Journal of Enzyme Inhibition and Medicinal Chemistry最新文献_第10页

Ligand-based pharmacophore modelling, structure optimisation, and biological evaluation for the identification of 2-heteroarylthio-N-arylacetamides as novel HSP90 C-terminal inhibitors 基于配体的药效学建模、结构优化和生物学评价，鉴定作为新型 HSP90 C 端抑制剂的 2-heteroarylthio-N-arylacetamides

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2023-12-11 DOI: 10.1080/14756366.2023.2290912

Yajun Liu, Chenyao Li, Yajing Li, Shuming Zhang, Ning Zhang, Xiaobo Bian, Shutao Tan

引用次数: 0

Novel tetrahydronaphthalen-1-yl-phenethyl ureas: synthesis and dual antibacterial-anticancer activities 新型四氢萘-1-基-苯乙基脲：合成与双重抗菌抗癌活性

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2023-12-07 DOI: 10.1080/14756366.2023.2286925

Yusuf Akbaba, Fatma Necmiye Kacı, Mehmet Enes Arslan, Süleyman Göksü, Adil Mardinoğlu, Hasan Türkez

引用次数: 0

Design and synthesis of doublecortin-like kinase 1 inhibitors and their bioactivity evaluation 双皮质素样激酶 1 抑制剂的设计、合成及其生物活性评估

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2023-12-07 DOI: 10.1080/14756366.2023.2287990

Pengming Pan, Dengbo Ji, Zhongjun Li, Xiangbao Meng

引用次数: 0

Novel harmine derivatives as potent acetylcholinesterase and amyloid beta aggregation dual inhibitors for management of Alzheimer's disease. 新的毒蜂碱衍生物作为有效的乙酰胆碱酯酶和β淀粉样蛋白聚集双重抑制剂用于阿尔茨海默病的治疗。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2023-12-01 Epub Date: 2023-11-15 DOI: 10.1080/14756366.2023.2281893

Hongtao Du, Jinzhi Song, Fang Ma, Hongxin Gao, Xinyan Zhao, Renjun Mao, Xiaolong He, Yan Yan

{"title":"Novel harmine derivatives as potent acetylcholinesterase and amyloid beta aggregation dual inhibitors for management of Alzheimer's disease.","authors":"Hongtao Du, Jinzhi Song, Fang Ma, Hongxin Gao, Xinyan Zhao, Renjun Mao, Xiaolong He, Yan Yan","doi":"10.1080/14756366.2023.2281893","DOIUrl":"10.1080/14756366.2023.2281893","url":null,"abstract":"In this study, a series of potential ligands for the treatment of AD were synthesised and characterised as novel harmine derivatives modified at position 9 with benzyl piperazinyl. In vitro studies revealed that the majority of the derivatives exhibited moderate to potent inhibition against hAChE and Aβ1 - 42 aggregation. Notably, compounds 13 and 17d displayed potent drug - likeness and ADMET properties, demonstrating remarkable inhibitory activities towards AChE (IC50 = 58.76 nM and 89.38 nM, respectively) as well as Aβ aggregation (IC50 = 9.31 μM and 13.82 μM, respectively). More importantly, compounds 13 and 17d showed exceptional neuroprotective effects against Aβ1 - 42-induced SH - SY5Y damage, while maintaining low toxicity in SH - SY5Y cells. Further exploration of the mechanism through kinetic studies and molecular modelling confirmed that compound 13 could interact with both the CAS and the PAS of AChE. These findings suggested that harmine derivatives hold great potential as dual - targeted candidates for treating AD.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10653770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107591366","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

Selected strategies to fight pathogenic bacteria. 对抗致病菌的精选策略。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2023-12-01 DOI: 10.1080/14756366.2022.2155816

Aiva Plotniece, Arkadij Sobolev, Claudiu T Supuran, Fabrizio Carta, Fredrik Björkling, Henrik Franzyk, Jari Yli-Kauhaluoma, Koen Augustyns, Paul Cos, Linda De Vooght, Matthias Govaerts, Juliana Aizawa, Päivi Tammela, Raivis Žalubovskis

