酰胺衍生物在单层和球形乳腺癌细胞培养中的活性。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-05-03 DOI: 10.1080/14756366.2024.2343352

Anna Szymanowska, Dominika Radomska, Robert Czarnomysy, Mariusz Mojzych, Katarzyna Kotwica-Mojzych, Krzysztof Bielawski, Anna Bielawska

{"title":"The activity of pyrazolo[4,3-e][1,2,4]triazine and pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulphonamide derivatives in monolayer and spheroid breast cancer cell cultures.","authors":"Anna Szymanowska, Dominika Radomska, Robert Czarnomysy, Mariusz Mojzych, Katarzyna Kotwica-Mojzych, Krzysztof Bielawski, Anna Bielawska","doi":"10.1080/14756366.2024.2343352","DOIUrl":"10.1080/14756366.2024.2343352","url":null,"abstract":"In the last decade, an increasing interest in compounds containing pyrazolo[4,3-e][1,2,4]triazine moiety is observed. Therefore, the aim of the research was to synthesise a novel sulphonyl pyrazolo[4,3-e][1,2,4]triazines (2a, 2b) and pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulphonamide derivatives (3a, 3b) to assess their anticancer activity. The MTT assay showed that 2a, 2b, 3a, 3b have stronger cytotoxic activity than cisplatin in both breast cancer cells (MCF-7 and MDA-MB-231) and exhibited weaker effect on normal breast cells (MCF-10A). The obtained results showed that the most active compound 3b increased apoptosis via caspase 9, caspase 8, and caspase 3/7. It is worth to note that compound 3b suppressed NF-κB expression and promoted p53, Bax, and ROS which play important role in activation of apoptosis. Moreover, our results confirmed that compound 3b triggers autophagy through increased formation of autophagosomes, expression of beclin-1 and mTOR inhibition. Thus, our study defines a possible mechanism underlying 3b-induced anti-cancer activity against breast cancer cell lines.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2343352"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11073428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Searching for novel MDM2/MDMX dual inhibitors through a drug repurposing approach. 通过药物再利用方法寻找新的MDM2/MDMX双重抑制剂。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2023-12-07 DOI: 10.1080/14756366.2023.2288810

Keting Li, Wenshu Hu, Yingjie Wang, Wenxing Chen, Hongmei Wen, Jian Liu, Wei Li, Bo Wang

{"title":"Searching for novel MDM2/MDMX dual inhibitors through a drug repurposing approach.","authors":"Keting Li, Wenshu Hu, Yingjie Wang, Wenxing Chen, Hongmei Wen, Jian Liu, Wei Li, Bo Wang","doi":"10.1080/14756366.2023.2288810","DOIUrl":"10.1080/14756366.2023.2288810","url":null,"abstract":"Disruption of p53-MDM2/MDMX interaction by smaller inhibitors is a promising therapeutic intervention gaining tremendous interest. However, no MDM2/MDMX inhibitors have been marketed so far. Drug repurposing is a validated, practical approach to drug discovery. In this regard, we employed structure-based virtual screening in a reservoir of marketed drugs and identified nintedanib as a new MDM2/MDMX dual inhibitor. The computational structure analysis and biochemical experiments uncover that nintedanib binds MDM2/MDMX similarly to RO2443, a dual MDM2/MDMX inhibitor. Furthermore, the mechanistic study reveals that nintedanib disrupts the physical interaction of p53-MDM2/MDMX, enabling the transcriptional activation of p53 and the subsequent cell cycle arrest and growth inhibition in p53+/+ cancer cells. Lastly, structural minimisation of nintedanib yields H3 with the equivalent potency. In summary, this work provides a solid foundation for reshaping nintedanib as a valuable lead compound for the further design of MDM2/MDMX dual inhibitors.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2288810"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Suppression of lipopolysaccharide-induced COX-2 expression via p38MAPK, JNK, and C/EBPβ phosphorylation inhibition by furomagydarin A, a benzofuran glycoside from Magydaris pastinacea. 马尾黄苷A(一种来自马尾黄的苯并呋喃苷)通过抑制p38MAPK、JNK和C/EBPβ磷酸化抑制脂多糖诱导的COX-2表达

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2023-12-07 DOI: 10.1080/14756366.2023.2287420

Shiu-Wen Huang, Ming Jen Hsu, Hsiu-Chen Chen, Rita Meleddu, Simona Distinto, Elias Maccioni, Filippo Cottiglia

引用次数: 0

Novel alloxazine analogues: design, synthesis, and antitumour efficacy enhanced by kinase screening, molecular docking, and ADME studies. 新型烯丙基嗪类似物：通过激酶筛选、分子对接和 ADME 研究提高设计、合成和抗肿瘤功效。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-09-17 DOI: 10.1080/14756366.2024.2398551

Doaa Samaha,Sawsan Mahmoud,Mosaad Sayed Mohamed,Rokaia S Abdullah,Nageh A Abou Taleb,Tomohisa Nagamatsu,Hamed I Ali

