Current topics in medicinal chemistry最新文献

{"title":"Computational Drug Design of Natural Product-Based Azole Hybrids for Multifactorial Diseases: Success Stories.","authors":"Anupama Pandey, Anant Ram, Maitreyi Singh, Shipra Gautam, Shashi Pandey, R N Singh, Poonam Rawat","doi":"10.2174/0115680266414361260408102607","DOIUrl":"https://doi.org/10.2174/0115680266414361260408102607","url":null,"abstract":"<p><p>Complex diseases such as cancer, neurodegenerative disorders, and metabolic syndromes involve multiple interconnected biological pathways, often rendering single-target therapies ineffective. Conventional drugs frequently lead to undesirable side effects and contribute to Multidrug Resistance (MDR). Natural products, known for their structural diversity and relatively lower toxicity, have emerged as promising candidates for the development of multi-target therapeutic agents. Hybrid molecules, which combine pharmacophores from natural and synthetic origins, offer a novel strategy to simultaneously modulate multiple disease pathways. This review systematically compiles and analyzes studies on hybrid molecules derived from natural products with potential multi-target activity. Relevant literature was selected from scientific databases (PubMed, Scopus, Web of Science), and key hybrid scaffolds were examined with respect to design strategy, molecular docking performance, pharmacokinetic properties, and biological activity. Several classes of natural product-based hybrid molecules, such as triazoles, imidazoles, and tetrazoles, demonstrated effective binding to multiple disease-related targets. Computational studies revealed favorable binding energies and drug-like properties. Many of these hybrids showed potential to overcome MDR and improve therapeutic outcomes in preclinical studies. The reviewed hybrid molecules exhibit promising polypharmacological properties for treating multifactorial diseases. Their design often leverages the inherent bioactivity of natural products while enhancing selectivity and potency through synthetic modification. While encouraging, the findings remain primarily computational or in early-stage experimentation, and thus require further validation. Natural product-derived hybrid molecules represent a promising frontier in the development of multi-target therapies for complex diseases. Future research should focus on experimental validation, pharmacokinetic profile optimization, and in vivo efficacy studies. This approach may lead to the next generation of safer, more effective therapeutic agents.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simulated Natural Nanoparticles in Bai-Hu-Tang Decoction: Preparation, Characterization, Pharmacokinetics, and Antipyretic Effects.","authors":"Jianing Liu, Chunyu Liu, Yanwen Ling, Jin Su, Jiaming Lun, Yang Ping","doi":"10.2174/0115680266427221260406103333","DOIUrl":"https://doi.org/10.2174/0115680266427221260406103333","url":null,"abstract":"<p><strong>Introduction: </strong>Objective: The purpose of this study was to prepare a simulated form of N-BHT (Simu-N-BHT) using a counter-evidence method and to analyze the mechanism by which a natural nanophase was formed.</p><p><strong>Methods: </strong>The morphology of nanoparticles in each group was observed by transmission electron microscopy. The Simu-N-BHT nanoparticles were prepared by the decocting-dialysis method. The study also characterized Simu-N-BHT nanoparticles, in vitro release, in vivo pharmacokinetics, antipyretic effects, and pathological analysis.</p><p><strong>Results: </strong>Through the TEM images and correlation analysis of 15 groups, it can be seen that the formation of nano-colloidal particles is inseparable from japonica rice. The Simu-N-BHT nanoparticles were very similar to N-BHT nanoparticles in terms of morphology and were spherical, with a mean size of 223 ± 11.25 nm. Furthermore, Simu-N-BHT nanoparticles exhibited a crystal structure with specific thermodynamic properties. The pharmacokinetic behavior of these nanoparticles supports the non-compartmental model and exhibits antipyretic effects similar to those of N-BHT nanoparticles. The pathological results indicate that treatment with Simu-N-BHT can alleviate lung injury in rats.</p><p><strong>Discussion: </strong>The nano-phase solution obtained through modern pharmaceutical methods exhibits results similar to the naturally formed N-BHT in decoctions in terms of appearance, particle size, and thermodynamic properties. This provides new methods and experimental evidence for the research and development of novel traditional Chinese medicine preparations.</p><p><strong>Conclusion: </strong>This study ultimately provides a natural polymer carrier material-amylopectin derived from japonica rice-for the formation of spherical nanoparticles with smooth surface morphology.