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

Profiling and cheminformatics bioprospection of curcurbitacin I and momordin Ic from Momordica balsamina on α-amylase and α-glucosidase. 苦瓜α-淀粉酶和α-葡萄糖苷酶活性分析及化学信息学生物展望。

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: 10.1080/14756366.2025.2492706

Viruska Jaichand, Adedayo Ayodeji Lanrewaju, Himansu Baijnath, Saheed Sabiu, Viresh Mohanlall

{"title":"Profiling and cheminformatics bioprospection of curcurbitacin I and momordin Ic from Momordica balsamina on α-amylase and α-glucosidase.","authors":"Viruska Jaichand, Adedayo Ayodeji Lanrewaju, Himansu Baijnath, Saheed Sabiu, Viresh Mohanlall","doi":"10.1080/14756366.2025.2492706","DOIUrl":"https://doi.org/10.1080/14756366.2025.2492706","url":null,"abstract":"Momordica spp. has been traditionally used to manage type 2 diabetes mellitus, but the mechanisms and metabolites remain unclear. This study evaluated the inhibitory potential of Momordica balsamina extracts on α-amylase and α-glucosidase in vitro, identifying cucurbitacin I and momordin Ic via high-performance liquid chromatography-photo diode array, and their inhibitory potential in silico. Ethyl acetate seed extract (14.46 µg/ml) and hexane fruit flesh extract (16.79 µg/ml) exhibited lower IC50 values against α-amylase and α-glucosidase, respectively, compared to acarbose (reference standard). Comparatively, momordin Ic concentrations (36.57-605.98 µg/ml) were higher than cucurbitacin I (17.08-44.34 µg/ml). A 140 ns simulation showed that cucurbitacin I (-63.06 kcal/mol) and momordin Ic (-66.53 kcal/mol) exhibited stronger binding to α-amylase than acarbose (-36.46 kcal/mol), whereas cucurbitacin I (-38.08 kcal/mol) and momordin Ic (-54.87 kcal/mol) displayed weaker binding to α-glucosidase, relative to acarbose (-63.73 kcal/mol). Generally, momordin Ic demonstrated better thermodynamic properties, hence further in vitro and in vivo studies are needed to validate their antidiabetic potential.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2492706"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022271","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

Activity guided discovery of dual inhibitors of α-glucosidase and β-glucuronidase from the leaves of Millettia pachycarpa Benth. 以活性为导向，从厚木叶中发现α-葡萄糖苷酶和β-葡萄糖苷酶双抑制剂。

IF 5.6 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-05-15 DOI: 10.1080/14756366.2025.2501041

Yanxi He, Huanran Xu, Shaoqian Tan, Jing Long, Hui Lei, Ling Xiao, Xiaoyi Qi, Mingming Deng, Xia Xiong, Jingcan You, Liangliang Zhu, Muhan Lü, Sicheng Liang

{"title":"Activity guided discovery of dual inhibitors of α-glucosidase and β-glucuronidase from the leaves of Millettia pachycarpa Benth.","authors":"Yanxi He, Huanran Xu, Shaoqian Tan, Jing Long, Hui Lei, Ling Xiao, Xiaoyi Qi, Mingming Deng, Xia Xiong, Jingcan You, Liangliang Zhu, Muhan Lü, Sicheng Liang","doi":"10.1080/14756366.2025.2501041","DOIUrl":"10.1080/14756366.2025.2501041","url":null,"abstract":"Type 2 diabetes mellitus (T2DM) and cancers are two globally prevalent diseases which can increase the incidence of each other. Intestinal α-glucosidase and β-glucuronidase are key targets for glycaemic control and chemotherapy detoxification, respectively. This study first found that the leaf methanol extract of Millettia pachycarpa displayed dual inhibition to the two enzymes. The dually active constituents were then isolated and identified as two prenylated isoflavones of 6,8-diprenylorobol and 6,8-diprenylgenistein. Diprenylorobol exhibits competitive inhibition to both the two enzymes with Ki values of 21.6 μM (α-glucosidase) and 1.41 μM (β-glucuronidase). Diprenylgenistein is an uncompetitive inhibitor of α-glucosidase (Ki = 11.4 μM) but a competitive inhibitor of β-glucuronidase (Ki = 1.69 μM). Molecular docking studies showed that both the two isoflavones tightly bind into the active pockets via various hydrogen bonds and hydrophobic interactions. In summary, the current study identifies two promising dual inhibitors of α-glucosidase and β-glucuronidase from the leaves of Millettia pachycarpa.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2501041"},"PeriodicalIF":5.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078334","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 eugenol derivatives with 5-LOX inhibitory activity. 具有5-LOX抑制活性的丁香酚衍生物的研究。

IF 5.4 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-08-21 DOI: 10.1080/14756366.2025.2535586