{"title":"Selected strategies to fight pathogenic bacteria.","authors":"Aiva Plotniece, Arkadij Sobolev, Claudiu T Supuran, Fabrizio Carta, Fredrik Björkling, Henrik Franzyk, Jari Yli-Kauhaluoma, Koen Augustyns, Paul Cos, Linda De Vooght, Matthias Govaerts, Juliana Aizawa, Päivi Tammela, Raivis Žalubovskis","doi":"10.1080/14756366.2022.2155816","DOIUrl":"10.1080/14756366.2022.2155816","url":null,"abstract":"Natural products and analogues are a source of antibacterial drug discovery. Considering drug resistance levels emerging for antibiotics, identification of bacterial metalloenzymes and the synthesis of selective inhibitors are interesting for antibacterial agent development. Peptide nucleic acids are attractive antisense and antigene agents representing a novel strategy to target pathogens due to their unique mechanism of action. Antisense inhibition and development of antisense peptide nucleic acids is a new approach to antibacterial agents. Due to the increased resistance of biofilms to antibiotics, alternative therapeutic options are necessary. To develop antimicrobial strategies, optimised in vitro and in vivo models are needed. In vivo models to study biofilm-related respiratory infections, device-related infections: ventilator-associated pneumonia, tissue-related infections: chronic infection models based on alginate or agar beads, methods to battle biofilm-related infections are discussed. Drug delivery in case of antibacterials often is a serious issue therefore this review includes overview of drug delivery nanosystems.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9848314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10554656","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

Design, synthesis and biological evaluation of 2-((4-sulfamoylphenyl)amino)-pyrrolo[2,3-d]pyrimidine derivatives as CDK inhibitors. 2-((4-磺胺基苯基)氨基吡咯[2,3-d]嘧啶衍生物CDK抑制剂的设计、合成及生物学评价。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2023-12-01 DOI: 10.1080/14756366.2023.2169282

Bo Yang, Yanni Quan, Wuli Zhao, Yingjie Ji, Xiaotang Yang, Jianrui Li, Yi Li, Xiujun Liu, Ying Wang, Yanping Li

{"title":"Design, synthesis and biological evaluation of 2-((4-sulfamoylphenyl)amino)-pyrrolo[2,3-d]pyrimidine derivatives as CDK inhibitors.","authors":"Bo Yang, Yanni Quan, Wuli Zhao, Yingjie Ji, Xiaotang Yang, Jianrui Li, Yi Li, Xiujun Liu, Ying Wang, Yanping Li","doi":"10.1080/14756366.2023.2169282","DOIUrl":"10.1080/14756366.2023.2169282","url":null,"abstract":"To explore the potential use of CDK inhibitors in pancreatic ductal adenocarcinoma (PDAC) therapy, a series of novel 2-((4-sulfamoylphenyl)amino)-pyrrolo[2,3-d]pyrimidine derivatives was designed, synthesised, and investigated for inhibition on both CDK kinase activity and cellular proliferation of pancreatic cancer. Most of new sulphonamide-containing derivatives demonstrated strong inhibitory activity on CDK9 and obvious anti-proliferative activity in cell culture. Moreover, two new compounds suppressed cell proliferation of multiple human pancreatic cancer cell lines. The most potent compound 2g inhibited cancer cell proliferation by blocking Rb phosphorylation and induced apoptosis via downregulation of CDK9 downstream proteins Mcl-1 and c-Myc in MIA PaCa-2 cells. CDK9 knockdown experiment suggests its anti-proliferative activity is mainly mediated by CDK9. Additionally, 2g displayed moderate tumour inhibition effect in AsPC-1 derived xenograft mice model. Altogether, this study provided a new start for further optimisation to develop potential CDK inhibitor candidates for PDAC treatment by alone or combination use.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9858427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9227638","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: 2

