European Journal of Medicinal Chemistry Reports最新文献

{"title":"Imidazole‒sulfonamide hybrid conjugate: A privilege scaffold with significant therapeutic potential","authors":"Riham M. Bokhtia","doi":"10.1016/j.ejmcr.2025.100321","DOIUrl":"10.1016/j.ejmcr.2025.100321","url":null,"abstract":"<div><div>Combining two or more biologically active moieties in a single structure recently became one of the most proposed concepts that have been adopted in drug development process. Enhanced efficacy, limited side effects and declined drug resistance are the main features of molecular hybridization approach. Both imidazole and sulfonamide cores are valuable pharmacophores and precious structural motifs of highly anticipated medicinal interest that grabbed researchers’ attention in the last few years and could serve as lead candidates with prodigious antibacterial, antifungal, antiviral, anticancer, anti-inflammatory, anticholinesterase, antioxidant and antidiabetic significance. Imidazole tethered sulfonamides utilized a shotgun strategy through binding to different sites on receptor, hitting multiple targets and exhibiting synergized therapeutic potential, dual inhibitory activity against various diseases including drug-resistant forms with diminished adverse reactions. This comprehensive review focuses on the fruitful influence of connecting these two scaffolds in a single hybrid molecule and outlines the promising biological importance of some imidazole‒sulfonamide conjugates as multitarget‒directed ligands (MTDLs) in terms of structure‒activity relationships.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"16 ","pages":"Article 100321"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920795","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":"N-Acylhydrazones: applications and advances in drug discovery","authors":"Giorgio Antoniolli ,&nbsp;Gabriel Rodrigues de Moraes ,&nbsp;Caterina Deruvo ,&nbsp;Cosimo Damiano Altomare ,&nbsp;Fernando Coelho ,&nbsp;Modesto de Candia","doi":"10.1016/j.ejmcr.2025.100317","DOIUrl":"10.1016/j.ejmcr.2025.100317","url":null,"abstract":"<div><div><em>N</em>-Acylhydrazones (NAHs) represent a structurally versatile and pharmacologically active class of compounds widely explored over last two decades in medicinal chemistry. Characterized by the presence of both hydrazide and imine functionalities, NAHs exhibit a rich spectrum of biological activities, including anti-inflammatory, antimicrobial, antitubercular, antiprotozoal, anticancer, and antiviral effects, as showed by a number of approved drugs (nitrofurazone, nitrofurantoin, carbazochrome, nifuroxazide, dantrolene, and azumolene) containing the NAH framework. Although discussion about toxicity, and efficacy of NAH-based drugs, several derivatives have been developed as a strategy to overcome failure and resistance in drug discovery. Indeed, in the NAH derivatives key physicochemical properties (lipophilicity/solubility, hydrogen-bonding property, and geometric or conformational isomerism) can easy modulated, to enhance their ability to generate bioactive small-molecules. In this review, by considering the PubMed, Scopus, Web of Science, and Google Scholar databases, we would provide a comprehensive current landscape of the therapeutic potential in drug-design and the state of the art of NAH progresses in pharmaceutical research.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"16 ","pages":"Article 100317"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145787344","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":"Exploiting the synergy between computational and experimental biophysics for efficient cancer drug development","authors":"Ana Álvarez-Mena ,&nbsp;Mélanie Berbon ,&nbsp;Carmelo Di Primo ,&nbsp;Rebeca Garcia-Fandino ,&nbsp;Ángel Piñeiro ,&nbsp;Carlos Fernandez-Lozano ,&nbsp;Hugo A.L. Filipe ,&nbsp;Birgit Habenstein","doi":"10.1016/j.ejmcr.2025.100320","DOIUrl":"10.1016/j.ejmcr.2025.100320","url":null,"abstract":"<div><div>Targeted cancer therapies have revolutionized oncology by developing treatments that specifically target cancer cells, reducing side effects. However, traditional drug discovery approaches are often hindered by high costs, long timelines, and low success rates. To address these challenges, the combination of computational and experimental biophysical techniques has become a highly effective