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dolabellane Diterpenes from the Marine Brown Alga Dictyota dolabellana and their Potential Antiviral Activity.","authors":"Joel Campos De-Paula, Ludmila Bomeny Bueno, Erick Alves Pereira Lopes-Filho, Milene Dias Miranda, Tamara Fogel, Thiago Moreno Lopes E Souza, Claudio Cesar Cirne-Santos, Rodrigo Bagueira de Vasconcellos Azeredo, Diana Negrão Cavalcanti, Izabel Christina Nunes de Palmer Paixão, Valéria Laneuville Teixeira","doi":"10.2174/0115680266428579260615172523","DOIUrl":"https://doi.org/10.2174/0115680266428579260615172523","url":null,"abstract":"<p><strong>Introduction: </strong>The brown alga Dictyota dolabellana is a rare species that was described based on morphological and natural product analyses from a population found in 2004 at Itaparica Island in Bahia, Brazil. However, it has not been found anywhere since then.</p><p><strong>Methods: </strong>The original crude acetonic extract was analyzed by 1H and 13C NMR and showed as the major secondary metabolite, the dolabellane diterpene (1S*, 2E, 4S*, 7S*, 8R*, 11S*, 12R*)-4- hydroxy-7,8-epoxy-2-dolabellene, which is the chemotaxonomic marker of this species. Two additional new diterpenes for this species were obtained: (1S*, 2E, 4S*,7R*, 8E, 11S*, 12R*)-4,7- hydroxy-2,8-dolabelladiene and (1R*, 4S*, 7R*, 8E, 11S*,12R*)-4,7-hydroxy-8-dolabellene. All three structures were assigned by 1D and 2D NMR spectral data.</p><p><strong>Results: </strong>Biological tests carried out with those three diterpenes revealed that diterpenes 1 and 2 inhibited the replication of herpes simplex virus type 1 (HSV-1) in a dose-dependent manner. Supplementary data showed that diterpene 1 has no inhibitory activity against the reverse transcriptase enzyme of human immunodeficiency virus type 1 (HIV-1 RT).</p><p><strong>Discussion: </strong>Finally, the antiviral and cytotoxic activities of dolabellanes of Dictyota spp depend on both the functionality of the molecule and the position of the hydroxyl groups and double bonds.</p><p><strong>Conclusion: </strong>This study may enhance the interest in D. dolabellana for its biotechnological applications, such as antiviral products and assist in its chemotaxonomy.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory Effects of Flavonoids from the Stems and Leaves of Scutellaria baicalensis Georgi on Oligodendrocyte Pyroptosis Induced by Aβ1-42.","authors":"Tangtang Song, Yazhen Shang","doi":"10.2174/0115680266471937260616073434","DOIUrl":"https://doi.org/10.2174/0115680266471937260616073434","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) is characterized not only by gray matter lesions but also by significant white matter damage and oligodendrocyte dysfunction. This study elucidates the pyroptosis-suppressive potential of Scutellaria baicalensis Georgi stem-leaf flavonoids (SSFs) in oligodendroglial lineage cells.</p><p><strong>Methods: </strong>We co-treated rat oligodendrocytes (OLN-93 cell line) with 7.5 μmol/L Aβ₁₋₄₂ to simultaneously induce pyroptosis and SSFs. We observed cell morphology via microscopy, measured cell viability with the MTT assay, and assessed membrane damage using the LDH release assay. We then used qPCR to measure the mRNA levels of myelin-related genes (MBP, MAG, MOG) and pyroptosis-related genes (NLRP3, Caspase-1, GSDMD). We employed Western blotting to quantify the expression of pyroptosis-related proteins.Immunofluorescence was. used to localize myelin proteins whereas pyroptosis indicators and applied PI/Hoechst staining was used to evaluate cell membrane permeability within cells.</p><p><strong>Results: </strong>SSFs at concentrations of 15-60 mg/L significantly improved cell morphology, increased cell survival, reduced LDH release, modulated the expression of relevant genes and proteins, decreased the proportion of cells with impaired membrane integrity, and reduced the fluorescence signal of the pyroptotic execution protein GSDMD. These effects were comparable to those of the commonly used positive control, 60 mg/L Ginkgo biloba extract (GBE).</p><p><strong>Discussion: </strong>This study found that SSFs can alleviate Aβ-induced oligodendrocyte pyroptosis by inhibiting the NLRP3 inflammasome pathway, thereby preserving myelin function. The limitations of this study include the exclusive use of cell line models, the unclear identity of the specific active ingredients in SSFs, and the lack of verification of their blood-brain barrier penetration. Further studies, including in vivo animal experiments, active component isolation, and pharmacokinetic research, are required to evaluate its therapeutic potential for AD fully.