Current computer-aided drug design最新文献

{"title":"EGFR Kinase Inhibiting Amino-enones for Breast Cancer; CADD Approach.","authors":"Deena Gladies Raymond Mohanraj, Manikandan Alagumuthu, Subha Chellam, Abishek Suresh Kumar, Tejaswini Nagaraj Poojari, Jeevitha Suresh Kumar, Palaniraja Subramaniam","doi":"10.2174/0115734099266822231219073332","DOIUrl":"10.2174/0115734099266822231219073332","url":null,"abstract":"<p><strong>Background: </strong>The Computer-Aided Drug Discovery (CADD) approach was used to develop a few Epidermal Growth Factor Receptor (EGFR) kinase inhibitors. EGFR kinase expression is highly associated with genomic instability, higher proliferation, lower hormone receptor levels, and HER2 over-expression. It is more common in breast cancer. Thus, EGFR Kinase is one of the main targets in discovering new cancer medicine.</p><p><strong>Objectives: </strong>To computationally validate some amides substituted β-amino enones as EGFR inhibitors and to carry out associated <i>in vitro</i> anticancer agents.</p><p><strong>Methods: </strong>We used tools such as molecular docking, MD simulations, DFT calculations, and ADMET predictions <i>in silico</i> to establish a preliminary SAR. <i>in vitro</i>, we used BT474 (ER+HER2+) and MCF-7 (ER-HER2) cell lines along with normal breast cell epithelial cells (MFC-10a) for anticancer studies and EGFR kinase inhibition assay studies. As the Reactive Oxygen Species (ROS) plays the main role in cancer development, we also analyzed the antioxidant potentials of these compounds.</p><p><strong>Results: </strong>Among the family of eleven amides substituted (Z)-β-amino enones (5a-k), compounds 5b, 5c, 5g, and 5h showed valuable <i>in silico</i> and <i>in vitro</i> bio-activity. Remarkably, the <i>in-silico</i> results almost coincided with <i>in vitro</i> study results.</p><p><strong>Conclusion: </strong>We recommend compounds 5b, 5c, 5g, and 5h for pre-clinical and clinical evaluation to establish them as future cancer therapeutics.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":"549-558"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139652412","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 and <i>In Vivo</i> Experimental Verification of the Mechanism of the Qing'e Pill for Treating Intervertebral Disc Degeneration.","authors":"Hui Jin, Huaiyu Ma, Jie Wu, Ruizhe Wu, Haoran Xu, Weixing Chen, Linghui Li, Jingqi Zeng, Fan Wang","doi":"10.2174/0115734099356426241119051916","DOIUrl":"10.2174/0115734099356426241119051916","url":null,"abstract":"<p><strong>Objective: </strong>The Qing'e Pill (QEP) is widely used to alleviate low back pain and sciatica caused by Intervertebral Disc Degeneration (IDD). However, its active components, key targets, and molecular mechanisms are not fully understood. The aim of this study is to elucidate the molecular mechanisms through which the QEP improves IDD using database mining techniques.</p><p><strong>Methods: </strong>Active components and candidate targets of the QEP were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine. IDD-related targets were obtained from the GeneCards database, and liver- and kidney-specific genes were retrieved from the BioGPS database. The intersection of these candidate targets was analyzed to identify potential targets for the QEP in IDD. A protein-protein interaction network analysis was performed using STRING and Cytoscape 3.7.2 software. Core targets were further analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking was used to assess the binding affinity of active components to candidate targets, and animal experiments were conducted for validation.</p><p><strong>Results: </strong>We identified 65 potentially active components of the QEP that corresponded to 1,093 candidate targets, 2,108 IDD-related targets, and 1,113 liver- and kidney-specific genes. Key components included quercetin, berberine, isorhamnetin, and emodin. The primary candidate targets were Wnt5A, CTNNB1, IL-1β, MAPK14, MMP9, and MMP3. The GO and KEGG analyses revealed the involvement of these targets in Wnt signaling, TNF signaling, Wnt receptor activation, Frizzled binding, and Wnt-protein interactions. Molecular docking showed strong binding between these components and their targets. Animal experiments demonstrated that the QEP treatment significantly reduced the expression of Wnt5A, CTNNB1, IL-1β, MAPK14, MMP9, and MMP3 at high, medium, and low doses compared with the model group.</p><p><strong>Conclusion: </strong>The QEP alleviated IDD by modulating the Wnt/MAPK/MMP signaling pathways and reducing the release and activation of key factors.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":"534-548"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775850","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":"Xuebijing Exerts Protective Effects on Myocardial Cells by Upregulating TRIM16 and Inhibiting Oxidative Stress and Apoptosis.","authors":"Xiaoyan Meng, Xinming Yan, Peng Xue, Zhaoqing Xi","doi":"10.2174/0115734099318323241122184120","DOIUrl":"10.2174/0115734099318323241122184120","url":null,"abstract":"<p><strong>Objective: </strong>This study utilized transcriptomic sequencing combined with cellular and animal models to explore the potential mechanisms of Xuebijing in treating sepsis-induced myocardial dysfunction, also known as sepsis-induced myocardial injury.