Oxidation of flavonoids by tyrosinase and by o-quinones-comment on "Flavonoids as tyrosinase inhibitors in in silico and in vitro models: basic framework of SAR using a statistical modelling approach" published by K. Jakimiuk, S. Sari, R. Milewski, C.T. Supuran, D. Şöhretoğlu, and M. Tomczyk (J Enzyme Inhib Med Chem 2022;37:427-436). 酪氨酸酶和邻醌对黄酮类化合物的氧化——对K.Jakimiuk、S.Sari、R.Milewski、C.T.Supuran、D.Şhretoğlu和M.Tomczyk发表的“计算机和体外模型中黄酮类化合物作为酪氨酸酶抑制剂：使用统计建模方法的SAR的基本框架”的评论（J Enzyme Inhib Med Chem 2022；37:427-436）。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2023-12-01 Epub Date: 2023-10-16 DOI: 10.1080/14756366.2023.2269611

Hubert Wojtasek

引用次数: 0

Latest advances in dual inhibitors of acetylcholinesterase and monoamine oxidase B against Alzheimer's disease. 乙酰胆碱酯酶和单胺氧化酶B双抑制剂抗阿尔茨海默病的最新进展。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2023-12-01 Epub Date: 2023-11-13 DOI: 10.1080/14756366.2023.2270781

Dajiang Zou, Renzheng Liu, Yangjing Lv, Jianan Guo, Changjun Zhang, Yuanyuan Xie

{"title":"Latest advances in dual inhibitors of acetylcholinesterase and monoamine oxidase B against Alzheimer's disease.","authors":"Dajiang Zou, Renzheng Liu, Yangjing Lv, Jianan Guo, Changjun Zhang, Yuanyuan Xie","doi":"10.1080/14756366.2023.2270781","DOIUrl":"10.1080/14756366.2023.2270781","url":null,"abstract":"Alzheimer's disease (AD) is a progressive brain disease characterised by progressive memory loss and cognition impairment, ultimately leading to death. There are three FDA-approved acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine, AChEIs) for the symptomatic treatment of AD. Monoamine oxidase B (MAO-B) has been considered to contribute to pathologies of AD. Therefore, we reviewed the dual inhibitors of acetylcholinesterase (AChE) and MAO-B developed in the last five years. In this review, these dual-target inhibitors were classified into six groups according to the basic parent structure, including chalcone, coumarin, chromone, benzo-fused five-membered ring, imine and hydrazine, and other scaffolds. Their design strategies, structure-activity relationships (SARs), and molecular docking studies with AChE and MAO-B were analysed and discussed, giving valuable insights for the subsequent development of AChE and MAO-B dual inhibitors. Challenges in the development of balanced and potent AChE and MAO-B dual inhibitors were noted, and corresponding solutions were provided.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10653629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89718537","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

New 1,2,3-triazole/1,2,4-triazole hybrids linked to oxime moiety as nitric oxide donor selective COX-2, aromatase, B-RAFV600E and EGFR inhibitors celecoxib analogs: design, synthesis, anti-inflammatory/anti-proliferative activities, apoptosis and molecular modeling study 作为一氧化氮供体的选择性 COX-2、芳香化酶、B-RAFV600E 和表皮生长因子受体抑制剂塞来昔布类似物：设计、合成、抗炎/抗增殖活性、细胞凋亡和分子模型研究

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2023-12-01 DOI: 10.1080/14756366.2023.2290461

Wael A. A. Fadaly, M. T. Nemr, Taha H. Zidan, Fatma E. A. Mohamed, Marwa M. Abdelhakeem, Nour N. Abu Jayab, Hany A. Omar, Khaled R. A. Abdellatif

