Molecular Diversity最新文献_第5页

Classification models and SAR analysis of anaplastic lymphoma kinase (ALK) inhibitors using machine learning algorithms with two data division methods. 使用两种数据分割方法的机器学习算法对无性淋巴瘤激酶 (ALK) 抑制剂进行分类模型和 SAR 分析。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-11-12 DOI: 10.1007/s11030-024-10990-x

Dan Qu, Aixia Yan

{"title":"Classification models and SAR analysis of anaplastic lymphoma kinase (ALK) inhibitors using machine learning algorithms with two data division methods.","authors":"Dan Qu, Aixia Yan","doi":"10.1007/s11030-024-10990-x","DOIUrl":"https://doi.org/10.1007/s11030-024-10990-x","url":null,"abstract":"Anaplastic lymphoma kinase (ALK) plays a critical role in the development of various cancers. In this study, the dataset of 1810 collected inhibitors were divided into a training set and a test set by the self-organizing map (SOM) and random method, respectively. We developed 32 classification models using Support Vector Machines (SVM), Decision Trees (DT), Random Forests (RF), and Extreme Gradient Boosting (XGBoost) to distinguish between highly and weakly active ALK inhibitors, with the inhibitors represented by MACCS and ECFP4 fingerprints. Model 7D which was built by the RF algorithm using training set 1/test set 1 divided by the SOM method, provided the best performance with a prediction accuracy of 90.97% and a Matthews correlation coefficient (MCC) value of 0.79 on the test set. We clustered the 1810 inhibitors into 10 subsets by K-Means algorithm to find out the structural characteristics of highly active ALK inhibitors. The main scaffolds of highly active ALK inhibitors were also analyzed based on ECFP4 fingerprints. It was found that some substructures have a significant effect on high activity, such as 2,4-diarylaminopyrimidine analogues, pyrrolo[2,1-f][1,2,4]triazin, indolo[2,3-b]quinoline-11-one, benzo[d]imidazol and pyrrolo[2,3-b]pyridine. In addition, the subsets were summarized into several clusters, among which four clusters showed a significant relationship with ALK inhibitory activity. Finally, Shapley additive explanations (SHAP) was also used to explain the influence of modeling features on model prediction results. The SHAP results indicated that our models can well reflect the structural features of ALK inhibitors.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Insight on novel sulfamoylphenyl pyrazole derivatives as anticancer carbonic anhydrase inhibitors. 新型氨基磺酰基苯基吡唑衍生物作为抗癌碳酸酐酶抑制剂的深入研究。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-11-11 DOI: 10.1007/s11030-024-11023-3

Rehab F Ahmed, Walaa R Mahmoud, Nagwa M Abdelgawad, Amany Belal, Reem I Alsantali, Mona F Said

{"title":"Insight on novel sulfamoylphenyl pyrazole derivatives as anticancer carbonic anhydrase inhibitors.","authors":"Rehab F Ahmed, Walaa R Mahmoud, Nagwa M Abdelgawad, Amany Belal, Reem I Alsantali, Mona F Said","doi":"10.1007/s11030-024-11023-3","DOIUrl":"https://doi.org/10.1007/s11030-024-11023-3","url":null,"abstract":"As another part continue for our previous study, variable substituted pyrazoles bearing sulfamoylphenyl moiety were synthesized and screened against two cancer related human carbonic anhydrase (hCA) isoforms and acetazolamide (AAZ) used as a reference standard. Some compounds as 4e and 6c manifested a promising inhibitory activity against both isoforms (KI = 0.072, 0.081 and 0.073, 0.095 µM), respectively. While others as 4a and 5e showed inhibitory activity against hCA IX only (KI = 0.062, 0.04 µM) or against hCA XII only as compound 5b (KI = 0.106 µM) compared to AAZ (KI = 0.065, 0.046 µM), respectively. Also, the anticancer efficacy against 60 cancer cell lines for the target compounds was assessed, and the most promising ones were 4d and 5a-d. Further investigation of the anticancer activity of 5b on MCF-7 cell line explored (IC50 = 5.21 µM) compared to doxorubicin (IC50 = 11.58 µM). Moreover, compound 5b was exposed to cell cycle analysis and apoptotic assay on MCF-7 breast cancer cell line under both normal and hypoxic conditions at its IC50 concentration with elevation of total apoptotic cells % in MCF-7 relative to the control cells; respectively. Finally, molecular modelling simulations rationalized the in vitro testing results.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Decarboxylative click cycloaddition: an emerging strategy towards substituted 1,2,3-triazole derivatives. 脱羧点击环化反应：实现取代的 1,2,3-三唑衍生物的新兴战略。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-11-10 DOI: 10.1007/s11030-024-11014-4

