Current computer-aided drug design最新文献

{"title":"Computational Evaluation of Punica granatum Leaf Phytochemicals against Multi-drug Resistant E. coli: Molecular Docking, ADMET, MD Simulation, and DFT Studies.","authors":"Shivam Mishra, Shristi Modanwal, Prabhat Kumar, Ashutosh Mishra, Nidhi Mishra","doi":"10.2174/0115734099343126241105102839","DOIUrl":"https://doi.org/10.2174/0115734099343126241105102839","url":null,"abstract":"<p><strong>Introduction: </strong>Multidrug-resistant (MDR) E. coli presents a significant challenge in clinical settings, necessitating the exploration of novel therapeutic agents. Phytochemicals from Punica granatum (pomegranate) leaves have shown potential antibacterial properties. This study aims to identify and evaluate the efficacy of these phytochemicals against MDR E. coli.</p><p><strong>Objectives: </strong>This study aims to identify and evaluate the efficacy of most potential phytochemical of Punica granatum leaf against MDR E. coli. through molecular docking, adme, toxicity, molecular dynamic simulation, MMPBSA and DFT approaches.</p><p><strong>Methods: </strong>We performed molecular docking of 11 phytochemicals from the IMPPAT database with four MDR E. coli targets: 1AJ6, 1FJ8, 4BJP, and 6BU3. Granatin B demonstrated the best binding affinity and was further analyzed. ADME (Absorption, Distribution, Metabolism, and Excretion) and toxicity analyses were conducted to assess its pharmacokinetic properties and safety profile. Molecular Dynamics (MD) simulations were performed to evaluate the stability of Granatin B with the targets. Finally, density functional theory (DFT) analysis was carried out to understand the electronic properties and reactivity of Granatin B.</p><p><strong>Results: </strong>Granatin B exhibited the highest binding affinity among the 11 phytochemicals, indicating strong potential as an inhibitor of MDR E. coli. ADME analysis revealed favorable pharmacokinetic properties and toxicity analysis confirmed that Granatin B is non-toxic. MD simulations showed stable interactions between Granatin B and all four targets. DFT analysis provided insights into the electronic properties and reactive sites of Granatin B, supporting its potential mechanism of action.</p><p><strong>Conclusion: </strong>Granatin B from Punica granatum leaves is a promising candidate for treating MDR E. coli infections. The integration of molecular docking, ADME, toxicity, MD simulations, and DFT analysis underscores its therapeutic potential and paves the way for further experimental validation and development as a novel antibacterial agent.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a ceRNA Network Regulating Malignant Transformation of Isocitrate Dehydrogenase Mutant Astrocytoma: An Integrated Bioinformatics Study.","authors":"Yaqian Cui, Hongquan Zheng, Zhengwei Zhou, Suo Liu, Mingxue Shen, Runze Qiu, Xiong Zhang, Yingbin Li, Hongwei Fan","doi":"10.2174/0115734099293010240810181446","DOIUrl":"https://doi.org/10.2174/0115734099293010240810181446","url":null,"abstract":"<p><strong>Introduction: </strong>Astrocytoma is the most common glioma, accounting for about 65% of glioblastoma. Its malignant transformation is also one of the important causes of patient mortality, making it the most prevalent and difficult to treat in primary brain tumours. However, little is known about the underlying mechanisms of this transformation.</p><p><strong>Methods: </strong>In this study, we established a ceRNA network to screen out the potential regulatory pathways involved in the malignant transformation of IDH-mutant astrocytomas. Firstly, the Chinese Glioma Genome Atlas (CGGA) was employed to compare the expression levels of the differential expressed genes (DEGs) in astrocytomas. Then, the ceRNA-regulated network was constructed based on the interaction of lncRNA-miRNA-mRNA. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to explore the main functions of the differentially expressed genes. COX regression analysis and log-rank test were combined to screen the ceRNA network further. In addition, quantitative real-time PCR (qRT-PCR) was conducted to identify the potential regulatory mechanisms of malignant transformation in IDH-mutant astrocytoma. We constructed a ceRNA network with 34 lncRNAs, 29 miRNAs, and 71 mRNAs.</p><p><strong>Results: </strong>GO and KEGG analyses results suggested that DEGs were associated with tumor-associated molecular functions and pathways. In addition, we screened two ceRNA regulatory networks using Cox regression analysis and log-rank test. QRT-PCR assay identified the NAA11/hsa- miR-142-3p/GS1-39E22.2 regulatory axis of the ceRNA network to be associated with the malignant transformation of IDH-mutant astrocytoma.