</p><p><strong>Conclusion: </strong>SSFs protect oligodendrocytes against Aβ-induced injury by inhibiting the NLRP3 inflammasome pathway.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical Study on the Luteolin-Self-Nanoemulsifying Drug Delivery System: Pharmacokinetics, Toxicity, and Antiulcer Activity Evaluation.","authors":"Rashmi Pathak, Phool Chandra","doi":"10.2174/0115680266406523251124080425","DOIUrl":"https://doi.org/10.2174/0115680266406523251124080425","url":null,"abstract":"<p><strong>Introduction: </strong>Utilising self-nanoemulsifying drug delivery systems (SNEDDS), several drugs have had their bioavailability increased. Despite having several pharmacological properties, luteolin's limited solubility limits both its bioavailability and its utilisation. Self-nanoemulsifying drug delivery systems (SNEDDS) were created to solve this issue. This study thus involved the formulation and evaluation of luteolin-loaded self-nanoemulsifying drug delivery systems in terms of pharmacokinetics, toxicity, and in vivo antiulcer activity.</p><p><strong>Methods: </strong>Luteolin-SNEDDS were formulated by conducting solubility testing of luteolin in various excipients, constructing a pseudo-ternary phase diagram, and characterizing the systems using emulsification time, percentage transmittance, thermodynamic stability, droplet size, polydispersity index, and morphological analysis (TEM). Additionally, the luteolin-SNEDDS formulations were evaluated for acute oral toxicity, pharmacokinetic parameters, in vivo antiulcer efficacy, and antioxidant activity in stomach tissue.</p><p><strong>Results: </strong>The luteolin-SNEDDS was prepared using Tween 80, propylene glycol, and olive oil as surfactant, co-surfactant, and oil phase, respectively. The emulsification ability and droplet size were then optimised. The resulting luteolin-SNEDDS formulations had an emulsification time of 10 seconds and a droplet size of less than 100 nm. The pharmacokinetic investigation demonstrated enhanced systemic drug absorption, raising oral bioavailability, and additional assessments revealed these luteolin-SNEDDS as safe. On stomach tissue, luteolin-SNEDDS demonstrated strong anti-ulcer and in vivo antioxidant properties.</p><p><strong>Discussion: </strong>The luteolin-loaded SNEDDS significantly improved luteolin's solubility and oral bioavailability, as evidenced by rapid emulsification and nanoscale droplet formation. Pharmacokinetic results confirmed higher systemic exposure compared to pure luteolin. The formulation exhibited notable anti-ulcer and antioxidant effects in vivo, demonstrating therapeutic potential. Overall, luteolin-SNEDDS appeared to be a safe and effective strategy to enhance luteolin's pharmacological applications.</p><p><strong>Conclusion: </strong>Luteolin's gastroprotective properties and antioxidant efficacy can be improved by SNEDDS, according to research, and it has a good probability of becoming a bioactive substance used as an anti-ulcer agent.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of Huangqishihu Decoction in Treating Liver Fibrosis in Rats Model via Regulation of Oxidative Stress and Nrf2 Signaling Pathway.","authors":"Ling Feng, Ting Tang, Zhidan Wei, Yiying Yang, Zhaoxia Huang, Yongqin Zhang","doi":"10.2174/0115680266378645251027113519","DOIUrl":"https://doi.org/10.2174/0115680266378645251027113519","url":null,"abstract":"<p><strong>Introduction: </strong>Liver fibrosis (LF), a pathological wound-healing response to chronic injury, lacks effective pharmacological treatments. While Huangqishihu Decoction (HQSHD) shows clinical efficacy against LF, its molecular mechanisms remain unclear. This study investigated HQSHD's anti-fibrotic mechanisms through integrated network pharmacology and experimental validation.</p><p><strong>Methods: </strong>Active compounds and targets were identified using TCMSP, Batman-TCM, and GeneCards databases. Protein-protein interaction networks were constructed using STRING, and pathway analysis was performed in Metascape. Molecular docking validated compound-target interactions. In vivo validation was performed in CCl4-induced fibrotic rats, assessing serum biochemistry, histopathology, and molecular markers (qRT-PCR/Western blot).</p><p><strong>Results: </strong>We identified 64 bioactive compounds in HQSHD and 154 LF-related targets. Core targets (AKT1, CASP3, BCL2, STAT3) modulated multiple pathways including Nrf2 signaling. Molecular docking confirmed strong binding (energy < -7.0 kcal/mol) between the key compounds (quercetin and luteolin) and their targets. In vivo, HQSHD significantly reduced ALT (p<0.01), hydroxyproline (p<0.01), α-SMA (p<0.05), and collagen I (p<0.05) while upregulating Nrf2/HO-1 (p<0.05). It restored apoptosis balance (CASP3↑/BCL2↓, p<0.05).