Journal of Enzyme Inhibition and Medicinal Chemistry最新文献

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Anilino-1,4-naphthoquinones as potent mushroom tyrosinase inhibitors: in vitro and in silico studies. 作为强效蘑菇酪氨酸酶抑制剂的苯胺基-1,4-萘醌类化合物:体外和硅学研究。
IF 5.6 2区 医学
Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-05-30 DOI: 10.1080/14756366.2024.2357174
Sahachai Sabuakham, Sutita Nasoontorn, Napat Kongtaworn, Thanyada Rungrotmongkol, Atit Silsirivanit, Ratchanok Pingaew, Panupong Mahalapbutr
{"title":"Anilino-1,4-naphthoquinones as potent mushroom tyrosinase inhibitors: <i>in vitro</i> and <i>in silico</i> studies.","authors":"Sahachai Sabuakham, Sutita Nasoontorn, Napat Kongtaworn, Thanyada Rungrotmongkol, Atit Silsirivanit, Ratchanok Pingaew, Panupong Mahalapbutr","doi":"10.1080/14756366.2024.2357174","DOIUrl":"10.1080/14756366.2024.2357174","url":null,"abstract":"<p><p>Tyrosinase, a pivotal enzyme in melanin synthesis, is a primary target for the development of depigmenting agents. In this work, <i>in vitro</i> and <i>in silico</i> techniques were employed to identify novel tyrosinase inhibitors from a set of 12 anilino-1,4-naphthoquinone derivatives. Results from the mushroom tyrosinase activity assay indicated that, among the 12 derivatives, three compounds (<b>1</b>, <b>5</b>, and <b>10</b>) demonstrated the most significant inhibitory activity against mushroom tyrosinase, surpassing the effectiveness of the kojic acid. Molecular docking revealed that all studied derivatives interacted with copper ions and amino acid residues at the enzyme active site. Molecular dynamics simulations provided insights into the stability of enzyme-inhibitor complexes, in which compounds <b>1</b>, <b>5</b>, and particularly <b>10</b> displayed greater stability, atomic contacts, and structural compactness than kojic acid. Drug likeness prediction further strengthens the potential of anilino-1,4-naphthoquinones as promising candidates for the development of novel tyrosinase inhibitors for the treatment of hyperpigmentation disorders.</p>","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2357174"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11141316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174642","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
Discovery of novel 2,4-diarylaminopyrimidine hydrazone derivatives as potent anti-thyroid cancer agents capable of inhibiting FAK. 发现新型 2,4-二芳基氨基嘧啶腙衍生物,作为能够抑制 FAK 的强效抗甲状腺癌药物。
IF 5.6 2区 医学
Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-11-19 DOI: 10.1080/14756366.2024.2423875
Hongting Li, Mei-Qi Jia, Zhao-Long Qin, Changliang Lu, Weili Chu, Ze Zhang, Jinbo Niu, Jian Song, Sai-Yang Zhang, Lijun Fu
{"title":"Discovery of novel 2,4-diarylaminopyrimidine hydrazone derivatives as potent anti-thyroid cancer agents capable of inhibiting FAK.","authors":"Hongting Li, Mei-Qi Jia, Zhao-Long Qin, Changliang Lu, Weili Chu, Ze Zhang, Jinbo Niu, Jian Song, Sai-Yang Zhang, Lijun Fu","doi":"10.1080/14756366.2024.2423875","DOIUrl":"10.1080/14756366.2024.2423875","url":null,"abstract":"<p><p>In this work, thirty 2,4-diarylaminopyrimidine-based hydrazones were designed, synthesised, and their anti-thyroid cancer activity were explored. The majority of compounds exhibit moderate to excellent cytotoxic activity against FAK overexpressing TPC-1 cells, with IC<sub>50</sub> values ranging from 0.113 to 1.460 μM. Among them, compound <b>14f</b> displayed exceptional anti-proliferative effect against TPC-1 cells (IC<sub>50</sub> = 0.113 μM) and potent FAK inhibitory potency (IC<sub>50</sub> = 35 nM). In <i>silico</i> studies indicated that compound <b>14f</b> could well bind to FAK (Focal Adhesion Kinase) and have favourable pharmacokinetic profiles. In addition, compound <b>14f</b> could inhibit the phosphorylation of FAK at Tyr397, Tyr576/577 and Tyr925, and did not affect the expression level of FAK in TPC-1 cells. Compound <b>14f</b> was also effective in inhibiting the proliferation and migration of thyroid cancer cells TPC-1. Thus, these novel 4-arylaminopyrimidine hydrazone derivatives exhibited potent anti-thyroid cancer activities through the inhibition of FAK.</p>","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2423875"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668088","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
Evaluation of hydrazone and N-acylhydrazone derivatives of vitamin B6 and pyridine-4-carbaldehyde as potential drugs against Alzheimer's disease.
