European Journal of Medicinal Chemistry Reports最新文献

{"title":"In silico and In vitro profiling of lariciresinol against PLA2: A molecular approach to regulate inflammation","authors":"Fathimath Henna ,&nbsp;G. Arun Kumar ,&nbsp;Amritha Thaikkad ,&nbsp;T.K. Varun ,&nbsp;E. Jayadevi Variyar ,&nbsp;Rajesh Raju ,&nbsp;J. Abhithaj","doi":"10.1016/j.ejmcr.2025.100290","DOIUrl":"10.1016/j.ejmcr.2025.100290","url":null,"abstract":"<div><div>Chronic inflammation underlies various diseases, including cardiovascular disorders, cancer, and autoimmune conditions. Phospholipase A2 (PLA2) plays a central role in the inflammatory response by hydrolyzing membrane phospholipids to release arachidonic acid, a precursor for pro-inflammatory eicosanoids via the COX and LOX pathways. Due to its upstream regulatory function, PLA2 presents a strategic target for inflammation control. However, developing safe and effective PLA2 inhibitors remains challenging due to limitations in efficacy and side effects.</div><div>Natural compounds, particularly phytochemicals with anti-inflammatory potential, are gaining attention as alternative therapeutics. This study investigated Lariciresinol, a phenolic lignan from Zingiber officinale (ginger), for its inhibitory activity against PLA2. Selected through <em>in silico</em> screening, Lariciresinol was evaluated using molecular docking, molecular dynamics (MD) simulations, and <em>in vitro</em> enzyme inhibition assays. The compound showed competitive inhibition with an IC50 of 57.6μM. The binding energy of Lariciresinol improved from −24.71kcal/mol to −34.38kcal/mol after MD simulations. The results from the binding energy analysis and MD simulations revealed stable interactions with key catalytic residues, supporting its proposed mechanism of action.</div><div>Further <em>in silico</em> analysis of Root Mean Square Deviation, Root Mean Square Fluctuation, Radius of Gyration, H-bonds, Solvent Accessible Surface Area, and Free Energy Landscape validated the results. These results highlight Lariciresinol a promising scaffold for developing novel PLA2-targeted anti-inflammatory agents, warranting further <em>in vitro</em> and <em>in vivo</em> validation for clinical application.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100290"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144750757","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":"Targeted regulatory strategies for VCAM-1 in multisystem diseases","authors":"Ruirong Peng ,&nbsp;Yu Zhang ,&nbsp;Zhenyu He ,&nbsp;Yueling Pang ,&nbsp;Huanhuan Ma ,&nbsp;Ming Fang ,&nbsp;Xiaoshan Ding ,&nbsp;Yanan Wang ,&nbsp;Zhihong Du ,&nbsp;Fanming Kong ,&nbsp;Liping Chen ,&nbsp;Yongqi Liu ,&nbsp;Ling Li ,&nbsp;Jiawei Li","doi":"10.1016/j.ejmcr.2025.100300","DOIUrl":"10.1016/j.ejmcr.2025.100300","url":null,"abstract":"<div><div>Systemic diseases are conditions caused by multiple factors (such as immune disorders, inflammation, tumors, etc.) that affect multiple organs, tissues, or systems throughout the body. These diseases are typically characterized by complex pathological states and diverse clinical symptoms. Vascular cell adhesion molecule-1 (VCAM-1) is a multifunctional transmembrane protein that plays a key role in various pathological processes, including inflammation, immune responses, and tumor progression, by mediating immune cell adhesion, regulating the tumor microenvironment, and facilitating signal transduction. This article aims to review the mechanistic roles of VCAM-1 in systemic diseases affecting the circulatory, respiratory, and digestive systems, as well as the association between VCAM-1 and tumor characteristics. Additionally, it discusses targeted therapeutic drugs (including traditional Chinese medicine and Western medicine) that regulate VCAM-1 for disease treatment, providing a theoretical basis for clinical research.