Journal of Enzyme Inhibition and Medicinal Chemistry最新文献

Indirubin-3'-oxime as a dual-action agent: mitigating heat-induced male infertility in Drosophila melanogaster and inhibiting soluble epoxide hydrolase. 靛玉红-3′-肟作为双作用剂：缓解黑颊果蝇热致雄性不育和抑制可溶性环氧化物水解酶。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-01-22 DOI: 10.1080/14756366.2024.2447719

Nguyen Viet Phong, Hyo-Sung Kim, Yan Zhao, Eunbyul Yeom, Seo Young Yang

{"title":"Indirubin-3'-oxime as a dual-action agent: mitigating heat-induced male infertility in Drosophila melanogaster and inhibiting soluble epoxide hydrolase.","authors":"Nguyen Viet Phong, Hyo-Sung Kim, Yan Zhao, Eunbyul Yeom, Seo Young Yang","doi":"10.1080/14756366.2024.2447719","DOIUrl":"10.1080/14756366.2024.2447719","url":null,"abstract":"This study investigated the potential of the indirubin-3'-oxime (I3O) compound to mitigate temperature-induced male infertility in Drosophila melanogaster. Elevated temperatures significantly reduced egg-hatching rates, but I3O supplementation improved these rates, suggesting it can partially restore fertility under heat stress. Additionally, I3O was found to inhibit soluble epoxide hydrolase (sEH), an enzyme involved in the metabolism of epoxyeicosatrienoic acids, which are vital for reproductive health. I3O exhibited sEH inhibitions with an IC50 value of 59.74 ± 0.41 µM. Enzyme kinetics revealed that I3O acts as a non-competitive inhibitor of sEH with a Ki value of 78.88 µM. Molecular docking showed strong interactions between I3O and key residues in the allosteric regions within the sEH enzyme, with a binding affinity of -9.2 kcal/mol. These interactions were supported by 100 ns molecular dynamics simulations, which confirmed the stability of the sEH-I3O complex.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2447719"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006501","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

Small molecules targeting the eubacterial β-sliding clamp discovered by combined in silico and in vitro screening approaches. 通过硅内和体外联合筛选方法发现了靶向真菌性β-滑动钳的小分子。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-01-03 DOI: 10.1080/14756366.2024.2440861

Alessia Caputo, Gian Marco Elisi, Elisabetta Levati, Giulia Barotti, Sara Sartini, Jerome Wagner, Dominique Y Burnouf, Simone Ottonello, Silvia Rivara, Barbara Montanini

{"title":"Small molecules targeting the eubacterial β-sliding clamp discovered by combined in silico and in vitro screening approaches.","authors":"Alessia Caputo, Gian Marco Elisi, Elisabetta Levati, Giulia Barotti, Sara Sartini, Jerome Wagner, Dominique Y Burnouf, Simone Ottonello, Silvia Rivara, Barbara Montanini","doi":"10.1080/14756366.2024.2440861","DOIUrl":"https://doi.org/10.1080/14756366.2024.2440861","url":null,"abstract":"Antibiotic resistance stands as the foremost post-pandemic threat to public health. The urgent need for new, effective antibacterial treatments is evident. Protein-protein interactions (PPIs), owing to their pivotal role in microbial physiology, emerge as novel and attractive targets. Particularly promising is the α-subunit/β-sliding clamp interaction, crucial for the replicative competence of bacterial DNA polymerase III holoenzyme. Through pharmacophore-based virtual screening, we identified 4,000 candidate small molecule inhibitors targeting the β-clamp binding pocket. Subsequently, these candidates underwent evaluation using the BRET assay in yeast cells. Following this, three hits and 28 analogues were validated via Protein Thermal Shift and competitive ELISA assays. Among them, thiazolo[4,5-d]-pyrimidinedione and benzanilide derivatives exhibited micromolar potency in displacing the β-clamp protein partner and inhibiting DNA replication. This screening campaign unveiled new chemical classes of α/β-clamp PPI disruptors capable of inhibiting DNA polymerase III activity, which lend themselves for further optimisation to improve their antibacterial efficacy.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2440861"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921611","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