IF 5.6 2区 医学
Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-12-09 DOI: 10.1080/14756366.2024.2431832
Marija Bartolić, Ana Matošević, Nikola Maraković, Valentina Bušić, Sunčica Roca, Dražen Vikić-Topić, Antonio Sabljić, Anita Bosak, Dajana Gašo-Sokač
{"title":"Evaluation of hydrazone and <i>N</i>-acylhydrazone derivatives of vitamin B6 and pyridine-4-carbaldehyde as potential drugs against Alzheimer's disease.","authors":"Marija Bartolić, Ana Matošević, Nikola Maraković, Valentina Bušić, Sunčica Roca, Dražen Vikić-Topić, Antonio Sabljić, Anita Bosak, Dajana Gašo-Sokač","doi":"10.1080/14756366.2024.2431832","DOIUrl":"10.1080/14756366.2024.2431832","url":null,"abstract":"<p><p>The growing prevalence of Alzheimer's disease calls for a drug that can simultaneously act towards several targets involved in the pathophysiology of the disease. In our study, we evaluated the potential of hydrazone and <i>N</i>-acylhydrazone derivatives of vitamin B6 and pyridine-4-carbaldehyde to be used as multi-target directed ligands targeting cholinergic system by inhibiting acetyl- and butyrylcholinesterase, lowering the accumulation of β-amyloid plaques by inhibiting both the β-secretase activity and amyloid self-aggregation, and maintaining the biometal balance by chelating certain biometals. Our results showed that all of the tested hydrazones were potent inhibitors of human cholinesterases with inhibition constants (<i>K</i>i) in micromolar range able to lower the activity of β-secretase, inhibit amyloid aggregation, chelate biometals and act as antioxidants. Also, most of them were estimated to be able to cross the blood-brain barrier by passive transport and to be absorbed in human intestines as well as with moderate metabolic stability in liver microsomes.</p>","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2431832"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801083","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
Expanding the inhibitor space of the WWP1 and WWP2 HECT E3 ligases. 拓展 WWP1 和 WWP2 HECT E3 连接酶的抑制剂空间。
IF 5.6 2区 医学
Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-09-02 DOI: 10.1080/14756366.2024.2394895
Ashley P Dudey, Jake M Rigby, Gregory R Hughes, G Richard Stephenson, Thomas E Storr, Andrew Chantry, Andrew M Hemmings
{"title":"Expanding the inhibitor space of the WWP1 and WWP2 HECT E3 ligases.","authors":"Ashley P Dudey, Jake M Rigby, Gregory R Hughes, G Richard Stephenson, Thomas E Storr, Andrew Chantry, Andrew M Hemmings","doi":"10.1080/14756366.2024.2394895","DOIUrl":"10.1080/14756366.2024.2394895","url":null,"abstract":"<p><p>The HECT E3 ubiquitin ligases 1 (WWP1) and 2 (WWP2) are responsible for the ubiquitin-mediated degradation of key tumour suppressor proteins and are dysregulated in various cancers and diseases. Here we expand their limited inhibitor space by identification of NSC-217913 displaying a WWP1 IC<sub>50</sub> of 158.3 µM (95% CI = 128.7, 195.1 µM). A structure-activity relationship by synthesis approach aided by molecular docking led to compound <b>11</b> which displayed increased potency with an IC<sub>50</sub> of 32.7 µM (95% CI = 24.6, 44.3 µM) for WWP1 and 269.2 µM (95% CI = 209.4, 347.9 µM) for WWP2. Molecular docking yielded active site-bound poses suggesting that the heterocyclic imidazo[4,5-<i>b</i>]pyrazine scaffold undertakes a π-stacking interaction with the phenolic group of tyrosine, and the ethyl ester enables strong ion-dipole interactions. Given the therapeutic potential of WWP1 and WWP2, we propose that compound 11 may provide a basis for future lead compound development.</p>","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2394895"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119988","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, molecular modelling, and biological evaluation of novel quinoxaline derivatives for treating type II diabetes. 用于治疗 II 型糖尿病的新型喹喔啉衍生物的合成、分子建模和生物学评价。
IF 5.6 2区 医学
Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-09-23 DOI: 10.1080/14756366.2024.2395985
Fatmah Ali S Alasmary, Dalal A Abdullah, Vijay H Masand, Abir Ben Bacha, Abdelsattar Mansour Omar Ebeid, Moustafa E El-Araby, Ahmed M Alafeefy
