Journal of Enzyme Inhibition and Medicinal Chemistry最新文献_第7页

Bio-guided discovery of antibacterial metabolites from Penicillium chrysogenum. 生物引导下发现青霉菌的抗菌代谢物。

IF 5.4 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-08-26 DOI: 10.1080/14756366.2025.2547258

Amira Mira, Fatma M Abdel Bar, Ahmed I Foudah, Mohamed H Aboutaleb, Tarek S Ibrahim, Ahmed H E Hassan, Ashraf T Khalil

{"title":"Bio-guided discovery of antibacterial metabolites from Penicillium chrysogenum.","authors":"Amira Mira, Fatma M Abdel Bar, Ahmed I Foudah, Mohamed H Aboutaleb, Tarek S Ibrahim, Ahmed H E Hassan, Ashraf T Khalil","doi":"10.1080/14756366.2025.2547258","DOIUrl":"https://doi.org/10.1080/14756366.2025.2547258","url":null,"abstract":"Bio-guided isolation from the Red Sea-derived Penicillium chrysogenum yielded two new metabolites, 15-deoxy-15-amino-citreohybridonol (6) and chrysogenotoxin (7), alongside five known compounds: emodin (1), chrysophanol (2), bis(2-ethylhexyl) phthalate (3), haenamindole (4), and citreorosein (5). Compound 6 exhibited broad-spectrum antibacterial activity against both Gram-positive (MIC: 0.31-0.62 μM; MBC: 0.31-0.62 μM) and Gram-negative bacteria (MIC: 0.15-1.25 μM; MBC: 0.62-2.5 μM). Compound 7 showed potent bactericidal activity against Gram-negative bacteria (MIC: 0.07-0.31 μM; MBC: 0.15-0.62 μM) with MBC/MIC ≤ 4, while compound 4 selectively inhibited S. pneumoniae (MIC: 0.31 μM; MBC: 0.62 μM). Compounds 4, 6, and 7 exhibited low cytotoxicity towards human intestinal epithelial cells (HIEC-6). Molecular docking studies targeting the NDM-1 β-lactamase identified compounds 4, 6, and 7 as potential inhibitors of New Delhi metallo-β-lactamase-1 (NDM-1). Molecular dynamics simulations confirmed the structural stability of 7 within the NDM-1 active site. Chrysogenotoxin (7) was suggested as a promising antibacterial candidate against antibiotic-resistant pathogens.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2547258"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956667","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 novel benzamide class I selective lysine deacetylase inhibitors as potent anticancer agents. 新型苯甲酰胺I类选择性赖氨酸去乙酰化酶抑制剂的研制。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-07-01 DOI: 10.1080/14756366.2025.2520612

Jason H Gill, Jonathan D Sellars, Paul G Waddell, Steven D Shnyder, Ronald Grigg, Colin W G Fishwick

{"title":"Development of novel benzamide class I selective lysine deacetylase inhibitors as potent anticancer agents.","authors":"Jason H Gill, Jonathan D Sellars, Paul G Waddell, Steven D Shnyder, Ronald Grigg, Colin W G Fishwick","doi":"10.1080/14756366.2025.2520612","DOIUrl":"10.1080/14756366.2025.2520612","url":null,"abstract":"Small molecule inhibitors of lysine deacetylases (KDACs), exemplified by histone deacetylases (HDACs), exhibit significant promise as cancer therapeutics. Using a modular combinatorial chemistry approach, a novel class of KDAC inhibitors (KDACi) containing the aminophenyl-benzamide headgroup have been developed, which incorporate a vinyl group within the linker region for active site stabilisation and a trifluoromethyl moiety within the capping group to exploit enzyme surface topology. Consequently, a class I selective KDACi (7) with a preference towards HDAC1 over other class I KDACs was identified. This KDACi orientates differently within the KDAC active site and exhibits an improved antitumour profile relative to the benchmark class I selective KDACi Entinostat (1). The clinical potential of 7 is further exemplified by the inhibition of tumour growth in an in vivo model of ovarian cancer. These results offer significant scope for the rational development of KDACi with improved selectivity against specific KDAC and widespread therapeutic potential.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2520612"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12217109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540460","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