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100300"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216489","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":"Anti-scarring drug discovery: potential targets and therapeutic opportunities","authors":"Meiling Feng ,&nbsp;Xiaotian Niu ,&nbsp;Shan Wang ,&nbsp;Liuxin Lu ,&nbsp;Xilong Feng ,&nbsp;Xiaoying Jiang ,&nbsp;Wenchao Chen ,&nbsp;Renren Bai","doi":"10.1016/j.ejmcr.2025.100283","DOIUrl":"10.1016/j.ejmcr.2025.100283","url":null,"abstract":"<div><div>Scar formation is a ubiquitous pathological response during the skin wound healing process. While physical therapy can effectively mitigate scar development, it is often accompanied by issues such as poor patient compliance and a range of side effects. Consequently, there is an urgent clinical need for the discovery of effective anti-scarring drugs. However, this need has not been fully addressed to date. This review delves systematically and comprehensively into the characteristics of scars, the underlying mechanisms of their formation, and potential therapeutic targets. Additionally, it reviews drug repurposing efforts, natural products and small molecule compounds in the drug discovery stage with anti-scarring effects. The information presented herein will offer valuable insights and enlightenment for exploring potential targets and pathways, as well as viable lead compounds for the discovery and development of novel anti-scarring drugs.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100283"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490946","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":"Novel triazole-based coumarin compounds as acetylcholinesterase inhibitors: Evidence and mechanism of 3-acetyl coumarin tethered (2-bromophenyl)-1,2,3 triazole as a potential mixed type inhibitor","authors":"Naseer Ahmad Dar ,&nbsp;Owais Hassan Wani ,&nbsp;Yuanyuan Wang ,&nbsp;Faez Iqbal Khan ,&nbsp;Bilal A. Ganie ,&nbsp;Syed Wajaht A. Shah ,&nbsp;Tanveer Ali Dar ,&nbsp;Tabasum Ismail","doi":"10.1016/j.ejmcr.2025.100289","DOIUrl":"10.1016/j.ejmcr.2025.100289","url":null,"abstract":"<div><div>Acetylcholinesterase (AChE) inhibition remains an important therapeutic strategy for Alzheimer's diseases, prompting immense research for novel and efficient small-molecule inhibitors. In this context, the present study describes the synthesis, characterization and evaluation of novel ether-linked 3-acetyl triazole-substituted coumarin derivatives as potential AChE inhibitors. The synthetic route involved 3-acetyl-7-hydroxycoumarin preparation through the reaction of 2,4-dihydoxybenzaldehyde with ethyl acetoacetate. Following alkylation at hydroxyl group, the acetylated 7-hydroxycoumarin underwent 1,3-dipolar cycloaddition i.e., Huisgen cycloaddition with various aromatic azides under sharpless click chemistry conditions, leading to the formation of a library of 16 novel coumarin tethered 1,2,3-triazole derivatives. Following synthesis and characterization using ¹H NMR, ¹³C NMR and IR spectroscopy, the AChE inhibitory potential of the coumarin derivatives was assessed, yielding IC₅₀ value in the range of 2.18 μM–67.89 μM. Among them, compound <strong>9</strong> exhibited the most potent inhibition (IC₅₀ = 2.18 μM), although lower than that of the standard inhibitor, eserine. Kinetic analysis indicated that compound <strong>9</strong> acted as a mixed-type inhibitor, with a K_i of 8.13 ± 0.18 μM. <em>In silico</em> simulation analysis elucidated the critical interactions between compound <strong>9</strong> and key AChE residues, including hydrogen bonding with Tyr121 and His444 and π-π stacking with Tyr334 and Trp283, supporting its strong binding affinity for the enzyme. Furthermore, the binding free energy calculations also confirmed the favourable thermodynamic interactions between the compound <strong>9</strong> and AChE. Collectively, the present findings highlight the therapeutic potential of compound <strong>9</strong> and establish this novel coumarin-triazole scaffold as a promising lead candidate for further optimization in development of AChE-targeted Alzheimer's therapeutics.