The new thiazolidine-2,4-dione-based hybrids with promising antimycobacterial activity: design, synthesis, biological evaluation, and drug interaction analysis. 具有良好抑菌活性的新型噻唑烷-2,4-二酮基杂合体：设计、合成、生物学评价和药物相互作用分析。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-01-03 DOI: 10.1080/14756366.2024.2442703

Nazar Trotsko, Agnieszka Głogowska, Barbara Kaproń, Katarzyna Kozieł, Ewa Augustynowicz-Kopeć, Agata Paneth

{"title":"The new thiazolidine-2,4-dione-based hybrids with promising antimycobacterial activity: design, synthesis, biological evaluation, and drug interaction analysis.","authors":"Nazar Trotsko, Agnieszka Głogowska, Barbara Kaproń, Katarzyna Kozieł, Ewa Augustynowicz-Kopeć, Agata Paneth","doi":"10.1080/14756366.2024.2442703","DOIUrl":"https://doi.org/10.1080/14756366.2024.2442703","url":null,"abstract":"The ever-increasing drug-resistant tuberculosis (TB) has invigorated the focus on the discovery and development of novel therapeutic agents and treatment options. Thiazolidinone-based compounds have shown good antitubercular properties in vitro. Here, we report the design and synthesis of a number of new derivatives inspired by the structure of thiazolidine-2,4-dione (TZD). The TZD-based hybrids with the thiosemicarbazone or the pyridinecarbohydrazone moiety were synthesised and their antimycobacterial activity was investigated against the reference H37Rv and two wild Mycobacterium tuberculosis (Mtb) strains. In further studies, a two-drug interaction analysis was also performed for assessing their synergism with the current first-line drugs used for the treatment of TB. It was found that some of the compounds showed high antimycobacterial activity with MICs (0.078-0.283 µM) and a synergistic effect with isoniazid or rifampicin, thereby demonstrating their potential as a promising scaffold for the development of novel coadjuvants for the effective treatment of TB.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2442703"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921572","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

Structural comparison of substrate-binding pockets of serine β-lactamases in classes A, C, and D. A、C和D类丝氨酸β-内酰胺酶底物结合袋的结构比较。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2024-12-23 DOI: 10.1080/14756366.2024.2435365

Hyeonmin Lee, Hyunjae Park, Kiwoong Kwak, Chae-Eun Lee, Jiwon Yun, Donghyun Lee, Jung Hun Lee, Sang Hee Lee, Lin-Woo Kang

{"title":"Structural comparison of substrate-binding pockets of serine β-lactamases in classes A, C, and D.","authors":"Hyeonmin Lee, Hyunjae Park, Kiwoong Kwak, Chae-Eun Lee, Jiwon Yun, Donghyun Lee, Jung Hun Lee, Sang Hee Lee, Lin-Woo Kang","doi":"10.1080/14756366.2024.2435365","DOIUrl":"https://doi.org/10.1080/14756366.2024.2435365","url":null,"abstract":"β-lactams have been the most successful antibiotics, but the rise of multi-drug resistant (MDR) bacteria threatens their effectiveness. Serine β-lactamases (SBLs), among the most common causes of resistance, are classified as A, C, and D, with numerous variants complicating structural and substrate spectrum comparisons. This study compares representative SBLs of these classes, focusing on the substrate-binding pocket (SBP). SBP is kidney bean-shaped on the indented surface, formed mainly by loops L1, L2, and L3, and an additional loop Lc in class C. β-lactams bind in a conserved orientation, with the β-lactam ring towards L2 and additional rings towards the space between L1 and L3. Structural comparison shows each class has distinct SBP structures, but subclasses share a conserved scaffold. The SBP structure, accommodating complimentary β-lactams, determines the substrate spectrum of SBLs. The systematic comparison of SBLs, including structural compatibility between β-lactams and SBPs, will help understand their substrate spectrum.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2435365"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877318","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