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

Identification of broad-spectrum M^pro inhibitors: a focus on high-risk coronaviruses and conserved interactions. 广谱Mpro抑制剂的鉴定：重点关注高风险冠状病毒和保守相互作用

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-05-21 DOI: 10.1080/14756366.2025.2503961

Man Liu, Li Zhao, Xupeng Huang, Zhenhao Tang, Yihang Zhong, Mengrong Yan, Shun Liu, Shunjing Wang, Zeyun Sun, Zixuan Rao, Linyi Yu, Yuying Fang, Wei Zhang, Hongbo Zhang, Wei Peng

{"title":"Identification of broad-spectrum Mpro inhibitors: a focus on high-risk coronaviruses and conserved interactions.","authors":"Man Liu, Li Zhao, Xupeng Huang, Zhenhao Tang, Yihang Zhong, Mengrong Yan, Shun Liu, Shunjing Wang, Zeyun Sun, Zixuan Rao, Linyi Yu, Yuying Fang, Wei Zhang, Hongbo Zhang, Wei Peng","doi":"10.1080/14756366.2025.2503961","DOIUrl":"10.1080/14756366.2025.2503961","url":null,"abstract":"The COVID-19 pandemic underscores the urgent need to develop broad-spectrum antivirals against coronaviruses (CoVs) to prepare for future outbreaks. In this study, we presented a systematic approach to developing broad-spectrum Mpro inhibitors, with a focus on high-risk CoVs. We optimised S-217622 as a lead compound, with the goal of enhancing conserved interactions within the S1, S2, and S3/S4 pockets of Mpro, leading to significantly improved inhibitory potency against representative CoVs. Compound 25 exhibited submicromolar activity across all ten CoVs, with IC50 values below 0.1 μM for six of them. The X-ray co-crystal structure of SARS-CoV-2 Mpro in complex with compound 25 revealed the structural basis of conserved interactions contributing to its broad-spectrum activity. This study demonstrates the feasibility of reinforcing conserved interactions to develop Mpro inhibitors with broad-spectrum activity and provides valuable strategies for combating future pandemics caused by unknown CoVs.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2503961"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110509","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

Liquidambaric acid as a non-competitive α-glucosidase inhibitor: multi-level evidence from enzyme kinetics, molecular docking, molecular dynamics simulations, and a Drosophila hyperglycaemic model. 甘草酸作为一种非竞争性α-葡萄糖苷酶抑制剂：来自酶动力学、分子对接、分子动力学模拟和果蝇高血糖模型的多层次证据

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-04-29 DOI: 10.1080/14756366.2025.2497486

Liwei Jia, Yan Liu, Bo Fu, Yuan Tian, Xin Meng

{"title":"Liquidambaric acid as a non-competitive α-glucosidase inhibitor: multi-level evidence from enzyme kinetics, molecular docking, molecular dynamics simulations, and a Drosophila hyperglycaemic model.","authors":"Liwei Jia, Yan Liu, Bo Fu, Yuan Tian, Xin Meng","doi":"10.1080/14756366.2025.2497486","DOIUrl":"https://doi.org/10.1080/14756366.2025.2497486","url":null,"abstract":"Liquidambaric acid, a pentacyclic triterpenoid from Liquidambar formosana Hance, was evaluated as a novel α-glucosidase inhibitor for type 2 diabetes mellitus (T2DM) management. Enzyme kinetic assays revealed its potent non-competitive inhibition (IC50 = 0.12 mM). Molecular docking showed stable hydrogen bonding at an allosteric site, altering enzyme conformation, while 100 ns molecular dynamics (MD) simulations confirmed the stability of the protein-ligand complex. In vivo, a Drosophila melanogaster hyperglycaemic model demonstrated significant glucose reduction, confirming its hypoglycaemic potential. ADMET analysis predicted favourable bioavailability and low toxicity, supporting its development as a safe therapeutic agent. These findings integrate enzyme kinetics, molecular modelling, MD simulations, and in vivo validation, highlighting liquidambaric acid's potential as a multifunctional and cost-effective agent for T2DM management.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2497486"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985791","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