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100289"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144750758","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":"Discovery of highly potent α-keto ester-based peptidomimetic inhibitors of the Hip1 protease for the treatment of Mycobacterium tuberculosis","authors":"Nicholas Schumann ,&nbsp;Farah Shamma ,&nbsp;Cory L. Brooks ,&nbsp;Sean J. Johnson ,&nbsp;Matthew K. Yim ,&nbsp;Keith J. Olsen ,&nbsp;Karla Peña ,&nbsp;Petros C. Karakousis ,&nbsp;Andrew Abell ,&nbsp;Nathan E. Goldfarb","doi":"10.1016/j.ejmcr.2025.100311","DOIUrl":"10.1016/j.ejmcr.2025.100311","url":null,"abstract":"<div><div><em>Mycobacterium tuberculosis</em> (Mtb), the bacterium responsible for tuberculosis, is the leading cause of death due to a single infectious agent. Given the alarming increase in drug-resistant cases, therapeutic agents targeting novel Mtb drug targets are urgently needed. Hip1, a serine protease required for Mtb survival in macrophages and tolerance to various antibiotics, has been identified as an attractive therapeutic target. In the current study, we describe the design and synthesis of highly potent (pM range <em>K</em>_i<em>)</em> peptidomimetic α-keto ester inhibitors of Hip1. We also report the first two X-ray cocrystal structures of Hip1 bound to these compounds and describe the binding interactions in the active site of recombinant Hip1. Finally, we show that these compounds effectively reduce the intracellular bacillary burden in a macrophage model of Mtb infection.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100311"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516720","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":"Screening of G-quadruplex DNA ligands by fluorescence detection of peptide displacement","authors":"Valentina Arciuolo ,&nbsp;Simona Marzano ,&nbsp;Rossella Buono,&nbsp;Nicola Grasso,&nbsp;Anna Di Porzio,&nbsp;Antonio Randazzo,&nbsp;Bruno Pagano,&nbsp;Jussara Amato","doi":"10.1016/j.ejmcr.2025.100293","DOIUrl":"10.1016/j.ejmcr.2025.100293","url":null,"abstract":"<div><div>G-quadruplexes (G4s) are noncanonical DNA/RNA structures involved in key cellular processes, and their interactions with proteins are emerging as therapeutic targets. However, strategies to identify ligands that bind G4s and potentially modulate these interactions remain limited. Here, we describe a fluorescence-based assay for rapid, quantitative evaluation of small molecules that bind G4s and potentially interfere with protein recognition. The method employs a fluorophore-labeled peptide derived from a conserved G4-binding protein motif, and a G4-forming sequence labeled with a fluorescence acceptor. Ligand-induced peptide displacement is detected via fluorescence increase. A panel of known G4 ligands was tested, and results correlated with binding affinities. A duplex DNA competition assay further assessed ligand selectivity. This method provides a scalable tool for screening G4 ligands with ability to compete with G4-recognition motifs, supporting drug discovery efforts.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100293"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144826996","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":"Naphthalimide-polyamine conjugates: a promising avenue for targeted anticancer therapy","authors":"Zhiyong Tian ,&nbsp;Luyao Tian ,&nbsp;Chaojie Wang","doi":"10.1016/j.ejmcr.2025.100285","DOIUrl":"10.1016/j.ejmcr.2025.100285","url":null,"abstract":"<div><div>Although chemotherapy is fundamental in cancer therapy, its effectiveness is restricted by systemic toxicity and drug resistance. By combining DNA intercalation, topoisomerase inhibition, and tumor microenvironment modulation, naphthalimide-polyamine conjugates have emerged as promising agents targeting multiple pathways. This review explores how structural innovations in conjugates can overcome therapeutic resistance and minimize off-target effects. In the past, early derivatives such as