In-cell bioluminescence resonance energy transfer (BRET)-based assay uncovers ceritinib and CA-074 as SARS-CoV-2 papain-like protease inhibitors. 基于细胞内生物发光共振能量转移（BRET）的检测发现 Ceritinib 和 CA-074 是 SARS-CoV-2 类木瓜蛋白酶抑制剂。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-08-20 DOI: 10.1080/14756366.2024.2387417

Mei Li, Zhu-Chun Bei, Yongtian Yuan, Baogang Wang, Dongna Zhang, Likun Xu, Liangliang Zhao, Qin Xu, Yabin Song

{"title":"In-cell bioluminescence resonance energy transfer (BRET)-based assay uncovers ceritinib and CA-074 as SARS-CoV-2 papain-like protease inhibitors.","authors":"Mei Li, Zhu-Chun Bei, Yongtian Yuan, Baogang Wang, Dongna Zhang, Likun Xu, Liangliang Zhao, Qin Xu, Yabin Song","doi":"10.1080/14756366.2024.2387417","DOIUrl":"10.1080/14756366.2024.2387417","url":null,"abstract":"Papain-like protease (PLpro) is an attractive anti-coronavirus target. The development of PLpro inhibitors, however, is hampered by the limitations of the existing PLpro assay and the scarcity of validated active compounds. We developed a novel in-cell PLpro assay based on BRET and used it to evaluate and discover SARS-CoV-2 PLpro inhibitors. The developed assay demonstrated remarkable sensitivity for detecting the reduction of intracellular PLpro activity while presenting high reliability and performance for inhibitor evaluation and high-throughput screening. Using this assay, three protease inhibitors were identified as novel PLpro inhibitors that are structurally disparate from those previously known. Subsequent enzymatic assays and ligand-protein interaction analysis based on molecular docking revealed that ceritinib directly inhibited PLpro, showing high geometric complementarity with the substrate-binding pocket in PLpro, whereas CA-074 methyl ester underwent intracellular hydrolysis, exposing a free carboxyhydroxyl group essential for hydrogen bonding with G266 in the BL2 groove, resulting in PLpro inhibition.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2387417"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008884","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

Synthesis and biological evaluation of quinoxaline derivatives as ASK1 inhibitors. 作为 ASK1 抑制剂的喹喔啉衍生物的合成和生物学评价。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-10-21 DOI: 10.1080/14756366.2024.2414382

Xiaorui Han, Pingping Lan, Qianfeng Chen, Hua Liu, Zhongwen Chen, Tiantian Wang, Zengtao Wang

引用次数: 0

Vitamin B6 inhibits activity of Helicobacter pylori adenylosuccinate synthetase and growth of reference and clinical, antibiotic-resistant H. pylori strains. 维生素 B6 可抑制幽门螺旋杆菌腺苷琥珀酸合成酶的活性以及参考菌株和临床抗生素耐药幽门螺旋杆菌菌株的生长。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-08-16 DOI: 10.1080/14756366.2024.2372734

Marta Ilona Wojtyś, Weronika Maksymiuk, Marta Narczyk, Ante Bubić, Ivana Leščić Ašler, Paweł Krzyżek, Grażyna Gościniak, Elżbieta Katarzyna Jagusztyn-Krynicka, Agnieszka Bzowska