2,5-Dihydroxyphenylethanone: an anti-melanogenic bioactive compound isolated from Ganoderma cochlear. 2,5-二羟基苯乙烷酮：一种从灵芝中分离的抗黑色素生成的生物活性化合物。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-04-29 DOI: 10.1080/14756366.2025.2495364

Meng Ning, Xiao-Cui Liu, Min He, Xing-Rong Peng, Ming-Hua Qiu

引用次数: 0

Identification of chemical scaffolds for targeting ubiquitin-specific protease 11 (USP11) through high-throughput virtual screening. 利用高通量虚拟筛选技术鉴定靶向泛素特异性蛋白酶11 （USP11）的化学支架

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-06-30 DOI: 10.1080/14756366.2025.2518191

Hobin Lee, Sunghoon Hurh, Soomin Kang, Jihwan Yoon, Jong-Ik Hwang, Derek T Logan, Hong-Rae Kim

{"title":"Identification of chemical scaffolds for targeting ubiquitin-specific protease 11 (USP11) through high-throughput virtual screening.","authors":"Hobin Lee, Sunghoon Hurh, Soomin Kang, Jihwan Yoon, Jong-Ik Hwang, Derek T Logan, Hong-Rae Kim","doi":"10.1080/14756366.2025.2518191","DOIUrl":"10.1080/14756366.2025.2518191","url":null,"abstract":"USP11 is a promising therapeutic target implicated in Alzheimer's disease and various cancers; however, no specific inhibitors are currently available, with the only known inhibitor being mitoxantrone, which primarily targets topoisomerase II. To identify novel chemical starting points, we conducted high-throughput virtual screening using a USP11 homology model. Screening over 600,000 compounds yielded five structurally distinct hits with significant inhibitory activity. Biochemical validation highlighted two promising scaffolds: benzoxadiazole derivatives and pyrrolo-phenylamidine analogues, both demonstrating structure-dependent inhibition and tractable SAR profiles. Docking studies further characterised their binding modes, supporting their potential for optimisation. Hydroxyphenyl hydrazone analogues raised PAINS-related concerns, while compounds such as squalamine were deprioritized due to weak binding affinity and structural complexity. Overall, this study provides valuable scaffolds and mechanistic insights that can inform future development of potent, selective USP11 inhibitors.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2518191"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528161","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

A study of flavonoid inhibitors against Monkeypox H1 phosphatase. 猴痘H1磷酸酶类黄酮抑制剂的研究。

IF 5.4 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-08-12 DOI: 10.1080/14756366.2025.2535585

Hwa Young Kim, Mi-Sun Kim, Dong Hae Shin

{"title":"A study of flavonoid inhibitors against Monkeypox H1 phosphatase.","authors":"Hwa Young Kim, Mi-Sun Kim, Dong Hae Shin","doi":"10.1080/14756366.2025.2535585","DOIUrl":"10.1080/14756366.2025.2535585","url":null,"abstract":"Poxviruses regulate their replication cycle through host phosphorylation pathways, with dual-specific phosphatase H1(DUSP-H1) playing a key role in immune evasion by dephosphorylating STAT1 and inhibiting interferon(IFN) responses. Given its high conservation across orthopoxviruses, it represents a promising antiviral target. This study screened a flavonoid library against DUSP-H1 from monkeypox virus (mDUSP-H1) using a malachite green-based phosphatase assay, identifying Myricetin, (-)-Gallocatechin, Cupressuflavone, (-)-Epigallocatechin gallate, Baicalein, and Herbacetin as potent mDUSP-H1 inhibitors (IC50: 7.07-14.05 μM). Docking analysis revealed key hydrogen bonding interactions between 5,7-hydroxyl groups of the hydroxyflavone backbone and Asp79 and Arg116 of mDUSP-H1, respectively. Additional interactions with Ser23 via the 3'-hydroxyl group seems to enhance binding and effectively blocking the enzyme's active site. These findings align with previous studies on tyrosine phosphatase inhibitors, supporting flavonoids as broad-spectrum viral phosphatase inhibitors. Further structural and pharmacokinetic studies will aid in developing optimised antiviral therapies against monkeypox, variola, and cowpox viruses.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2535585"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821515","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