amonafide encountered clinical challenges because of dose-limiting myelosuppression (e.g., &gt;400 mg/m²). Nonetheless, recent progress in polyamine-mediated targeting and nanocarrier delivery has rejuvenated this class. We present a new Type I-VII classification approach that relates structural modifications—like heterocyclic fusion, polyamine chain adjustments, and substituent effects—to mechanistic outcomes. For example, compounds such as BND-12 inhibit metastasis in hepatocellular carcinoma by 61.8 % through ROS-induced mitochondrial dysfunction, whereas LU-79553 shows sub-micromolar effectiveness (IC₅₀ ≤ 0.32 μM) in colorectal cancer with minimal hematotoxicity. <strong>Key advancements include</strong>: (1) <strong>Triple-action synergy,</strong> which simultaneously induces DNA damage through p53/PARP-1, disrupts autophagy regulation, and inhibits VEGF/MMP, thereby interfering with adaptive resistance mechanisms. (2) <strong>Targeted delivery</strong>: The use of polyamine transporters (PAT) and nanocarriers boosts tumor selectivity, as shown by compound <strong>17</strong>, which reduces cisplatin resistance by 2–9 times by depleting lysosomal polyamines. (3) <strong>Structure-activity relationship (SAR) design:</strong> Adding a chlorine atom at the C₄ position, such as in 4-ClNAHSPD, enhances DNA binding affinity (Kb = 1.7 × 10⁴ M⁻¹) and increases γ-H₂AX foci formation by 1.8 times, while rigid cycloalkanediamine linkers improve cell cycle arrest. Preclinical success has been achieved, yet problems with metabolic stability and neurotoxicity persist. Future research focuses on AI-driven polyamine enhancement, nanoplatforms that can cross the blood-brain barrier (such as Angiopep-2-functionalized Ti@FeAu), and non-apoptotic cell death mechanisms like pyroptosis. Through the integration of structural innovation and multi-mechanistic synergy, this research sets up a design framework for precision oncology, illustrated by AI-optimized polyamine chains and nanoplatforms capable of crossing the blood-brain barrier. These methods provide a practical strategy for future cancer therapies aimed at overcoming adaptive resistance.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100285"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144826997","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":"Triazenes as inhibitors of HIV-1 and HCoV-OC43: A structure-activity relationship study","authors":"Natacha Mérindol ,&nbsp;Seyedeh Mahsa Hashemian ,&nbsp;Seynabou Sokhna ,&nbsp;Marie-Pierre Girard ,&nbsp;Marc Presset ,&nbsp;Insa Seck ,&nbsp;Lalla Aïcha Ba ,&nbsp;Seydou Ka ,&nbsp;Samba Fama Ndoye ,&nbsp;Issa Samb ,&nbsp;Erwan Le Gall ,&nbsp;Lionel Berthoux ,&nbsp;Matar Seck ,&nbsp;Isabel Desgagné-Penix","doi":"10.1016/j.ejmcr.2025.100288","DOIUrl":"10.1016/j.ejmcr.2025.100288","url":null,"abstract":"<div><div>Triazenes, or amino-substituted diazenes, are organic compounds containing three contiguous nitrogen atoms, that have potent biological activities. We previously demonstrated that triazenes, particularly those substituted with a phenyl or 3-pyridyl ring at the 1-position and a 2-pyridyl ring at the 3-position, exhibit anti-DENV properties. Here, we evaluated the antiviral activity against a betacoronavirus (HCoV-OC43) and a lentivirus (HIV-1). 1-(4-trifluoromethylphenyl)-2-imidazole-1-yldiazene (<strong>21</strong>) exhibited broad-spectrum activity (EC₅₀ = 6.6–6.8 μM) but was cytotoxic to THP-1 cells. Pyridyl triazenes (<strong>14, 15</strong>) were the most potent against HCoV-OC43, while 1-(4-methoxyphenyl)-2-morpholin-4-yldiazene (<strong>6</strong>) and 1-(4-methoxyphenyl)3-(-6-methylpyridin-2-yl)triazene (<strong>10</strong>) inhibited HIV-1 the most. Structure–activity relationship analysis, supported by molecular docking, indicated that <em>para</em>-methoxy groups favored interactions with viral enzyme binding pockets, enhancing antiviral potency, while <em>meta</em> and <em>para</em>-trifluoromethyl groups were associated with reduced activity and increased cytotoxicity. These findings support the further development of triazenes as antiviral scaffolds.