</p><p><strong>Conclusion: </strong>The discovery of this mechanism deepens our understanding of the molecular mechanisms of malignant transformation in astrocytomas and provides new perspectives for exploring glioma progression and targeted therapies.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting PD-1 in Squamous Cell Carcinoma: Flavonoid-based Therapeutics Unveiled through in silico and in vitro Approaches.","authors":"Neha Sharma, Rupa Mazumder, Pallavi Rai, Abhijit Debnath","doi":"10.2174/0115734099312638240830060525","DOIUrl":"https://doi.org/10.2174/0115734099312638240830060525","url":null,"abstract":"<p><strong>Introduction: </strong>Squamous cell carcinoma is a major public health concern, with traditional treatments such as surgery, chemotherapy, and radiation therapy frequently resulting in significant side effects. Immunotherapy targeting checkpoints such as PD-1, CTLA-4, and B7- H3 provides a more specific approach but incurs high costs due to monoclonal antibodies.</p><p><strong>Aim and objective: </strong>This study aims to investigate the potential of natural flavonoids as lowtoxicity, small molecule-based alternatives targeting the PD-1 immunological checkpoint for SCC treatment. It aims to identify and evaluate flavonoid compounds from the NPACT database for their efficacy through in silico and in vitro screenings.</p><p><strong>Method: </strong>Employing a comprehensive in silico approach, including SBVS, Drug Likeness, Toxicity Prediction, Consensus Molecular Docking, DFT, and 300 ns MD simulations, this study screened for flavonoids with high affinity to PD-1. Identified lead molecules were further validated through in-vitro assays, such as NRU, to assess their anticancer activities.</p><p><strong>Result: </strong>The flavonoid NPACT01407 showed high affinity for PD-1, favorable drug-like properties, low toxicity, and effective stability at the active site, along with an optimal IC50 value, highlighting its potential as an effective immunotherapeutic agent for SCC.</p><p><strong>Conclusion: </strong>The study highlights the potential of the flavonoid molecule NPACT01407 as a promising candidate for the immunotherapeutic treatment of Squamous cell carcinoma. These findings provide a solid basis for further experimental validation and drug development efforts, suggesting a novel, less toxic, and cost-effective approach to cancer treatment.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Potential Inhibitors of Three NDM Variants of <i>Klebsiella</i> Species from Natural Compounds: A Molecular Docking, Molecular Dynamics Simulation and MM-PBSA Study.","authors":"Nakul Neog, Minakshi Puzari, Pankaj Chetia","doi":"10.2174/0115734099294294240311061115","DOIUrl":"10.2174/0115734099294294240311061115","url":null,"abstract":"<p><strong>Background: </strong><i>Klebsiella</i> species have emerged as well-known opportunistic pathogens causing nosocomial infections with β-lactamase-mediated resistance as a prevalent antibiotic resistance mechanism. The discovery and emergence of metallo-β-lactamases, mainly new- Delhi metallo-β-lactamases (NDMs), have increased the threat and challenges in healthcare facilities.</p><p><strong>Objectives: </strong>A computational screening was conducted using 570 natural compounds from Dr. Duke's Phytochemical and Ethnobotanical data to discover promising inhibitors for NDM-6, NDM-9, and NDM-23 of the <i>Klebsiella</i> species.</p><p><strong>Methods: </strong>Using homology modeling on the Raptor-X web server, the structures of the three NDM variants were predicted. The structures were validated using various computational tools and MD simulation for 50 ns. Lipinski - Vebers' Filter and ADMET Screening were used to screen 570 compounds, followed by docking in Biovia Discovery Studio 2019 using the CDOCKER module. GROMACS was used to simulate the compounds with the highest scores with the proteins for 50 ns. Using the MM-PBSA method and g_<i>mmpbsa</i> tool, binding free energies were estimated and per-residue decomposition analysis was conducted.</p><p><strong>Results: </strong>The three structures predicted were found stable after the 50 ns MD Simulation run. The compounds Budmunchiamine-A and Rhamnocitrin were found to have the best binding energy towards NDM-6, NDM-9, and NDM-23, respectively. From the results of MD Simulation, MM-PBSA binding free energy calculations, and per-residue decomposition analysis, the Protein-ligand complex of NDM-6 with Budmunchiamine A and NDM-9 with Rhamnocitrin was relatively more stable than the complex of NDM-23 and Rhamnocitrin.</p><p><strong>Conclusion: </strong>The study suggests that Budmunchiamine-A and Rhamnocitrin are potential inhibitors of NDM-6 and NDM-9, respectively, and may pave a path for <i>in-vivo</i> and <i>in-vitro</i> studies in the future.