Nucleoside diphosphate kinase strongly promotes GDP and ADP metabolism in the cell and affects endogenous proton leak in mitochondria - the kinase is hampered by oxidative phosphorylation inhibitors. 核苷二磷酸激酶强烈促进细胞内GDP和ADP代谢，并影响线粒体内源性质子泄漏-该激酶受到氧化磷酸化抑制剂的阻碍。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-07-17 DOI: 10.1080/14756366.2025.2520611

Andrzej M Woyda-Ploszczyca

{"title":"Nucleoside diphosphate kinase strongly promotes GDP and ADP metabolism in the cell and affects endogenous proton leak in mitochondria - the kinase is hampered by oxidative phosphorylation inhibitors.","authors":"Andrzej M Woyda-Ploszczyca","doi":"10.1080/14756366.2025.2520611","DOIUrl":"10.1080/14756366.2025.2520611","url":null,"abstract":"Rapid GDP metabolism in mitochondria isolated from wild-type yeast is postulated. The hallmark of exogenous GDP is convergence with the effect of exogenous ADP, typically inducing oxidative phosphorylation (OXPHOS). The GDP-provoked changes in the presence of ATP, i.e. increased respiratory rate accompanied by decreased inner mitochondrial membrane electrical potential, were curtailed by OXPHOS inhibitors, such as carboxyatractyloside, which apparently merged the GDP effect with OXPHOS. However, all performed tests indicated that the response of mitochondria to GDP is indirect and involves two steps. First, GDP is transphosphorylated via nucleoside diphosphate kinase (NDPK), ATP + GDP → ADP + GTP, which is followed by ADP-induced OXPHOS. Importantly, in mitochondria isolated from mutant yeast with a deleted NDPK gene, the stimulatory effect of GDP was eliminated. Therefore, a prerequisite for GDP metabolic action is the cooperation of NDPK with the OXPHOS apparatus. This biological model can help elucidate the molecular basis of some diseases treatment, such as cancer.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2520611"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649519","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

Myeloperoxidase as a therapeutic target for oxidative damage in Alzheimer's disease. 髓过氧化物酶作为阿尔茨海默病氧化损伤的治疗靶点。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-02-14 DOI: 10.1080/14756366.2025.2456282

Astrid Mayleth Rivera Antonio, Itzia Irene Padilla Martínez, Mónica A Torres-Ramos, Martha Cecilia Rosales-Hernández

{"title":"Myeloperoxidase as a therapeutic target for oxidative damage in Alzheimer's disease.","authors":"Astrid Mayleth Rivera Antonio, Itzia Irene Padilla Martínez, Mónica A Torres-Ramos, Martha Cecilia Rosales-Hernández","doi":"10.1080/14756366.2025.2456282","DOIUrl":"10.1080/14756366.2025.2456282","url":null,"abstract":"Alzheimer's disease (AD) is a major neurodegenerative disorder more common in older adults. One of the leading AD hypotheses involves the amyloid beta (A) production, it is associated to oxidative stress, neuroinflammation, and neurovascular damage. The interaction of A with the blood vessel wall contributes to the disruption of the blood-brain barrier (BBB), allowing neutrophil infiltration containing the myeloperoxidase enzyme (MPO), which produces hypochlorous acid (HOCl) a potent oxidant. Also, MPO could be released from the microglia cells and interact with the amyloid beta plaques. This review aims to study the role of MPO in the progression of AD, in particular its contribution to oxidative stress and neuroinflammation. Furthermore, to explore the MPO-potential as AD-biomarker to evaluate the therapeutic potential of its inhibitors to mitigate the neurotoxicity. Finally, revise MPO inhibitors that could act as dual inhibitors acting on MPO and acetylcholinesterase and or another target involved in AD.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2456282"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414438","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