{"title":"Vitamin B6 inhibits activity of Helicobacter pylori adenylosuccinate synthetase and growth of reference and clinical, antibiotic-resistant H. pylori strains.","authors":"Marta Ilona Wojtyś, Weronika Maksymiuk, Marta Narczyk, Ante Bubić, Ivana Leščić Ašler, Paweł Krzyżek, Grażyna Gościniak, Elżbieta Katarzyna Jagusztyn-Krynicka, Agnieszka Bzowska","doi":"10.1080/14756366.2024.2372734","DOIUrl":"10.1080/14756366.2024.2372734","url":null,"abstract":"The current therapies against gastric pathogen Helicobacter pylori are ineffective in over 20% of patients. Enzymes belonging to the purine salvage pathway are considered as novel drug targets in this pathogen. Therefore, the main aim of the current study was to determine the antibacterial activity of pyridoxal 5'-phosphate (PLP), an active form of vitamin B6, against reference and clinical strains of H. pylori. Using a broad set of microbiological, physicochemical (UV absorption, LC-MS, X-ray analysis) and in silico experiments, we were able to prove that PLP inhibits adenylosuccinate synthetase (AdSS) from H. pylori by the competition with GTP (IC50eq ∼30 nM). This behaviour was attributed to formation of a Schiff base with a lysine residue (a covalent bond with Lys322 in the GTP binding site of AdSS) and was potentiated by the presence of vitamin C. This antibacterial activity of PLP gives hope for its future use against H. pylori.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2372734"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988056","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

Novel anti-neuroinflammatory pyranone-carbamate derivatives as selective butyrylcholinesterase inhibitors for treating Alzheimer's disease. 作为选择性丁酰胆碱酯酶抑制剂治疗阿尔茨海默病的新型抗神经炎吡喃酮-氨基甲酸酯衍生物。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-02-16 DOI: 10.1080/14756366.2024.2313682

Chuanyu Yu, Xueyan Liu, Bingxiang Ma, Jiexin Xu, Yiquan Chen, Chaoxian Dai, Huaping Peng, Daijun Zha

{"title":"Novel anti-neuroinflammatory pyranone-carbamate derivatives as selective butyrylcholinesterase inhibitors for treating Alzheimer's disease.","authors":"Chuanyu Yu, Xueyan Liu, Bingxiang Ma, Jiexin Xu, Yiquan Chen, Chaoxian Dai, Huaping Peng, Daijun Zha","doi":"10.1080/14756366.2024.2313682","DOIUrl":"10.1080/14756366.2024.2313682","url":null,"abstract":"Butyrylcholinesterase (BuChE) and neuroinflammation have recently emerged as promising therapeutic directions for Alzheimer's disease (AD). Herein, we synthesised 19 novel pyranone-carbamate derivatives and evaluated their activities against cholinesterases and neuroinflammation. The optimal compound 7p exhibited balanced BuChE inhibitory activity (eqBuChE IC50 = 4.68 nM; huBuChE IC50 = 9.12 nM) and anti-neuroinflammatory activity (NO inhibition = 28.82% at 10 μM, comparable to hydrocortisone). Enzyme kinetic and docking studies confirmed compound 7p was a mix-type BuChE inhibitor. Additionally, compound 7p displayed favourable drug-likeness properties in silico prediction, and exhibited high BBB permeability in the PAMPA-BBB assay. Compound 7p had good safety in vivo as verified by an acute toxicity assay (LD50 > 1000 mg/kg). Most importantly, compound 7p effectively mitigated cognitive and memory impairments in the scopolamine-induced mouse model, showing comparable effects to Rivastigmine. Therefore, we envisioned that compound 7p could serve as a promising lead compound for treating AD.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2313682"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10878344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139741200","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

Correction. 更正。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-07-29 DOI: 10.1080/14756366.2024.2374156

引用次数: 0

Design and synthesis of triazolopyridine derivatives as potent JAK/HDAC dual inhibitors with broad-spectrum antiproliferative activity. 设计和合成具有广谱抗增殖活性的强效 JAK/HDAC 双抑制剂三唑吡啶衍生物。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-10-08 DOI: 10.1080/14756366.2024.2409771

Zhengshui Xu, Changchun Ye, Xingjie Wang, Ranran Kong, Zilu Chen, Jing Shi, Xin Chen, Shiyuan Liu

引用次数: 0