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":"142-165"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D-QSAR, Pharmacophore Modeling, ADMET and DFT Studies of Halogenated Conjugated Dienones as Potent MAO-B Inhibitors.","authors":"Githa Elizabeth Mathew, Chonny Herrera-Acevedo, Marcus Tullius Scotti, Sunil Kumar, Avni Berisha, Savaş Kaya, Saleh Alfarraj, Mohammad Javed Ansari, Archana Dhyani, Sachithra Thazhathuveedu Sudevan, Mohan Kumar, Bijo Mathew","doi":"10.2174/0115734099307062240801053329","DOIUrl":"10.2174/0115734099307062240801053329","url":null,"abstract":"<p><strong>Introduction: </strong>It has been reported that the extension of conjugation in chalcone scaffolds considerably enhanced the potency, selectivity, reversibility, and competitive mode of MAO-B inhibition. In this study, using the experimental results of IC50 values of fifteen halogenated conjugated dienone derivatives (MK1-MK15) against MAO-B, we developed a 3DQSAR model.</p><p><strong>Methods: </strong>Further, we created a 3D pharmacophore model in active compounds in the series. The built model selected three variables (G2U, RDF115m, RDF155m) among the 653 AlvaDesc molecular descriptors, with a r² value of 0.87 and a Q² _cv for cross-validation equal to 0.82. The three variables were mostly associated with the direction of symmetry and the likelihood of discovering massive atoms at great distances. The evaluated molecules exhibited a good correlation between experimental and predicted data, indicating that the IC₅₀ value of the structure MK2 was related to the interatomic distances of 15.5 Å between bromine and chloro substituents. Furthermore, the molecules in the series with the highest activity were those with enhanced second component symmetry directional index from the 3D representation, which included the structures MK5 and MK6.</p><p><strong>Results: </strong>Additionally, a pharmacophore hypothesis was developed and validated using the decoy Schrodinger dataset, with an ROC score of 0.87 and an HHRR 1 fitness score that ranged from 2.783 to 3.00. The MK series exhibited a significant blood-brain barrier (BBB) permeability, according to exploratory analyses and <i>in silico</i> projections, and almost all analogues were expected to have strong BBB permeability.</p><p><strong>Conclusion: </strong>Further DFT research revealed that electrostatics were important in the interactions with MAO-B.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":"179-193"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Mechanisms of Sanguinarine in the Treatment of Osteoporosis by Integrating Network Pharmacology Analysis and Deep Learning Technology.","authors":"Yonghong Tang, Daoqing Zhou, Fengping Gan, Zhicheng Yao, Yuqing Zeng","doi":"10.2174/0115734099282231240214095025","DOIUrl":"10.2174/0115734099282231240214095025","url":null,"abstract":"<p><strong>Background: </strong>Sanguinarine (SAN) has been reported to have antioxidant, antiinflammatory, and antimicrobial activities with potential for the treatment of osteoporosis (OP).</p><p><strong>Objective: </strong>This work purposed to unravel the molecular mechanisms of SAN in the treatment of OP.</p><p><strong>Methods: </strong>OP-related genes and SAN-related targets were predicted from public databases. Differential expression analysis and VennDiagram were adopted to detect SAN-related targets against OP. Protein-protein interaction (PPI) network was served for core target identification. Molecular docking and DeepPurpose algorithm were further adopted to investigate the binding ability between core targets and SAN. Gene pathway scoring of these targets was calculated utilizing gene set variation analysis (GSVA). Finally, we explored the effect of SAN on the expressions of core targets in preosteoblastic MC3T3-E1 cells.</p><p><strong>Results: </strong>A total of 21 candidate targets of SAN against OP were acquired. Furthermore, six core targets were identified, among which CASP3, CTNNB1, and ERBB2 were remarkably differentially expressed in OP and healthy individuals. The binding energies of SAN with CASP3, CTNNB1, and ERBB2 were -6, -6.731, and -7.162 kcal/mol, respectively. Moreover, the GSVA scores of the Wnt/calcium signaling pathway were significantly lower in OP cases than in healthy individuals. In addition, the expression of CASP3 was positively associated with Wnt/calcium signaling pathway. CASP3 and ERBB2 were significantly lower expressed in SAN group than in DMSO group, whereas the expression of CTNNB1 was in contrast.</p><p><strong>Conclusion: </strong>CASP3, CTNNB1, and ERBB2 emerge as potential targets of SAN in OP prevention and treatment.