</p><p><strong>Methods: </strong>We investigated potential targets and regulatory mechanisms of XBJ injection using network pharmacology and RNA sequencing. The effects of XBJ on oxidative stress and apoptosis levels in human cardiac myocytes (AC16) and C57BL/6 mice exposed to lipopolysaccharide (LPS) were evaluated by Enzyme-Linked Immunosorbent Assay (ELISA), fluorescent probe, Fluorescent Quantitative Polymerase Chain Reaction (qPCR), Western Blot, Transmission Electron Microscopy, oxidative stress-related indicators detection kit, flow cytometry, and Immunohistochemistry (IHC).</p><p><strong>Results: </strong>First, it was verified that XBJ can reduce the deformation of AC16 cardiomyocytes induced by LPS and the production and secretion of ROS (P <0.01). The transcriptome sequencing results showed that the TRIM16 gene was significantly increased after XBJ treatment, and the data of KEGG and GO analyses demonstrated that XBJ could inhibit the pathway expression of oxidative stress damage in AC16 cells, and PCR verified that XBJ could indeed increase the expression level of TRIM16 gene in AC16 cells (P <0.01). Basic animal and cell experiments showed that LPS could inhibit the expression of TRIM16 and NRF2 in cardiomyocytes (P <0.05) and promote the expression of Keap1 (P <0.01), while XBJ could significantly upregulate the expression levels of TRIM16 and NRF2 (P <0.01) and inhibit the expression of Keap1 (P <0.01), thereby affecting the expression levels of downstream proinflammatory cytokines and alleviating LPS-induced oxidative stress damage. In addition, XBJ also inhibited the expression of the pro-apoptotic proteins Bax and c-caspase3 (P <0.01), promoted the expression of the anti-apoptotic protein Bcl2 (P <0.01), and reduced LPS-induced apoptosis by upregulating TRIM16.</p><p><strong>Conclusion: </strong>Our comprehensive data demonstrated that TRIM16 is a key gene in the therapeutic action of Xuebijing in sepsis-induced myocardial dysfunction, protecting myocardial cells from injury through antioxidative stress and anti-apoptotic mechanisms.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":"503-516"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775853","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":"Exploration of Pharmacological Mechanisms of Dapagliflozin against Type 2 Diabetes Mellitus through PI3K-Akt Signaling Pathway based on Network Pharmacology Analysis and Deep Learning Technology.","authors":"Jie Wu, Yufan Chen, Shuai Shi, Junru Liu, Fen Zhang, Xingxing Li, Xizhi Liu, Guoliang Hu, Yang Dong","doi":"10.2174/0115734099274407231207070451","DOIUrl":"10.2174/0115734099274407231207070451","url":null,"abstract":"<p><strong>Background: </strong>Dapagliflozin is commonly used to treat type 2 diabetes mellitus (T2DM). However, research into the specific anti-T2DM mechanisms of dapagliflozin remains scarce.</p><p><strong>Objective: </strong>This study aimed to explore the underlying mechanisms of dapagliflozin against T2DM.</p><p><strong>Methods: </strong>Dapagliflozin-associated targets were acquired from CTD, SwissTargetPrediction, and SuperPred. T2DM-associated targets were obtained from GeneCards and DigSee. VennDiagram was used to obtain the overlapping targets of dapagliflozin and T2DM. GO and KEGG analyses were performed using clusterProfiler. A PPI network was built by STRING database and Cytoscape, and the top 30 targets were screened using the degree, maximal clique centrality (MCC), and edge percolated component (EPC) algorithms of CytoHubba. The top 30 targets screened by the three algorithms were intersected with the core pathway-related targets to obtain the key targets. DeepPurpose was used to evaluate the binding affinity of dapagliflozin with the key targets.</p><p><strong>Results: </strong>In total, 155 overlapping targets of dapagliflozin and T2DM were obtained. GO and KEGG analyses revealed that the targets were primarily enriched in response to peptide, membrane microdomain, protein serine/threonine/tyrosine kinase activity, PI3K-Akt signaling pathway, MAPK signaling pathway, and AGE-RAGE signaling pathway in diabetic complications. AKT1, PIK3CA, NOS3, EGFR, MAPK1, MAPK3, HSP90AA1, MTOR, RELA, NFKB1, IKBKB, ITGB1, and TP53 were the key targets, mainly related to oxidative stress, endothelial function, and autophagy. Through the DeepPurpose algorithm, AKT1, HSP90AA1, RELA, ITGB1, and TP53 were identified as the top 5 anti-targets of dapagliflozin.</p><p><strong>Conclusion: </strong>Dapagliflozin might treat T2DM mainly by targeting AKT1, HSP90AA1, RELA, ITGB1, and TP53 through PI3K-Akt signaling.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":"452-465"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139418828","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":"Potential Mechanism by which Eriodictyol Protects against Doxorubicininduced Cardiotoxicity based on Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.","authors":"Chunmeng Qin, Mei Sun, Feng Lv, Dan Du, Wenjun Li, Songqing Liu","doi":"10.2174/0115734099297600240523105601","DOIUrl":"10.2174/0115734099297600240523105601","url":null,"abstract":"<p><strong>Background: </strong>The clinical use of doxorubicin (DOX), an anthracycline antibiotic with broad-spectrum applications against various malignant tumors, is limited by doxorubicininduced cardiotoxicity (DIC). Eriodictyol (ERD) has shown cardioprotective effects, but the mechanism of its protective effect on DIC remains unknown.