{"title":"Synthesis, molecular modelling, and biological evaluation of novel quinoxaline derivatives for treating type II diabetes.","authors":"Fatmah Ali S Alasmary, Dalal A Abdullah, Vijay H Masand, Abir Ben Bacha, Abdelsattar Mansour Omar Ebeid, Moustafa E El-Araby, Ahmed M Alafeefy","doi":"10.1080/14756366.2024.2395985","DOIUrl":"10.1080/14756366.2024.2395985","url":null,"abstract":"<p><p>Quinoxalines are benzopyrazine derivatives with significant therapeutic impact in the pharmaceutical industry. They proved to be useful against inflammation, bacterial, fungal, viral infection, diabetes and other applications. Very recently, in January 2024, the FDA approved new quinoxaline containing drug, erdafitinib for treatment of certain carcinomas. Despite the diverse biological activities exhibited by quinoxaline derivatives and the role of secretory phospholipase A2 (sPLA2) in diabetes-related complications, the potential of sPLA2-targeting quinoxaline-based inhibitors to effectively address these complications remains unexplored. Therefore, we designed novel sPLA2- and α-glucosidase-targeting quinoxaline-based heterocyclic inhibitors to regulate elevated post-prandial blood glucose linked to patients with diabetes-related cardiovascular complications. Compounds <b>5a-d</b> and <b>6a-d</b> were synthesised by condensing quinoxaline hydrazides with various aryl sulphonyl chlorides. Biological screening revealed compound <b>6a</b> as a potent sPLA2 inhibitor (IC<sub>50</sub> = 0.0475 µM), whereas compound <b>6c</b> most effectively inhibited α-glucosidase (IC<sub>50</sub> = 0.0953 µM), outperforming the positive control acarbose. Moreover, compound <b>6a</b> was the best inhibitor for both enzymes. Molecular docking revealed pharmacophoric features, highlighting the importance of a sulfonohydrazide moiety in the structural design of these compounds, leading to the development of potent sPLA2 and α-glucosidase inhibitors. Collectively, our findings helped identify promising candidates for developing novel therapeutic agents for treating diabetes mellitus.</p>","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2395985"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11421147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142288899","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 activity evaluation of dihydromyricetin derivatives against SARS-CoV-2-Omicron virus. 针对 SARS-CoV-2-Omicron 病毒的二氢杨梅素衍生物的设计、合成和生物活性评价。
IF 5.6 2区 医学
Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-08-29 DOI: 10.1080/14756366.2024.2390909
Cong Wu, Qi Jiang, Hui Zhong, Xudong Zhou, Leping Liu, Tong Pan, Chao Liu, Wei Wang, Wenbing Sheng
{"title":"Design, synthesis, and biological activity evaluation of dihydromyricetin derivatives against SARS-CoV-2-Omicron virus.","authors":"Cong Wu, Qi Jiang, Hui Zhong, Xudong Zhou, Leping Liu, Tong Pan, Chao Liu, Wei Wang, Wenbing Sheng","doi":"10.1080/14756366.2024.2390909","DOIUrl":"https://doi.org/10.1080/14756366.2024.2390909","url":null,"abstract":"<p><p>An oxidising and substituting one-pot reaction strategy has been developed to synthesise dihydromyricetin derivatives with the aim of enhancing the inhibitory activity of dihydromyricetin against SARS-CoV-2. Different <i>ω</i>-methoxy-<i>ω</i>-oxeylkyl was introduced in C<sub>7</sub>-OH site and yielded eight analogs, all of them showed good inhibitory activity against SARS-CoV-2 3CL<sup>pro</sup> with IC<sub>50</sub> values ranging from 0.72 to 2.36 μM. In the Vero E6-cell, compound <b>3</b> has a good activity of anti-SARS-CoV-2 virus (Omicron virus BA.5) in the prevention model, with an EC<sub>50</sub> of 15.84 μM, and so do compound <b>10</b> in the therapeutic model, with an EC<sub>50</sub> of 11.52 μM. The results suggest that the introduction of long chain <i>ω</i>-oxeylkyl at C<sub>7</sub>-OH facilitate the inhibition of viral replication in the therapeutic model, which is consistent with the binding energies predicted from molecular docking conclusions. It implies that dihydromyricetin derivatives have the potential to become effective inhibitors of SARS-CoV-2 Omicron and other viruses.</p>","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2390909"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11363738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108024","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