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":"83-93"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Bioinformatics Analysis and Target Drug Prediction of Inflammatory Bowel Disease Co-existent Diabetes Mellitus.","authors":"Lili Yang, Ning Wang, Yutong Wang, Wen Li, Ziyang Kong, Bin Zhang, Yaoyao Bian","doi":"10.2174/0115734099282247231211111219","DOIUrl":"10.2174/0115734099282247231211111219","url":null,"abstract":"<p><strong>Introduction: </strong>Inflammatory bowel disease (IBD) has become one of the public problems worldwide and its incidence rate is increasing year by year. Its concomitant disease i.e. diabetes mellitus (DM) has attracted more and more attention due to DM altering the progression of IBD and leading to long periods of intermittent recurrence and deterioration. The common mechanism and potential target drug of IBD with comorbid chronic conditions of DM were explored.</p><p><strong>Methods: </strong>Gene expression profile data were downloaded from the Gene Expression Omnibus (GEO) public database. The differentially expressed genes (DEGs) were identified by R software. GO annotation and pathway enrichment were performed, a protein-protein interaction (PPI) network was constructed, associated lncRNAs were predicted and drug prediction targeting key genes was made. Additionally, the regulatory network among core genes, associated pathways, and predicted lncRNA in IBD with coexistent DM were visualized.</p><p><strong>Results: </strong>We identified the critical gene MMP3 with lncRNA CDKN2BAS involved in the PPAR pathway, which uncovered the underlying regulatory mechanism of IBD with coexistent DM. We also predicted the potential therapeutic compound ZINC05905909 acting on MMP3.</p><p><strong>Conclusion: </strong>Our findings revealed the regulatory mechanism chain of critical gene MMP3, lncRNA CDKN2BAS, and PPAR pathway and provided potential therapeutic compound ZINC05905909 for drug therapy to treat comorbid IBD DM.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":"129-141"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network Pharmacology, Molecular Docking and <i>in vivo</i>-based Analysis on the Effects of the MBZM-N-IBT for Arthritis.","authors":"Alok Kumar Moharana, Mahendra Gaur, Tapas Kumar Mohapatra, Rudra Narayan Dash, Bharat Bhusan Subudhi","doi":"10.2174/0115734099307360240731052835","DOIUrl":"10.2174/0115734099307360240731052835","url":null,"abstract":"<p><strong>Introduction: </strong>Arthritis is the cause of morbidity associated with Chikungunya virus (CHIKV) infection. It persists even after the virus has been cleared from the body. MBZM-NIBT was earlier shown to inhibit (CHIKV) infection <i>in vitro</i> and <i>in vivo</i>.</p><p><strong>Objectives: </strong>The objective of this study is to determine the ability of MBZM-N-IBT to manage arthritis independent of CHIKV infection.</p><p><strong>Methods: </strong>The acute toxicity of MBZM-N-IBT was determined to find a permissible oral dose. Effects against inflammation and arthritis were determined in relevant preclinical models. Network pharmacology was used to propose possible modes of action.</p><p><strong>Results: </strong>It showed no acute toxicity orally, with an estimated LD₅₀ of more than 5000 mg/kg in rats. It significantly reduced inflammation. Its effect against Complete Freund's Adjuvant (CFA) induced arthritis was comparable to that of Diclofenac sodium. Network pharmacology analysis revealed that MBZM-N-IBT can potentially interfere with multiple targets and pathways. MMP12 and CTSD were found to be the most probable hub targets of MBZM-N-IBT for its effect against arthritis.</p><p><strong>Conclusion: </strong>In conclusion, MBZM-N-IBT is safe at 50 mg/kg and can manage arthritis independent of CHIKV infection through modulation of multiple pathways and arthritis-associated targets.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":"194-210"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Synthesis, Biological and <i>in silico</i> Evaluation of Novel Indazole-pyridine Hybrids for the Treatment of Breast Cancer.","authors":"Ishan Panchal, Rati Kailash Prasad Tripathi, Mange Ram Yadav, Meet Valera, Kinjal Parmar","doi":"10.2174/0115734099308839240724100224","DOIUrl":"10.2174/0115734099308839240724100224","url":null,"abstract":"<p><strong>Introduction: </strong>The prevalence of breast cancer presents a substantial global health concern, underscoring the ongoing need for the development of inventive therapeutic remedies.</p><p><strong>Methods: </strong>In this investigation, an array of novel indazole-pyridine hybrids (5a-h) have been designed and synthesized to assess their potential as candidates for treating breast cancer. Subsequently, we have conducted biological evaluations to determine their cytotoxic effects on the human MCF-7 breast cancer cell line. Furthermore, <i>in silico</i> analysis was conducted to estimate the inhibition potential of the compounds against TrkA (Tropomyosin receptor kinase A), a specific molecular target associated with breast cancer, through molecular docking. In silico physicochemical and pharmacokinetic predictions were made to assess the compounds' drug-like properties.