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100288"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144686407","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":"Cheminformatics in advancing dengue antiviral research: From conventional molecular modeling (MM) to current artificial intelligence (AI) approaches","authors":"Rinki Prasad Bhagat ,&nbsp;Sk Abdul Amin ,&nbsp;Lucia Sessa ,&nbsp;Simona Concilio ,&nbsp;Stefano Piotto ,&nbsp;Shovanlal Gayen","doi":"10.1016/j.ejmcr.2025.100295","DOIUrl":"10.1016/j.ejmcr.2025.100295","url":null,"abstract":"<div><div>Cheminformatics has rapidly evolved and garnered widespread attention due to its potential to accelerate the process and reduce the cost of drug design and development. These technologies play a crucial role in drug design against dengue virus (DENV), a neglected tropical disease that remains a significant global health burden, with millions of cases reported annually. Recent advancements in cheminformatics and artificial intelligence (AI)-driven approaches offer promising strategies for designing inhibitors targeting key viral proteins. This study explores the applications of various cheminformatics methods, including conventional molecular modeling (pharmacophore mapping, molecular docking, molecular dynamics (MD) simulations, virtual screening), and artificial intelligence (AI)/machine learning (ML)-based strategies reported to identify compounds with high affinity and specificity for critical DENV protein targets. Additionally, it highlights the synergy between experimental validation, and <em>in silico</em> predictions to prioritize candidate molecules for further development.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100295"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895363","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":"Flavonoid-mediated modulation of Tau protein: Implications for targeted therapeutics and clinical relevance in Tau-related disorders","authors":"Rayane Hedna ,&nbsp;Emmanuelle T. Relave ,&nbsp;Maxime Robin ,&nbsp;Hervé Kovacic ,&nbsp;Gilles Breuzard","doi":"10.1016/j.ejmcr.2025.100309","DOIUrl":"10.1016/j.ejmcr.2025.100309","url":null,"abstract":"<div><div>Tau protein displays a key role in promoting tubulin assembly and microtubule stabilization. Alterations in Tau expression have been implicated in many pathologies, including neurodegenerative disorders and, more recently, certain forms of cancer such as glioblastoma, where aberrant Tau expression has been reported. The exploration and development of novel Tau-targeting agents remain in a vibrant field of research due to the urgent need for effective treatments against these Tau-dependent diseases. This review focuses on flavonoids and their role in modulating Tau function. We will begin with an overview of flavonoid classes and structures. Subsequently, we examine how flavonoids influence Tau function through both direct and indirect mechanisms, alongside key pathological Tau alterations, including liquid-liquid phase separation and aggregation. Flavonoids show promise in inhibiting Tau aggregation, but their low bioavailability limits therapeutic use. In this regard, we will outline many approaches to overcome this issue through structural modifications and nano-delivery systems to improve targeting and release of flavonoids in tissue. Finally, we highlight recent advances in the rational design of Tau-targeting agents based on flavonoid scaffolds, with particular emphasis on thiazoloflavonoids explored in GBM models. Our synthesis of current knowledge positions flavonoids as a versatile chemical platform, offering a viable path for Tau-directed therapies in neurodegenerative and oncogenic contexts.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100309"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568204","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}