{"title":"Novel alloxazine analogues: design, synthesis, and antitumour efficacy enhanced by kinase screening, molecular docking, and ADME studies.","authors":"Doaa Samaha,Sawsan Mahmoud,Mosaad Sayed Mohamed,Rokaia S Abdullah,Nageh A Abou Taleb,Tomohisa Nagamatsu,Hamed I Ali","doi":"10.1080/14756366.2024.2398551","DOIUrl":"https://doi.org/10.1080/14756366.2024.2398551","url":null,"abstract":"This study describes the development of novel alloxazine analogues as potent antitumor agents with enhanced selectivity for tumour cells. Twenty-nine out of 45 newly compounds were investigated in vitro for their growth inhibitory activities, against two human tumour cell lines, namely, the human T-cell acute lymphoblastoid leukaemia cell line (CCRF-HSB-2) and human oral epidermoid carcinoma cell line (KB), and the antitumor agent \"Ara-C\" was used as a positive reference in this investigation. Compounds 9e and 10J were the highest among their analogues, against both tumour cell lines (CCRF-HSB-2 and KB). Correlation analyses demonstrated a strong relationship between the IC50 values and AutoDock binding free energy or calculated inhibition (Ki). The study delves into structure-activity relationships (SARs) through advanced modelling tools integrated with structure-based drug design (SBDD) using GOLD 5.2.2, AutoDock 4.2, and Accelrys Discovery Studio 3.5. Physicochemical properties, pharmacokinetics, drug-likeness, and toxicity predictions of the most potent alloxazine derivatives were conducted using ProTox-II and Swiss ADME for effective antitumor agents with improved selectivity.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"23 1","pages":"2398551"},"PeriodicalIF":5.6,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Challenging the Biginelli scaffold to surpass the first line antitubercular drugs: Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt) inhibition activity and molecular modelling studies 挑战 Biginelli 支架，超越一线抗结核药物：结核分枝杆菌胸苷单磷酸激酶（TMPKmt）抑制活性和分子模型研究

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-09-11 DOI: 10.1080/14756366.2024.2386668

Mai S. El-Shoukrofy, Amal Atta, Salwa Fahmy, Dharmarajan Sriram, Michael G. Shehat, Ibrahim M. Labouta, Mona A. Mahran

引用次数: 0

Synthesis and in vitro evaluation of benzo[b]thiophene-3-carboxylic acid 1,1-dioxide derivatives as anticancer agents targeting the RhoA/ROCK pathway. 苯并[b]噻吩-3-羧酸 1,1-二氧化物衍生物作为靶向 RhoA/ROCK 通路的抗癌剂的合成和体外评估。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-09-11 DOI: 10.1080/14756366.2024.2390911

Jinhao Liang,Jin Huang,Jianzhan Yang,Weihong Liang,Haoxiang Li,Yunshan Wu,Bo Liu

{"title":"Synthesis and in vitro evaluation of benzo[b]thiophene-3-carboxylic acid 1,1-dioxide derivatives as anticancer agents targeting the RhoA/ROCK pathway.","authors":"Jinhao Liang,Jin Huang,Jianzhan Yang,Weihong Liang,Haoxiang Li,Yunshan Wu,Bo Liu","doi":"10.1080/14756366.2024.2390911","DOIUrl":"https://doi.org/10.1080/14756366.2024.2390911","url":null,"abstract":"Rho family GTPases regulate cellular processes and promote tumour growth and metastasis; thus, RhoA is a potential target for tumour metastasis inhibition. However, limited progress has been made in the development of RhoA targeting anticancer drugs. Here, we synthesised benzo[b]thiophene-3-carboxylic acid 1,1-dioxide derivatives based on a covalent inhibitor of RhoA (DC-Rhoin), reported in our previous studies. The observed structure-activity relationship (contributed by carboxamide in C-3 and 1-methyl-1H-pyrazol in C-5) enhanced the anti-proliferative activity of the derivatives. Compound b19 significantly inhibited the proliferation, migration, and invasion of MDA-MB-231 cells and promoted their apoptosis. The suppression of myosin light chain phosphorylation and the formation of stress fibres confirmed the inhibitory activity of b19 via the RhoA/ROCK pathway. b19 exhibited a different binding pattern from DC-Rhoin, as observed in molecular docking analysis. This study provides a reference for the development of anticancer agents targeting the RhoA/ROCK pathway.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"26 1","pages":"2390911"},"PeriodicalIF":5.6,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142221560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Discovery of novel FGFR4 inhibitors through a build-up fragment strategy 通过积累片段策略发现新型表皮生长因子受体 4 抑制剂

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-04-24 DOI: 10.1080/14756366.2024.2343350

Jihyung Kim, Chang Gyun Im, Kyujin Oh, Ji Min Lee, Fatimah Al-Rubaye, K. Min

引用次数: 0

Targeting bacterial growth in biofilm conditions: rational design of novel inhibitors to mitigate clinical and food contamination using QSAR 针对生物膜条件下的细菌生长：利用 QSAR 合理设计新型抑制剂，减轻临床和食品污染

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-04-23 DOI: 10.1080/14756366.2024.2330907

Maria Galvez-Llompart, Jesús Hierrezuelo, Mariluz Blasco, Riccardo Zanni, Jorge Galvez, A. de Vicente, A. Pérez-García, D. Romero

引用次数: 0

Evaluation of the anticancer effects exerted by 5-fluorouracil and heme oxygenase-1 inhibitor hybrids in HTC116 colorectal cancer cells 评估 5-氟尿嘧啶和血红素加氧酶-1 抑制剂混合物在 HTC116 大肠癌细胞中发挥的抗癌作用

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-04-18 DOI: 10.1080/14756366.2024.2337191

Loredana Salerno, Antonietta Notaro, Valeria Consoli, Federica Affranchi, Valeria Pittalà, Valeria Sorrenti, Luca Vanella, Michela Giuliano, Sebastiano Intagliata

引用次数: 0

Synthesis, carbonic anhydrase inhibition studies and modelling investigations of phthalimide–hydantoin hybrids 邻苯二甲酰亚胺-海因杂化物的合成、碳酸酐酶抑制研究和模型研究

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-04-12 DOI: 10.1080/14756366.2024.2335927

Morteza Abdoli, Alessandro Bonardi, Paola Gratteri, Claudiu T. Supuran, Raivis Žalubovskis

引用次数: 0