Manpreet Kaur, Divya Bharti, Vinod Kumar, Praveen Kumar Verma, Rakesh Kumar

引用次数: 0

Design, synthesis, and anti-breast cancer activity evaluation of novel 3-cyanopyridine derivatives as PIM-1 inhibitors. 作为 PIM-1 抑制剂的新型 3-氰基吡啶衍生物的设计、合成和抗乳腺癌活性评价。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-11-09 DOI: 10.1007/s11030-024-11010-8

Bahgat R M Hussein, Hayam H Mohammed, Eman A Ahmed, Omar Alshazly, Mamdouh F A Mohamed, Omran A Omran

{"title":"Design, synthesis, and anti-breast cancer activity evaluation of novel 3-cyanopyridine derivatives as PIM-1 inhibitors.","authors":"Bahgat R M Hussein, Hayam H Mohammed, Eman A Ahmed, Omar Alshazly, Mamdouh F A Mohamed, Omran A Omran","doi":"10.1007/s11030-024-11010-8","DOIUrl":"https://doi.org/10.1007/s11030-024-11010-8","url":null,"abstract":"A novel series of cyanopyridines 7a-j were synthesized via a one-pot multicomponent reaction of arylidene 4 with ammonium acetate 5 and respective methylaryl/heterylketones 6a-j in ethanol using vanillin as a natural starting material. Moreover, the regioselective alkylation reaction was studied by the treatment of cyanopyridines 7a-f and 7j with CH3I in the presence of K2CO3 in DMF to afford O-methylcyanopyridines 8a-g (major) and N-methylcyanopyridines 9a-g (minor), whereas bipyridine 7h gave bipyridinium iodide salt 10. All of the designed cyanopyridines were evaluated as anti-breast cancer (MCF-7) cell lines via PIM Kinase inhibitory activity, and the results displayed that some of them showed high activities, especially compounds 7h and 8f, which showed excellent activities against MCF-7 with IC50 values of 1.89 and 1.69 μM, respectively, more potent than the reference drug doxorubicin. Mechanistically, compounds 7h and 8f exhibited strong in vitro PIM-1 kinase inhibitory activity with an IC50 of 0.281 and 0.58 μM, respectively, compared to the reference staurosporine. Moreover, compound 7h arrested the tumor cells at the S phase and caused cell death mainly by inducing early and late apoptosis. Molecular docking studies against PIM-1 revealed good binding modes of the synthesized compound and showed agreement with the biological results.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Design, synthesis and evaluation of benzothiazole-derived phenyl thioacetamides as dual inhibitors of monoamine oxidases and cholinesterases. 设计、合成和评估作为单胺氧化酶和胆碱酯酶双重抑制剂的苯并噻唑衍生苯基硫代乙酰胺。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-11-09 DOI: 10.1007/s11030-024-11031-3

