Journal of Enzyme Inhibition and Medicinal Chemistry最新文献

Exploring covalent inhibitors of SARS-CoV-2 main protease: from peptidomimetics to novel scaffolds.

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-02-06 DOI: 10.1080/14756366.2025.2460045

Noor Atatreh, Radwa E Mahgoub, Mohammad A Ghattas

引用次数: 0

Discovery of a selective and reversible LSD1 inhibitor with potent anticancer effects in vitro and in vivo.

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-02-20 DOI: 10.1080/14756366.2025.2466093

Xiao-Song Zhang, Jin-Zhan Liu, Ying-Ying Mei, Meng Zhang, Li-Wei Sun

{"title":"Discovery of a selective and reversible LSD1 inhibitor with potent anticancer effects in vitro and in vivo.","authors":"Xiao-Song Zhang, Jin-Zhan Liu, Ying-Ying Mei, Meng Zhang, Li-Wei Sun","doi":"10.1080/14756366.2025.2466093","DOIUrl":"10.1080/14756366.2025.2466093","url":null,"abstract":"Lysine-specific demethylase 1 (LSD1) is abnormally overexpressed in various tumour tissues of patients and has been an attractive anticancer target. In this work, a potent LSD1 inhibitor (compound 14) was designed and synthesised by the molecular hybridisation strategy. It displays the potent antiproliferative activity against HepG2, HEP3B, HUH6, and HUH7 cells with IC50 values of 0.93, 2.09, 1.43, and 4.37 μM, respectively. Furthermore, compound 14 is a selective and reversible LSD1 inhibitor with an IC50 value of 0.18 μM and increases the methylation levels of H3K4me1/2. Molecular docking studies showed that it formed hydrogen bonds, hydrophilic interactions and hydrophobic interactions with residues of LSD1. Anticancer mechanisms demonstrated that it suppresses migration and epithelial-mesenchymal transition process in HepG2 cells. Importantly, it exhibits potent anti-liver cancer effects in vivo without obvious toxic effects. These interesting findings suggested that compound 14, a novel LSD1 inhibitor, may be a promising therapeutic agent to treat liver cancer.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2466093"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458176","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

Identification of novel inhibitors of dengue viral NS5 RNA-dependent RNA polymerase through molecular docking, biological activity evaluation and molecular dynamics simulations.

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-02-12 DOI: 10.1080/14756366.2025.2463006

Keli Zong, Chaochun Wei, Wei Li, Cong Wang, Jiajun Ruan, Xiaojing Liu, Susu Zhang, Hong Yan, Ruiyuan Cao, Xingzhou Li

{"title":"Identification of novel inhibitors of dengue viral NS5 RNA-dependent RNA polymerase through molecular docking, biological activity evaluation and molecular dynamics simulations.","authors":"Keli Zong, Chaochun Wei, Wei Li, Cong Wang, Jiajun Ruan, Xiaojing Liu, Susu Zhang, Hong Yan, Ruiyuan Cao, Xingzhou Li","doi":"10.1080/14756366.2025.2463006","DOIUrl":"10.1080/14756366.2025.2463006","url":null,"abstract":"The DENV-NS5 RNA-dependent RNA polymerase (RdRp) is essential for viral replication, and one of the targets of anti-virus. In this study, the Uni-VSW module was used to virtual screen 1.6 million compounds in the ChemDiv and TargetMol (USA) database, 27 candidates were obtained. Thereby 23 candidates were selected based on their binding free energies by 50 ns MD simulations. The biological activity of the candidates and the reference compounds (BCX4430 and Compound 27) were evaluated on their IC50 values against DENV-NGC, CC50 values, and selectivity index. Among these, the IC50 values of D1 and D8 were 13.06 ± 1.17 μM and 14.79 ± 7.76 μM, respectively, which were better than that of Compound 27 (IC50 =19.67 ± 1.12 μM). The comprehensive MD simulations were performed on the candidates to assess the stability behaviour and binding mechanisms. The density functional theory (DFT) analysis was also conducted to explore the structural and electronic properties.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2463006"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399453","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

Development of ketobenzothiazole-based peptidomimetic TMPRSS13 inhibitors with low nanomolar potency.

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-02-20 DOI: 10.1080/14756366.2025.2466841

Alexandre Joushomme, Antoine Désilets, William Champagne, Malihe Hassanzadeh, Gabriel Lemieux, Alice Gravel-Trudeau, Matthieu Lepage, Sabrina Lafrenière, Ulrike Froehlich, Karin List, Pierre-Luc Boudreault, Richard Leduc