Exploring structural and biological insights of TEAD through rational design and synthesis of niflumic acid derivatives. 通过合理设计和合成硝氟酸衍生物,探索 TEAD 的结构和生物学特性。
IF 5.6 2区 医学
Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-11-04 DOI: 10.1080/14756366.2024.2419925
Yong-Sung Choi, Yoon-Jung Kim, Yeram Jeon, Jong Soon Kang, Juhee Lee, Eunmi Hong, Young-Hoon Park, Wantae Kim, Boksik Cha, Raok Jeon
{"title":"Exploring structural and biological insights of TEAD through rational design and synthesis of niflumic acid derivatives.","authors":"Yong-Sung Choi, Yoon-Jung Kim, Yeram Jeon, Jong Soon Kang, Juhee Lee, Eunmi Hong, Young-Hoon Park, Wantae Kim, Boksik Cha, Raok Jeon","doi":"10.1080/14756366.2024.2419925","DOIUrl":"10.1080/14756366.2024.2419925","url":null,"abstract":"<p><p>Transcriptional enhanced associate domain (TEAD) transcription factors undergo auto-palmitoylation, which is critical to mediate their function and maintain stability. Targeting the palmitate binding pocket of TEAD holds considerable promise for drug discovery, and it can be characterised into three components: a conserved cysteine, a hydrophobic main pocket, and a hydrophilic side pocket. Endogenous palmitate and several known TEAD inhibitors interact with the cysteine and hydrophobic residues in the deep hydrophobic pocket. We anticipate that precise targeting of the polar side pocket could facilitate the discovery of inhibitors with enhanced potencies and properties. Herein, we selected niflumic acid as the core scaffold suitable for targeting the three characteristic components of TEAD palmitate pocket. Reversible and irreversible compounds with substituents capable of directing each part of the palmitate pocket were designed. The newly synthesised compounds inhibited the palmitoylation and transcriptional activity of TEAD and elicited growth-inhibitory effects against several carcinomas, including mesothelioma.</p>","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2419925"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568641","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
Computational fragment-based drug design of potential Glo-I inhibitors. 基于计算片段的潜在 Glo-I 抑制剂药物设计。
IF 5.6 2区 医学
Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-01-22 DOI: 10.1080/14756366.2024.2301758
Roaa S Bibars, Qosay A Al-Balas
{"title":"Computational fragment-based drug design of potential Glo-I inhibitors.","authors":"Roaa S Bibars, Qosay A Al-Balas","doi":"10.1080/14756366.2024.2301758","DOIUrl":"10.1080/14756366.2024.2301758","url":null,"abstract":"<p><p>In this study, a fragment-based drug design approach, particularly <i>de novo</i> drug design, was implemented utilising three different crystal structures in order to discover new privileged scaffolds against glyoxalase-I enzyme as anticancer agents. The fragments were evoluted to indicate potential inhibitors with high receptor affinities. The resulting compounds were served as a benchmark for choosing similar compounds from the ASINEX® database by applying different computational ligand-based drug design techniques. Afterwards, the selection of potential hits was further aided by various structure-based approaches. Then, 14 compounds were purchased, and tested <i>in vitro</i> against Glo-I enzyme. Of the tested 14 hits, the biological screening results showed humble activities where the percentage of Glo-I inhibition ranged from 0-18.70 %. Compound <b>19</b> and compound <b>28</b>, whose percentage of inhibitions are 18.70 and 15.80%, respectively, can be considered as hits that need further optimisation in order to be converted into lead-like compounds.</p>","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2301758"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10810659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139512636","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 potential inhibitors against Staphylococcus aureus shikimate dehydrogenase through virtual screening and susceptibility test. 通过虚拟筛选和药敏试验鉴定金黄色葡萄球菌莽草酸脱氢酶的潜在抑制剂。