</p><p><strong>Discussion: </strong>HQSHD exerts anti-fibrotic effects through: 1) ECM (extracellular matrix) reduction via α-SMA/collagen I suppression, 2) Nrf2-mediated antioxidant activation, and 3) apoptosis regulation. This multi-target action addresses key LF drivers, including oxidative stress and inflammation.</p><p><strong>Conclusion: </strong>HQSHD combats LF via coordinated modulation of ECM deposition, oxidative stress, and apoptosis. Our findings provide mechanistic validation for its clinical use and highlight its potential as a multi-target anti-fibrotic therapy.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurodegenerative Disease Molecular Therapeutics based on Structural Activity Connections of Microglia Activation and Priming: A Comprehensive Review.","authors":"M D Abubakar, Janmejay Gupta, Rajni Daksh, Pavan Ramrao Chavan, Shahnaz Alom, Abhishek Mondal, Sk Azizuddin, Biplab Pal, Krishna Murti, Dileep Kumar, Nitesh Kumar","doi":"10.2174/0115680266405995260414053514","DOIUrl":"https://doi.org/10.2174/0115680266405995260414053514","url":null,"abstract":"<p><strong>Introduction: </strong>In neurodegenerative diseases (NDDs) such as Alzheimer's (AD) and Parkinson's (PD), neuroinflammation plays a crucial role in the development and advancement of these disorders by contributing to the buildup of defective protein folding. Native immune response cells, known as microglial cells, enhance neuroinflammation by altering their shape and producing cytokines that promote inflammation. Inflammation in NDDs causes synapse pathology and dysfunction, although microglia-synapse relationships are unclear. Microglial structural activity alters physiology and architecture, causing functional changes and degeneration. Neurodegeneration and protein accumulation trigger microglial priming, which activates and regenerates microglia, resulting in heightened inflammatory responses. The biological activities and structural activation of microglia are studied to improve NDD therapy.</p><p><strong>Methods: </strong>An exhaustive search was conducted using the internet databases of PubMed, ScienceDirect, Google Scholar, DOAJ, and Wiley to identify any papers that discussed microglial activation, priming of this process, and molecular intervention in NDDs. First, molecular, preclinical, and clinical data were carefully reviewed for extraneous or redundant references, then narratively merged to offer a conceptual overlay.</p><p><strong>Results: </strong>This review examines the role of microglial cells in NDDs, highlighting potential interventions such as peptide- and RNA-based therapies, NF-κB, TLR4, JAK inhibitors, antibodies, and biologics.</p><p><strong>Discussion: </strong>The results suggest that stimulating microglial cells and enhancing neuron connections may improve treatment outcomes. The review indicates that translational research should be conducted to connect molecular pathways with clinically effective medicines.</p><p><strong>Conclusion: </strong>Targeting microglia- and astrocyte-driven molecular markers could help resolve neuroinflammation and facilitate reliable therapeutic interventions in the progression of NDDs.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microtubule Stabilization as a Therapeutic Strategy: Updated Perspectives on Alzheimer's Disease and Neurodegenerative Tauopathies.","authors":"Darius J Yohannan, Kurt R Brunden, Thibault Alle","doi":"10.2174/0115680266465362260603045901","DOIUrl":"https://doi.org/10.2174/0115680266465362260603045901","url":null,"abstract":"","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BMS-CTMC-2025-461Ubiquitin as a Putative Causal Immune Orchestrator in Initial COVID-19 Severity: A Mendelian Randomization and Multi-Omics Study.","authors":"Yueyue Wang, Sirui Cai, Yubo Sun, Junqi Zhang, Jiaqi Ding, Jing Wang, Xiyang Zhang, Yuanhang Chang, Zhenchi Fang, Anqi Yue, Kun Yang, Dongbo Jiang","doi":"10.2174/0115680266458416260529222552","DOIUrl":"https://doi.org/10.2174/0115680266458416260529222552","url":null,"abstract":"<p><strong>Introduction: </strong>The initial COVID-19 outbreak precipitated unprecedented health crises, with research impeded by containment protocols and the high mortality rate. While SARS-CoV-2 perturbs immune ubiquitin dynamics, the causal interplay between them remains uncharacterized.</p><p><strong>Methods: </strong>We integrated multi-omics and Mendelian randomization (MR) approaches, including bidirectional and two-step MR, to assess causality between ubiquitination and initial COVID-19 severity and to determine whether immune cells mediate this relationship. Transcriptomic profiling, protein-protein interaction networks, immune-correlation analysis, and an elastic-net-derived prognostic model were employed to explore these interactions further and identify potential biomarkers.