{"title":"Development of ketobenzothiazole-based peptidomimetic TMPRSS13 inhibitors with low nanomolar potency.","authors":"Alexandre Joushomme, Antoine Désilets, William Champagne, Malihe Hassanzadeh, Gabriel Lemieux, Alice Gravel-Trudeau, Matthieu Lepage, Sabrina Lafrenière, Ulrike Froehlich, Karin List, Pierre-Luc Boudreault, Richard Leduc","doi":"10.1080/14756366.2025.2466841","DOIUrl":"10.1080/14756366.2025.2466841","url":null,"abstract":"TMPRSS13, a member of the Type II Transmembrane Serine Proteases (TTSP) family, is involved in cancer progression and in respiratory virus cell entry. To date, no inhibitors have been specifically developed for this protease. In this study, a chemical library of 65 ketobenzothiazole-based peptidomimetic molecules was screened against a proteolytically active form of recombinant TMPRSS13 to identify novel inhibitors. Following an initial round of screening, subsequent synthesis of additional derivatives supported by molecular modelling revealed important molecular determinants involved in TMPRSS13 inhibition. One inhibitor, N-0430, achieved low nanomolar affinity towards TMPRSS13 activity in a cellular context. Using a SARS-CoV-2 pseudovirus cell entry model, we further demonstrated the ability of N-0430 to block TMPRSS13-dependent entry of the pseudovirus. The identified peptidomimetic inhibitors and the molecular insights into their potency gained from this study will aid in the development of specific TMPRSS13 inhibitors.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2466841"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458173","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

Ferroptosis and hearing loss: from molecular mechanisms to therapeutic interventions.

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-02-24 DOI: 10.1080/14756366.2025.2468853

Xingyi Lv, Chenyi Yang, Xianying Li, Yun Liu, Yu Yang, Tongyan Jin, Zhijian Chen, Jinjing Jia, Min Wang, Li Li

引用次数: 0

Bioactivity profiling of Sanghuangporus lonicerinus: antioxidant, hypoglycaemic, and anticancer potential via in-vitro and in-silico approaches.

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-02-24 DOI: 10.1080/14756366.2025.2461185

Yusufjon Gafforov, Sofija Bekić, Manzura Yarasheva, Jovana Mišković, Nemanja Živanović, Jia Jia Chen, Edward Petri, Bekhzod Abdullaev, Sylvie Rapior, Young Won Lim, Ikram Abdullaev, Arshad Mehmood Abbasi, Soumya Ghosh, Wan Abd Al Qadr Imad Wan-Mohtar, Milena Rašeta

{"title":"Bioactivity profiling of Sanghuangporus lonicerinus: antioxidant, hypoglycaemic, and anticancer potential via in-vitro and in-silico approaches.","authors":"Yusufjon Gafforov, Sofija Bekić, Manzura Yarasheva, Jovana Mišković, Nemanja Živanović, Jia Jia Chen, Edward Petri, Bekhzod Abdullaev, Sylvie Rapior, Young Won Lim, Ikram Abdullaev, Arshad Mehmood Abbasi, Soumya Ghosh, Wan Abd Al Qadr Imad Wan-Mohtar, Milena Rašeta","doi":"10.1080/14756366.2025.2461185","DOIUrl":"10.1080/14756366.2025.2461185","url":null,"abstract":"This study investigates the mycochemical profile and biological activities of hydroethanolic (EtOH), chloroform (CHCl3), and hot water (H2O) extracts of Sanghuangporus lonicerinus from Uzbekistan. Antioxidant capacity was assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), NO, and FRAP assays, and in vitro hypoglycaemic effects were evaluated through α-amylase and α-glucosidase inhibition. Antiproliferative potential was explored by analysing the binding affinities of EtOH and H2O extracts to estrogen receptor α (ERα), ERβ, androgen receptor (AR), and glucocorticoid receptor (GR), with molecular docking providing structural insights. LC-MS/MS analysis revealed solvent-dependent phenolic profiles, with the EtOH extract containing the highest total phenolic content (143.15 ± 6.70 mg GAE/g d.w.) and the best antioxidant capacity. The EtOH extract showed significant hypoglycaemic effects, with 85.29 ± 5.58% inhibition of α-glucosidase and 41.21 ± 0.79% inhibition of α-amylase. Moderate ERβ binding suggests potential for estrogen-mediated cancer therapy, while strong AKR1C3 inhibition by the EtOH extract supports its therapeutic potential.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2461185"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483233","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

Identification of a novel pyrrolo[2,3-b]pyridine compound as a potent glycogen synthase kinase 3β inhibitor for treating Alzheimer's disease.

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-02-20 DOI: 10.1080/14756366.2025.2466846