{"title":"New 1,2,3-triazole/1,2,4-triazole hybrids linked to oxime moiety as nitric oxide donor selective COX-2, aromatase, B-RAFV600E and EGFR inhibitors celecoxib analogs: design, synthesis, anti-inflammatory/anti-proliferative activities, apoptosis and molecular modeling study","authors":"Wael A. A. Fadaly, M. T. Nemr, Taha H. Zidan, Fatma E. A. Mohamed, Marwa M. Abdelhakeem, Nour N. Abu Jayab, Hany A. Omar, Khaled R. A. Abdellatif","doi":"10.1080/14756366.2023.2290461","DOIUrl":"https://doi.org/10.1080/14756366.2023.2290461","url":null,"abstract":"Abstract A new series of bis-triazole 19a-l was synthesised for the purpose of being hybrid molecules with both anti-inflammatory and anti-cancer activities and assessed for cell cycle arrest, NO release. Compounds 19c, 19f, 19h, 19 l exhibited COX-2 selectivity indexes in the range of 18.48 to 49.38 compared to celecoxib S.I. = 21.10), inhibit MCF-7 with IC50 = 9–16 μM compared to tamoxifen (IC50 = 27.9 μM). and showed good inhibitory activity against HEP-3B with IC50 = 4.5–14 μM compared to sorafenib (IC50 = 3.5 μM) (HEP-3B). Moreover, derivatives 19e, 19j, 19k, 19 l inhibit HCT-116 with IC50 = 5.3–13.7 μM compared to 5-FU with IC50 = 4.8 μM (HCT-116). Compounds 19c, 19f, 19h, 19 l showed excellent inhibitory activity against A549 with IC50 = 3–4.5 μM compared to 5-FU with IC50 = 6 μM (A549). Compounds 19c, 19f, 19h, 19 l inhibit aromatase (IC50 of 22.40, 23.20, 22.70, 30.30 μM), EGFR (IC50 of 0.112, 0.205, 0.169 and 0.066 μM) and B-RAFV600E (IC50 of 0.09, 0.06, 0.07 and 0.05 μM).","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138612186","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

New pyrazolyl-thiazolidinone/thiazole derivatives as celecoxib/dasatinib analogues with selective COX-2, HER-2 and EGFR inhibitory effects: design, synthesis, anti-inflammatory/anti-proliferative activities, apoptosis, molecular modelling and ADME studies. 具有选择性COX-2、HER-2和EGFR抑制作用的新型吡唑基噻唑烷酮/噻唑衍生物塞来昔布/达沙替尼类似物:设计、合成、抗炎/抗增殖活性、细胞凋亡、分子模型和ADME研究

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2023-12-01 Epub Date: 2023-11-27 DOI: 10.1080/14756366.2023.2281262

Wael A A Fadaly, Taha H Zidan, Nesma M Kahk, Fatma E A Mohamed, Marwa M Abdelhakeem, Rehab G Khalil, Mohamed T M Nemr

{"title":"New pyrazolyl-thiazolidinone/thiazole derivatives as celecoxib/dasatinib analogues with selective COX-2, HER-2 and EGFR inhibitory effects: design, synthesis, anti-inflammatory/anti-proliferative activities, apoptosis, molecular modelling and ADME studies.","authors":"Wael A A Fadaly, Taha H Zidan, Nesma M Kahk, Fatma E A Mohamed, Marwa M Abdelhakeem, Rehab G Khalil, Mohamed T M Nemr","doi":"10.1080/14756366.2023.2281262","DOIUrl":"10.1080/14756366.2023.2281262","url":null,"abstract":"Two new series of pyrazolyl-thiazolidinone/thiazole derivatives 16a-b and 18a-j were synthesised, merging the scaffolds of celecoxib and dasatinib. Compounds 16a, 16b and 18f inhibit COX-2 with S.I. 134.6, 26.08 and 42.13 respectively (celecoxib S.I. = 24.09). Compounds 16a, 16b, 18c, 18d and 18f inhibit MCF-7 with IC50 = 0.73-6.25 μM (dasatinib IC50 = 7.99 μM) and (doxorubicin IC50 = 3.1 μM) and inhibit A549 with IC50 = 1.64-14.3 μM (dasatinib IC50 = 11.8 μM and doxorubicin IC50 = 2.42 μM) with S.I. (F180/MCF7) of 33.15, 7.13, 18.72, 13.25 and 8.28 respectively higher than dasatinib (4.03) and doxorubicin (3.02) and S.I. (F180/A549) of 14.75, 12.96, 4.16, 7.07 and 18.88 respectively higher than that of dasatinib (S.I. = 2.72) and doxorubicin (S.I = 3.88). Derivatives 16a, 18c, 18d, 18f inhibit EGFR and HER-2 IC50 for EGFR of 0.043, 0.226, 0.388, 0.19 μM respectively and for HER-2 of 0.032, 0.144, 0.195, 0.201 μM respectively.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11003491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138444920","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