Sandeep Kumar, Rangan Mitra, Senthil Raja Ayyannan

{"title":"Design, synthesis and evaluation of benzothiazole-derived phenyl thioacetamides as dual inhibitors of monoamine oxidases and cholinesterases.","authors":"Sandeep Kumar, Rangan Mitra, Senthil Raja Ayyannan","doi":"10.1007/s11030-024-11031-3","DOIUrl":"https://doi.org/10.1007/s11030-024-11031-3","url":null,"abstract":"A series of rationally designed benzothiazole-derived thioacetamides was synthesized and investigated for monoamine oxidases (MAO-A and MAO-B) and cholinesterases (AChE and BChE) inhibition properties. The tested compounds 18-31 inhibited MAO-A and MAO-B in the micromolar to nanomolar range and AChE in the submicromolar range. Compound 28 was identified as the most potent MAO-A inhibitor with an IC50 = 0.030 ± 0.008 µM, whereas compound 30 showed the highest potency towards MAO-B and AChE with IC50 values of 0.015 ± 0.007 µM and 0.114 ± 0.003 µM, respectively. Further, compound 30 inhibited BChE at an IC50 value of 4.125 ± 0.143 µM. Among all screened molecules, compound 30 emerged as the lead dual MAO-B and AChE inhibitor that blocked these enzymes in a competitive-reversible and mixed-reversible mode, respectively. Selected compounds have displayed iron-chelation and antioxidant properties. Further, computational assessment of ligand binding affinity and pharmacokinetic parameters of all new compounds and molecular dynamic simulation of compound 30 with MAO-B and AChE were carried out to understand ligand efficiency, pharmacokinetic, and virtual molecular interaction profile, respectively. The in silico ADMET prediction studies revealed a few undesired pharmacokinetic attributes of our compounds. The attempted virtual lead-based library synthesis and subsequent biological investigation produced a new benzothiazole-bearing dual MAO-B and AChE inhibitor as a prospective MTDL candidate for treating neurological disorders.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structure-based design and synthesis of novel FXIa inhibitors targeting the S2' subsite for enhanced antithrombotic efficacy. 基于结构设计和合成以 S2'位点为靶点的新型 FXIa 抑制剂，提高抗血栓疗效。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-11-08 DOI: 10.1007/s11030-024-11024-2

Jie Wu, Hao Yue, Xiaoqian Wang, Yaning Yao, Nan Du, Ping Gong

{"title":"Structure-based design and synthesis of novel FXIa inhibitors targeting the S2' subsite for enhanced antithrombotic efficacy.","authors":"Jie Wu, Hao Yue, Xiaoqian Wang, Yaning Yao, Nan Du, Ping Gong","doi":"10.1007/s11030-024-11024-2","DOIUrl":"https://doi.org/10.1007/s11030-024-11024-2","url":null,"abstract":"Factor XIa (FXIa), a key component of the intrinsic coagulation pathway, has recently been recognized as a safe and effective target for antithrombotic therapy. Research indicates that FXIa inhibitors can lower bleeding risk compared to novel oral anticoagulants. In this study, we designed and synthesized a series of novel FXIa inhibitors based on the structure of Asundexian, with a particular focus on optimizing the P2' region to enhance binding to the S2' subsite of FXIa. This strategy led to the discovery of compound F47, which demonstrated significantly greater FXIa inhibition (IC50 = 2.0 nM) compared to Asundexian (IC50 = 5.0 nM). F47 also showed excellent anticoagulant activity in the aPTT assay (EC2x = 0.4 μM), with strong efficacy and minimal impact on the extrinsic coagulation pathway. Additionally, F47 exhibited inhibitory activity against plasma kallikrein (PKal), with selectivity comparable to that of Asundexian. The compound also displayed acceptable stability in human liver microsomal stability assays. Molecular modeling revealed that F47 binds tightly to the S1, S1', and S2' pockets of FXIa while maintaining key interactions; notably, its P2' moiety forms two additional π-π stacking interactions with the crucial amino acid TYR143. Further studies demonstrated that F47 exhibits dose-dependent antithrombotic efficacy in a rat FeCl3-induced thrombosis model. Ongoing research aims to further elucidate the potential of compound F47 as a promising lead in antithrombotic therapy.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immunoinformatics investigation on pathogenic Escherichia coli proteome to develop an epitope-based peptide vaccine candidate. 对致病性大肠杆菌蛋白质组进行免疫信息学研究，以开发基于表位的多肽候选疫苗。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-11-08 DOI: 10.1007/s11030-024-11034-0