Qing-Qing Xun, Jing Zhang, Lei Feng, Yu-Ying Ma, Ying Li, Xiao-Long Shi

{"title":"Identification of a novel pyrrolo[2,3-b]pyridine compound as a potent glycogen synthase kinase 3β inhibitor for treating Alzheimer's disease.","authors":"Qing-Qing Xun, Jing Zhang, Lei Feng, Yu-Ying Ma, Ying Li, Xiao-Long Shi","doi":"10.1080/14756366.2025.2466846","DOIUrl":"10.1080/14756366.2025.2466846","url":null,"abstract":"Herein, a novel pyrrolo[2,3-b]pyridine-based glycogen synthase kinase 3β (GSK-3β) inhibitor, S01, was rationally designed and synthesised to target Alzheimer's disease (AD). S01 inhibited GSK-3β, with an IC50 of 0.35 ± 0.06 nM, and had an acceptable kinase selectivity for 24 structurally similar kinases. Western blotting assays indicated that S01 efficiently increased the expression of p-GSK-3β-Ser9 and decreased p-tau-Ser396 levels in a dose-dependent manner. In vitro cell experiments, S01 showed low cytotoxicity to SH-SY5Y cells, significantly upregulated the expression of β-catenin and neurogenesis-related biomarkers, and effectively promoted the outgrowth of differentiated neuronal neurites. Moreover, S01 substantially ameliorated dyskinesia in AlCl3-induced zebrafish AD models at a concentration of 0.12 μM, which was more potent than Donepezil (8 μM) under identical conditions. Acute toxicity experiments further confirmed the safety of S01 in vivo. Our findings suggested that S01 is a prospective GSK-3β inhibitor and can be tested as a candidate for treating AD.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2466846"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458178","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

Chemical composition, antioxidant activities, and enzyme inhibitory effects of Lespedeza bicolour Turcz. essential oil.

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-02-06 DOI: 10.1080/14756366.2025.2460053

Jiadong Zhu, Ziyue Xu, Xu Liu

{"title":"Chemical composition, antioxidant activities, and enzyme inhibitory effects of Lespedeza bicolour Turcz. essential oil.","authors":"Jiadong Zhu, Ziyue Xu, Xu Liu","doi":"10.1080/14756366.2025.2460053","DOIUrl":"10.1080/14756366.2025.2460053","url":null,"abstract":"Lespedeza bicolour Turcz. is a traditional medicinal plant with a wide range of ethnomedicinal values. The main components of L. bicolour essential oil (EO) were β-pinene (15.41%), β-phellandrene (12.43%), and caryophyllene (7.79%). The EO of L. bicolour showed antioxidant activity against ABTS radical and DPPH radical with an IC50 value of 0.69 ± 0.03 mg/mL and 10.44 ± 2.09 mg/mL, respectively. The FRAP antioxidant value was 81.96 ± 6.17 μmol/g. The EO had activities against acetylcholinesterase, α-glucosidase, and β-lactamase with IC50 values of 309.30 ± 11.16 μg/mL, 360.47 ± 35.67 μg/mL, and 27.54 ± 1.21 μg/mL, respectively. Molecular docking showed methyl dehydroabietate docked well with all tested enzymes. Sclareol and (+)-borneol acetate showed the strongest binding affinity to α-glucosidase and β-lactamase, respectively. The present study provides a direction for searching enzyme inhibitors for three tested enzymes and shows L. bicolour EO possesses the potential to treat a series of diseases.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2460053"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11803819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255800","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

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

Rational design, synthesis, and molecular modelling insights of dual DNA binders/DHFR inhibitors bearing arylidene-hydrazinyl-1,3-thiazole scaffold with apoptotic and anti-migratory potential in breast MCF-7 cancer cells.

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-03-04 DOI: 10.1080/14756366.2025.2468353

Marwa H El-Wakil, Rasha A Ghazala, Hadeel A El-Dershaby, Danuta Drozdowska, Agnieszka Wróbel-Tałałaj, Cezary Parzych, Artur Ratkiewicz, Beata Kolesińska, Heba A Abd El-Razik, Farid S G Soliman

{"title":"Rational design, synthesis, and molecular modelling insights of dual DNA binders/DHFR inhibitors bearing arylidene-hydrazinyl-1,3-thiazole scaffold with apoptotic and anti-migratory potential in breast MCF-7 cancer cells.","authors":"Marwa H El-Wakil, Rasha A Ghazala, Hadeel A El-Dershaby, Danuta Drozdowska, Agnieszka Wróbel-Tałałaj, Cezary Parzych, Artur Ratkiewicz, Beata Kolesińska, Heba A Abd El-Razik, Farid S G Soliman","doi":"10.1080/14756366.2025.2468353","DOIUrl":"10.1080/14756366.2025.2468353","url":null,"abstract":"In light of searching for new breast cancer therapies, DNA-targeted small molecules were rationally designed to simultaneously bind DNA and inhibit human dihydrofolate reductase (hDHFR). Fourteen new arylidene-hydrazinyl-1,3-thiazoles (5-18) were synthesised and their dual DNA groove binding potential and in vitro hDHFR inhibition were performed. Two compounds, 5 and 11, proved their dual efficacy. Molecular docking and molecular dynamics simulations were performed for those active derivatives to explore their mode of binding and stability of interactions inside DHFR active site. Anti-breast cancer activity was assessed for 5 and 11 on MCF-7 cells using MTX as reference. IC50 measurements revealed that both compounds were more potent and selective than MTX. Cytotoxicity was examined against normal skin fibroblasts to examine safety and selectivity Moreover, mechanistic studies including apoptosis induction and wound healing were performed. Further in silico ADMET assessment was conducted to determine their eligibility as drug leads suitable for future optimisation and development.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2468353"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542164","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