José L Pereira Filho, Renato B Pereira, Tatiana F Vieira, Sérgio F Sousa, José R A Coelho, Nuno F S Pinto, Catarina M M Coelho, Maria José G Fernandes, Elisabete M S Castanheira, Maria S T Gonçalves, David M Pereira

{"title":"Development of eugenol derivatives with 5-LOX inhibitory activity.","authors":"José L Pereira Filho, Renato B Pereira, Tatiana F Vieira, Sérgio F Sousa, José R A Coelho, Nuno F S Pinto, Catarina M M Coelho, Maria José G Fernandes, Elisabete M S Castanheira, Maria S T Gonçalves, David M Pereira","doi":"10.1080/14756366.2025.2535586","DOIUrl":"https://doi.org/10.1080/14756366.2025.2535586","url":null,"abstract":"Eugenol (4-allyl-2-methoxyphenol), is the major chemical constituent in the essential oil of numerous plant species. Several biological properties have been described for this molecule, including modulation of enzymatic targets relevant for the inflammatory response, such as 5-lipoxygenase (5-LOX). As so, there is interest in expanding the chemical space of this molecule to develop new molecules to be used in inflammatory conditions. We describe the chemometric analysis of several eugenol derivatives, which show that the chemical space of the parent molecule was successfully expanded. All molecules were evaluated for their inhibition towards 5-LOX, an important player in inflammatory pathways. Four derivatives exhibited significant 5-LOX inhibitory activity, which prompted further studies. The most promising compounds, 4-allylbenzene-1,2-diol 2, ethyl-4-(4-allyl-2-methoxyphenoxy)butanoate 4e, 3-(2-methoxy-4-(oxiran-2-ylmethyl)phenoxy)propyl acetate 5d and 4-(3-(tert-butoxy)-2-hydroxypropyl)-2-methoxyphenol 7c, were submitted to in silico assays to validate their affinity and stability towards 5-LOX, which helped clarify the mechanism by which these molecules interact and inhibit this enzyme.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2535586"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12377105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956587","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

Inhibition of 12/15-LOX hyperactivation mitigates cognitive decline in a chronic cerebral hypoperfusion mouse model and in H₂O₂-induced HT22 cells: therapeutic effects of brozopine. 抑制12/15-LOX过度激活减轻慢性脑灌注不足小鼠模型和h2o2诱导的HT22细胞的认知能力下降：溴佐平的治疗作用

IF 5.4 2区医学

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2025-12-01 Epub Date: 2025-08-21 DOI: 10.1080/14756366.2025.2547259

Xuening Wang, Zhizai Lu, Qiuji Shao, Yi Wang, Zixin Zhang, Zhiyu Wang, Qingran Jia, Jinpeng Zhu, Yiran Song, Lingxu Yuan, Yiming Wang, Shaoyang Xu, Lirou He, Junbiao Chang, Yuan Gao

{"title":"Inhibition of 12/15-LOX hyperactivation mitigates cognitive decline in a chronic cerebral hypoperfusion mouse model and in H2O2-induced HT22 cells: therapeutic effects of brozopine.","authors":"Xuening Wang, Zhizai Lu, Qiuji Shao, Yi Wang, Zixin Zhang, Zhiyu Wang, Qingran Jia, Jinpeng Zhu, Yiran Song, Lingxu Yuan, Yiming Wang, Shaoyang Xu, Lirou He, Junbiao Chang, Yuan Gao","doi":"10.1080/14756366.2025.2547259","DOIUrl":"https://doi.org/10.1080/14756366.2025.2547259","url":null,"abstract":"Brozopine (BZP), a novel inhibitor of 12/15-lipoxygenase (12/15-LOX), has previously demonstrated efficacy in mitigating inflammatory and oxidative stress-related injury in cerebral ischaemia models. This study aimed to evaluate the therapeutic potential and underlying mechanisms of BZP in a mouse model of vascular dementia induced by chronic cerebral hypoperfusion. BZP was administered for 28 days following right unilateral common carotid artery occlusion (rUCCAO) in mice. BZP significantly alleviated cognitive impairment, behavioural deficits, and fine motor function. Mechanistically, BZP inhibited 12/15-LOX, cPLA2, p-p38 MAPK/p38 MAPK ratio, tumour necrosis factor-α, interlukin-1β, Aβ1-42 deposition, and Tau hyperphosphorylation in the brain and serum of rUCCAO mice. Similar protective effects were observed in both 12/15-LOX-overexpressed and H2O2-induced HT22 cell models. These findings suggest that BZP exerts its neuroprotective effects by targeting the 12/15-LOX/cPLA2/p38 MAPK pathway, offering a promising therapeutic strategy for mitigating the progression of cognitive impairment.","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"40 1","pages":"2547259"},"PeriodicalIF":5.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144956637","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

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

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 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