Soham Chowdhury, Pinkan Sadhukhan, Nibedita Mahata

{"title":"Immunoinformatics investigation on pathogenic Escherichia coli proteome to develop an epitope-based peptide vaccine candidate.","authors":"Soham Chowdhury, Pinkan Sadhukhan, Nibedita Mahata","doi":"10.1007/s11030-024-11034-0","DOIUrl":"https://doi.org/10.1007/s11030-024-11034-0","url":null,"abstract":"Escherichia coli (E. coli), a gram-negative bacterium, quickly colonizes in the human gastrointestinal tract after birth and typically sustains a long-term, symbiotic relationship with the host. However, certain virulent strains of E. coli can cause diseases such as urinary tract infections, meningitis, and enteric disorders. The rising antibiotic resistance among these strains has heightened the urgency for an effective vaccine. This study employs immunoinformatics and a reverse vaccinology technique to identify prospective antigens and create an efficient vaccine construct. In this study, we reported the \"Attaching and Effacing Protein\" a novel outer-membrane protein conserved in all pathogenic E. coli strains, based on proteome screening. We developed an in silico multi-epitope vaccine that includes helper T lymphocyte (HTL), cytotoxic T lymphocyte (CTL), B cell lymphocyte (BCL), and pan HLA DR-binding reactive epitope (PADRE) sequences, along with appropriate linkers and adjuvants. Machine Learning algorithms were used to evaluate antigenicity, solubility, stability, and non-allergenicity of the vaccine construct. Additionally, molecular docking analysis revealed that vaccine construct has a strong predicted binding affinity for human toll-like receptors on the cell surface. In this context, laboratory validations are necessary to demonstrate the effectiveness of the possible vaccine design that showed encouraging findings through computational validation.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phytosterols as inhibitors of New Delhi metallo-β-lactamase (NDM-1): an in silico study. 植物甾醇作为新德里金属-β-内酰胺酶（NDM-1）的抑制剂：一项硅学研究。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-11-08 DOI: 10.1007/s11030-024-11020-6

Mashihur Rahman, Mohd Ahsan, Md Tabish Rehman, Mohamed F AlAjmi, Md Khurshid Alam Khan

{"title":"Phytosterols as inhibitors of New Delhi metallo-β-lactamase (NDM-1): an in silico study.","authors":"Mashihur Rahman, Mohd Ahsan, Md Tabish Rehman, Mohamed F AlAjmi, Md Khurshid Alam Khan","doi":"10.1007/s11030-024-11020-6","DOIUrl":"https://doi.org/10.1007/s11030-024-11020-6","url":null,"abstract":"The global emergence of New Delhi metallo-β-lactamase-1 (NDM-1) poses a formidable challenge to antibiotic therapy, as it confers resistance to a wide range of β-lactam antibiotics. This study aims to identify potential inhibitors of NDM-1 and thereby restore the effectiveness of the current antibiotics. Employing a comprehensive computational approach integrating molecular docking and molecular dynamics (MD) simulations, a library of phytosterols was screened to identify promising candidates for inhibiting NDM-1 activity. Using the binding energy of meropenem, a frontline carbapenem antibiotic, as a reference, avenasterol, brassicasterol, and stigmasterol emerged as top phytosterol candidates for further investigation. Subsequent MD simulations confirmed the stability of NDM-1 complexes with avenasterol and stigmasterol over the simulation period, indicating their potential efficacy. These findings suggest that avenasterol and stigmasterol may effectively inhibit NDM-1 activity, warranting validation through in vitro and in vivo studies. Furthermore, these phytosterols hold promise as lead compounds for developing novel NDM-1 inhibitors. Their natural origin and potential inhibitory activity against NDM-1 offer compelling avenues for developing alternative antibacterial therapies to combat multidrug-resistant infections. This study underscores the utility of computational methods in drug discovery and highlights the potential of phytosterols as valuable candidates for addressing antibiotic resistance.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Studies on the synthesis, crystal structures, biological activities and molecular docking of novel natural methylxanthine derivatives containing piperazine moiety. 研究含有哌嗪分子的新型天然甲基黄嘌呤衍生物的合成、晶体结构、生物活性和分子对接。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-11-07 DOI: 10.1007/s11030-024-10972-z

Wenqi Fan, Shuyun Zhang, Na Yang, Yonghong Li, Xiao Zhang, Congwei Niu, Xinghai Liu, Baolei Wang