IF 5.6 2区 医学
Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-01-17 DOI: 10.1080/14756366.2024.2301768
Mengfan Zhu, Jinfeng Qu, Qi Deng
{"title":"Identification of potential inhibitors against <i>Staphylococcus aureus</i> shikimate dehydrogenase through virtual screening and susceptibility test.","authors":"Mengfan Zhu, Jinfeng Qu, Qi Deng","doi":"10.1080/14756366.2024.2301768","DOIUrl":"10.1080/14756366.2024.2301768","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> shikimate dehydrogenase (SaSDH) plays a crucial role in the growth of <i>Staphylococcus aureus</i> (<i>S. aureus</i>), but absent in mammals and therefore a potential target for antibacterial drugs to treat drug-resistant <i>S. aureus</i> infection. In this study, a 3D model of SaSDH was constructed by homology modelling and inhibitors of SaSDH were screened through virtual screening. (-)-Gallocatechin gallate and rhodiosin were identified as inhibitors with K<sub>i</sub>s of 2.47 μM and 73.38 μM, respectively. Molecular docking and isothermal titration calorimetry showed that both inhibitors interact with SaSDH with a K<sub>D</sub> of 44.65 μM for (-)-gallocatechin gallate and 16.45 μM for rhodiosin. Both inhibitors had antibacterial activity, showing MICs of 50 μg/mL for (-)-gallocatechin gallate and 250 μg/mL for rhodiosin against <i>S. aureus</i>. The current findings have the potential for identification of drugs to treat <i>S. aureus</i> infections by targeting SaSDH.</p>","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2301768"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10798293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485389","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 comprehensive investigation of the anion inhibition profile of a β-carbonic anhydrase from Acinetobacter baumannii for crafting innovative antimicrobial treatments. 全面研究鲍曼不动杆菌β-碳酸酐酶的阴离子抑制谱,以开发创新的抗菌疗法。
IF 5.6 2区 医学
Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2024-07-16 DOI: 10.1080/14756366.2024.2372731
Viviana De Luca, Simone Giovannuzzi, Claudiu T Supuran, Clemente Capasso
{"title":"A comprehensive investigation of the anion inhibition profile of a β-carbonic anhydrase from <i>Acinetobacter baumannii</i> for crafting innovative antimicrobial treatments.","authors":"Viviana De Luca, Simone Giovannuzzi, Claudiu T Supuran, Clemente Capasso","doi":"10.1080/14756366.2024.2372731","DOIUrl":"10.1080/14756366.2024.2372731","url":null,"abstract":"<p><p>This study refers to the intricate world of <i>Acinetobacter baumannii</i>, a resilient pathogenic bacterium notorious for its propensity at antibiotic resistance in nosocomial infections. Expanding upon previous findings that emphasised the bifunctional enzyme PaaY, revealing unexpected γ-carbonic anhydrase (CA) activity, our research focuses on a different class of CA identified within the <i>A. baumannii</i> genome, the β-CA, designated as 𝛽-AbauCA (also indicated as CanB), which plays a crucial role in the resistance mechanism mediated by AmpC beta-lactamase. Here, we cloned, expressed, and purified the recombinant 𝛽-AbauCA, unveiling its distinctive kinetic properties and inhibition profile with inorganic anions (classical CA inhibitors). The exploration of 𝛽-AbauCA not only enhances our understanding of the CA repertoire of <i>A. baumannii</i> but also establishes a foundation for targeted therapeutic interventions against this resilient pathogen, promising advancements in combating its adaptability and antibiotic resistance.</p>","PeriodicalId":15769,"journal":{"name":"Journal of Enzyme Inhibition and Medicinal Chemistry","volume":"39 1","pages":"2372731"},"PeriodicalIF":5.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC467105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620102","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
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