</p><p><strong>Results: </strong>Compound 5a emerged as the most active compound among the others with GI50 < 10 μg/ml. Besides, compound 5a showed high binding energy (BE -10.7 kcal/mol) against TrkA and was stabilized within the TrkA binding pocket through hydrophobic, H-bonding, and van der Waals interactions. <i>In silico</i> physicochemical and pharmacokinetic prediction studies indicated that compound 5a obeyed both Lipinski's and Veber's rule and displayed a versatile pharmacokinetic profile, implying compound 5a to appear as a viable candidate and that it could be further refined to develop therapeutic agents for potentially treating breast cancer.</p><p><strong>Conclusion: </strong>This study offers a promising direction for the advancement of innovative breast cancer treatments, highlighting the effectiveness of indazole-pyridine hybrids as potential anticancer agents. Further optimization and preclinical development are necessary to advance these compounds to clinical trials.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":"211-225"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Molecular Mechanism by which Kaempferol Attenuates Sepsis-related Acute Respiratory Distress Syndrome Based on Network Pharmacology and Experimental Verification.","authors":"Weichao Ding, Changbao Huang, Juan Chen, Wei Zhang, Mengmeng Wang, Xiaohang Ji, Shinan Nie, Zhaorui Sun","doi":"10.2174/0115734099295805240126043059","DOIUrl":"10.2174/0115734099295805240126043059","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Sepsis-related acute respiratory distress syndrome (ARDS) is a fatal disease without effective therapy. Kaempferol is a flavonoid compound extracted from natural plant products; it exerts numerous pharmacological effects. Kaempferol attenuates sepsis-related ARDS; however, the underlying protective mechanism has not been elucidated completely.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;This study aimed to use network pharmacology and experimental verification to investigate the mechanisms by which kaempferol attenuates sepsis-related ARDS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We screened the targets of kaempferol by PharMapper, Swiss Target Prediction, and CTD database. We identified the targets of sepsis-related ARDS by GeneCards, DisGeNet, OMIM, and TTD. The Weishengxin platform was used to map the targets of both kaempferol and sepsis-related ARDS. We created a Venn diagram to identify the intersection targets. We constructed the \"component-intersection targets-disease\" network diagram using Cytoscape 3.9.1 software. The intersection targets were imported into the STRING database for developing the protein-protein interaction network. Metascape was used for the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. We selected the leading 20 KEGG pathways to establish the KEGG relationship network. Finally, we performed experimental verification to confirm our prediction results.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Through database screening, we obtained 502, 360, and 78 kaempferol targets, disease targets of sepsis-related ARDS, and intersection targets, respectively. The core targets consisted of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, albumin (ALB), IL-1β, and AKT serine/ threonine kinase (AKT)1. GO enrichment analysis identified 426 items, which were principally involved in response to lipopolysaccharide, regulation of inflammatory response, inflammatory response, positive regulation of cell migration, positive regulation of cell adhesion, positive regulation of protein phosphorylation, response to hormone, regulation of reactive oxygen species (ROS) metabolic process, negative regulation of apoptotic signaling pathway, and response to decreased oxygen levels. KEGG enrichment analysis identified 151 pathways. After eliminating the disease and generalized pathways, we obtained the hypoxia-inducible factor 1 (HIF-1), nuclear factor κB (NF-κB), and phosphoinositide 3-kinase (PI3K)-Akt signaling pathways. Our experimental verification confirmed that kaempferol blocked the HIF-1, NFκκB, and PI3K-Akt signaling pathways, diminished TNF-α, IL-1β, and IL-6 expressions, suppressed ROS production, and inhibited apoptosis in lipopolysaccharide (LPS)-induced murine alveolar macrophage (MH-S) cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Kaempferol can reduce inflammatory response, ROS production, and cell apoptosis by acting on the HIF-1, NF-κB, and PI3K-Akt signaling pathways, thereby all","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":"166-178"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139699107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}