{"title":"Studies on the synthesis, crystal structures, biological activities and molecular docking of novel natural methylxanthine derivatives containing piperazine moiety.","authors":"Wenqi Fan, Shuyun Zhang, Na Yang, Yonghong Li, Xiao Zhang, Congwei Niu, Xinghai Liu, Baolei Wang","doi":"10.1007/s11030-024-10972-z","DOIUrl":"https://doi.org/10.1007/s11030-024-10972-z","url":null,"abstract":"A series of novel methylxanthine Mannich base derivatives containing substituted piperazine groups were synthesized through Mannich reaction. The structures of these new compounds were confirmed by NMR, HRMS or elemental analyses, and X-ray single crystal diffraction. Bioassay results showed that some of the compounds exhibit favorable fungicidal and insecticidal potentials. Particularly, compounds IIk, IIq, IIs and compounds If, IIk against Physalospora piricola and Rhizoctonia cerealis, respectively, were comparable with Azoxystrobin and Chlorothalonil; compound Ik exhibited higher potency than Triflumuron against Plutella xylostella L., suggesting its potential as a lead compound for further development in insecticidal applications. Despite possessing weak herbicidal activities, the target compounds, especially the methylxanthine S-Mannich base derivatives I displayed remarkable inhibitory activities toward ketol-acid reductoisomerase (KARI); compounds Ib, If, and Ik which had Ki values of 2.41-8.08 µmol/L can be novel potent KARI inhibitors for deeper exploration. The SARs were analyzed in detail. The molecular docking studies on the highly active inhibitors with KARI provided possible binding modes between inhibitor and the target enzyme. The physicochemical parameter predictions indicated that compounds Ik, IIk, IIq and IIs have \"druglike structure\" features. The research results in this article may bring a new inspiration to the extensive explorations on new methylxanthine derivatives in pesticide area.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring bacterial metabolites in microbe-human host dialogue and their therapeutic potential in Alzheimer's diseases. 探索微生物与人类宿主对话中的细菌代谢物及其对阿尔茨海默病的治疗潜力。

IF 3.9 2区化学

Molecular Diversity Pub Date : 2024-11-05 DOI: 10.1007/s11030-024-11028-y

Sarangthem Dinamani Singh, Pankaj Bharali, Selvaraman Nagamani

{"title":"Exploring bacterial metabolites in microbe-human host dialogue and their therapeutic potential in Alzheimer's diseases.","authors":"Sarangthem Dinamani Singh, Pankaj Bharali, Selvaraman Nagamani","doi":"10.1007/s11030-024-11028-y","DOIUrl":"https://doi.org/10.1007/s11030-024-11028-y","url":null,"abstract":"Neurological dysfunction in association with aging, dementia, and cognitive impairment is the major cause of Alzheimer's disease (AD). Current AD therapies often yield unsatisfactory results due to their poor mechanism in treating the underlying mechanism of the disease. Recent studies suggested that metabolites from the gut microbiota facilitate brain-gut communication. A systematic network pharmacology study and the structure- and analog-based approaches are employed to investigate the metabolites produced by gut microbiota to treat AD. The microbiota metabolites available in the gutMGene database were considered in this study. Two servers, namely Swiss Target Prediction (STP) and Similarity Ensemble Approach (SEA), were used to identify the possible AD targets for the selected metabolites. Detailed KEGG pathway and Gene Ontology (GO) analysis on identified hub genes highlighted the importance of IL6, AKT1, and GSK3B in AD pathophysiology. MMTSp (Microbiota Metabolites Target Signaling pathways) network analysis elucidated that there is a strong relationship with microbiota (Paraprevotella xylaniphila YIT 11841, Bifidobacterium dentium, Paraprevotella clara YIT 11840, Enterococcus sp. 45, Bacteroides sp. 45, Bacillus sp. 46, Escherichia sp. 33, Enterococcus casseliflavus, Bacteroides uniformis, Alistipes indistinctus YIT 12060, Bacteroides ovatus, Escherichia sp. 12, and Odoribacter laneus YIT 12061) and AD pathogenesis. In addition to this, we performed molecular docking to study the metabolite interactions in the AD drug targets. The ADME/T properties of these metabolites were also calculated and the results are discussed in detail.","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0