</p><p><strong>Results: </strong>Bidirectional MR confirmed causal links between COVID-19 severity and ubiquitination, identifying 13 ubiquitin-related genes with altered expression. A two-step MR analysis of 731 immune cell traits revealed CD45RA+ CD8+ T cells as a mediator of severe COVID-19-induced ubiquitin dysregulation (mediation proportion: 5.797%). A prognostic model based on ISG15, UBE2B, and UBE2V1 demonstrated high predictive accuracy in the training cohort (AUC up to 0.977) and maintained good predictive power in the testing cohort (AUC: 0.672-0.819), with significant risk stratification (log-rank P < 0.001).</p><p><strong>Discussion: </strong>We propose that ubiquitin may function as a causal immune orchestrator, shaping clinical outcomes in the initial phase of COVID-19. The derived ubiquitin gene prognostic model demonstrates potential for clinical risk stratification, while pathway enrichment and druginteraction analyses suggest opportunities for repurposing ubiquitin-related targets in COVID-19 therapy.</p><p><strong>Conclusion: </strong>This ubiquitin-centric framework advances precision management of severe COVID- 19, highlights the potential of ubiquitin-related targets for drug development, and establishes a multi-omics MR-based paradigm for future viral pandemics.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148257681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental Pollutant Tetrachloro-1,4-benzoquinone Exerts Neurotoxicity and Potential Protective Effects of Curcumin: A Network and Mendelian Randomization Analysis.","authors":"Chunshu Rong, Zhen Wei, Donge Xie, Qingyuan Wang, Haoxu Ren, Xu Wang, Dexi Zhao","doi":"10.2174/0115680266461615260518205032","DOIUrl":"https://doi.org/10.2174/0115680266461615260518205032","url":null,"abstract":"<p><strong>Introduction: </strong>The neurotoxicity mechanisms of tetrachloro-1,4-benzoquinone(TCBQ) remain poorly understood. This study integrated computational simulations validation to elucidate TCBQ-induced neurotoxicity.</p><p><strong>Methods: </strong>In our investigation of the neurotoxic effects of TCBQ, we employed a diverse range of analytical techniques, including protein-protein interaction (PPI) networks, screening for target genes and protective drugs, as well as performing KEGG (Kyoto Encyclopedia of Genes and Genomes) and GO (Gene Ontology) analyses. Additionally, we utilized advanced methodologies such as molecular docking and molecular dynamics simulations to gain deeper insights into the mechanisms underlying TCBQ's neurotoxicity. These comprehensive approaches enabled us to construct a detailed understanding of how TCBQ may contribute to neurotoxic outcomes. To further assess the potential connections between key target proteins and Alzheimer's disease, we utilized Mendelian randomization as a robust analytical strategy. This statistical method allowed us to explore the causal relationships that may exist between the identified proteins and the incidence of Alzheimer's disease, providing a clearer understanding of the biological pathways involved. For our analysis, we extracted summary-level data regarding the circulating levels of 4,907 proteins from a significant protein quantitative trait loci study conducted by the deCODE Genetics Consortium, which comprised a total of 35,559 individuals. Moreover, the outcome data for Alzheimer's disease were obtained from genome-wide association studies organized by the International Genomics of Alzheimer's Project (IGAP). This extensive research analyzed data from 17,008 participants who were diagnosed with Alzheimer's disease, alongside 37,154 control subjects, all of whom shared a European ancestry.</p><p><strong>Results: </strong>The results of integrated network analysis indicate that TCBQ may promote neurotoxicity through alzheimer 's disease. The main targets involved TNF, NOS2, IL6, and others. TCBQ and protective drug curcumin have a low binding score and compact complex with TNF, NOS2, IL6. 5 TNF subtype TNFSF13B, TNFRSF1B, TNFRSF13C, TNFSF12, NFRSF11B has a causal relationship with Alzheimer's disease.</p><p><strong>Discussion: </strong>TCBQ can promote neurotoxicity by increasing inflammation and alzheimer 's disease.</p><p><strong>Conclusion: </strong>Our study provides a theoretical basis for the subsequent experimental study of TCBQ in neurotoxicity. TNF plays an important role in alzheimer 's disease.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148223937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}