</p><p><strong>Aims: </strong>This study aimed to explore the potential mechanisms by which ERD confers protection against DIC.</p><p><strong>Methods: </strong>ERD and DIC targets were identified from the TCMSP, PharmMaper, SwissTargetPrediction, TargetNet, BATMAN, GeneCards, and PharmGKB databases. Differential gene expression data between DIC and normal tissues were extracted from the GEO database. A protein‒ protein interaction (PPI) network of the intersecting ERD-DIC targets was constructed using the STRING platform and visualized with Cytoscape 3.10.0 software. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for ERD-DIC cross-targets were conducted. Validation included molecular docking with AutoDock Tools software and molecular dynamics simulations with Gromacs 2019.6 software.</p><p><strong>Results: </strong>Network pharmacology analysis revealed 43 intersecting ERD-DIC targets, including 6 key targets. GO functional enrichment analysis indicated that the intersecting targets were enriched in 550 biological processes, 45 cell components, and 41 molecular functions. KEGG pathway enrichment analysis identified 114 enriched signaling pathways. Molecular docking revealed a strong binding affinity between ERD and 6 key targets, as well as multiple targets within the ROS pathway. Molecular dynamics simulations indicated that ERD has favorable binding with 3 crucial targets.</p><p><strong>Conclusion: </strong>The systematic network pharmacology analysis suggests that ERD may mitigate DIC through multiple targets and pathways, with the ROS pathway potentially playing a crucial role. These findings provide a reference for foundational research and clinical applications of ERD in treating DIC.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":"316-332"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141285632","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":"Synthesis, Biological Evaluation, Molecular Docking Studies and ADMET Prediction of Oxindole-based Hybrids for the Treatment of Tuberculosis.","authors":"Vaishali Pavalbhai Patel, Rati Kailash Prasad Tripathi, Snigdha Das Mandal","doi":"10.2174/0115734099353857241022102426","DOIUrl":"10.2174/0115734099353857241022102426","url":null,"abstract":"<p><strong>Introduction: </strong>With a projected mortality toll of 1.4 million in 2019, tuberculosis (TB) continues to be a significant public health concern around the world. Studies of novel treatments are required due to decreased bioavailability, increased toxicity, increased side effects, and resistance of several first- and second-line TB therapies, including isoniazid and ethionamide.</p><p><strong>Methods: </strong>This study reports the synthesis of oxindole-based hybrids as potent InhA inhibitors targeting <i>Mycobacterium tuberculosis</i>. The synthesized compounds (5a-5e and 8a-8c) were evaluated for their anti-mycobacterial activity against <i>Mycobacterium tuberculosis</i> and nontuberculous mycobacteria (NTMs), viz. <i>M. abscessus</i> (ATCC 19977), <i>M. fortuitum</i> (ATCC 6841), and <i>M. chelonae</i> (ATCC 35752) using the Microplate Alamar Blue Assay (MABA). Molecular docking studies were performed using AutoDock Vina to explore the binding interactions of these compounds with the InhA enzyme (PDB: 2NSD). Additionally, biochemical and histopathological studies were conducted to assess the hepatotoxicity of the lead compounds. <i>Insilico</i> molecular properties and ADMET properties of the synthesized compounds were predicted using SwissADME and Deep-PK online tools to assess their drug-likeness.</p><p><strong>Results: </strong>Among the tested compounds, 8b exhibited significant anti-mycobacterial activity with a minimum inhibitory concentration (MIC = 1 μg/mL) comparable to the reference drug ethambutol. Further, the compound demonstrated a binding affinity and orientation similar to the reference inhibitor 4PI, indicating its potential as a potent InhA inhibitor, and was found to be stabilized within the binding pocket of InhA through H-bonding, hydrophobic and van der Waal's interactions. Besides, the compounds hepatotoxicity assessment studies depicted that 8b showed no significant liver dysfunction or damage to liver tissues. Additionally, 8b adhered to Lipinski's rule of five and Veber's rule, displaying favourable pharmacokinetic and drug-like properties, including high human intestinal absorption, distribution, and acceptable metabolic stability and excretion.</p><p><strong>Conclusion: </strong>Compound 8b emerged as a promising candidate for further optimization and development as a therapeutic agent for tuberculosis, offering a new avenue for tackling tuberculosis.</p>","PeriodicalId":93961,"journal":{"name":"Current computer-aided drug design","volume":" ","pages":"517-533"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559838","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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089709","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}