approach. Molecular modeling methods, such as docking, molecular dynamics simulations, and virtual screening, enable <em>in silico</em> identification and optimization of drug candidates, while experimental biophysical techniques like NMR, SPR, and BLI validate molecular structures, binding interactions and affinities. This combined approach enhances the precision and efficiency of drug discovery, enabling progress in targeting oncogenic mutations, disrupting protein-protein interactions, and advancing drug repurposing efforts. Despite its potential, several challenges remain, including predictive limitations in computational models, experimental reproducibility, and the complexity of integrating diverse datasets. Future advances, particularly in artificial intelligence-driven methodologies, high-throughput screening, and drug repurposing, hold great potential to accelerate the development of innovative and effective cancer therapies.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"16 ","pages":"Article 100320"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145734033","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":"Inhibition of ginsenoside Re on pulmonary fibrosis induced by bleomycin in mice: Involved in modulating the CX3CL1/CX3CR1 axis","authors":"Zhaoqin Wen ,&nbsp;Huiyun Yang ,&nbsp;Hong Ling ,&nbsp;Huicai Lin ,&nbsp;Xiaoyan Chen ,&nbsp;Wan-Lan Shi ,&nbsp;Yongxiang Song ,&nbsp;Jiang Deng","doi":"10.1016/j.ejmcr.2025.100319","DOIUrl":"10.1016/j.ejmcr.2025.100319","url":null,"abstract":"<div><div>Pulmonary fibrosis (PF) is a common pathological feature of a variety of diffuse, progressive and irreversible pulmonary interstitial diseases, and effective therapeutic agents are currently lacking. Our previous study found that the total ginsenosides can improve pulmonary fibrosis induced by bleomycin in mice. Ginsenosides Re (G-Re) is one of the most abundant active ingredients in total ginsenosides and has a variety of pharmacological activities. This study investigated the inhibitory effect and mechanism of Re on pulmonary fibrosis in mice induced by bleomycin. The effects of G-Re on pulmonary fibrosis were evaluated using lung function measurement, pathological analysis, and detection of deposition of extracellular matrix (ECM). To investigate the mechanisms underlying the anti-pulmonary fibrosis effects of G-Re, chemokine CX3C ligand 1 (CX3CL1) and receptor 1 (CX3CR1), transforming growth factor beta 1 (TGF-β1), mitogen-activated protein kinase 1/2 (MEK1/2), extracellular signal-regulated kinase1/2 (ERK1/2), matrix metalloproteinase 2 (MMP2), and tissue inhibitor of metalloproteinases-1 (TIMP-1) in lung tissues were detected by molecular biology techniques, immunofluorescence and immunohistochemistry. Treatment with G-Re ameliorated pulmonary fibrosis in mice induced by bleomycin. In addition, it downregulated the levels of CX3CL1, CX3CR1, TGF-β1, MEK1/2, and MMP2. It upregulated the level of TIMP-1. These findings indicate that G-Re exerts protective effects against pulmonary fibrosis, likely through suppression of the CX3CL1/CX3CR1 axis and coordinated regulation of the ERK 1/2 signaling pathway and matrix metalloproteinases (MMPs), leading to reduced alveolar basement membrane injury and diminished extracellular matrix (ECM) accumulation in murine lung tissue.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"16 ","pages":"Article 100319"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145734031","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":"Synthetic developments and biological insights of 1,2,3-triazoles: Unravelling scope for drug discovery","authors":"Glanish Jude Martis,&nbsp;Sowmya Maiya,&nbsp;Santosh L. Gaonkar","doi":"10.1016/j.ejmcr.2025.100315","DOIUrl":"10.1016/j.ejmcr.2025.100315","url":null,"abstract":"<div><div>1,2,3-Triazoles have emerged as instrumental heterocyclic scaffolds playing key role in the field of synthetic and medicinal chemistry. The recent advancements utilizing the evolving technologies and the subsequent development of various synthetic strategies have dragged the attention based on their merits when compared to those with classical methods. In this review, different synthetic methods such as metal-catalyzed cycloaddition and metal-free reactions have been discussed with their noteworthy results. Also, focussing on the eco-friendliness domain, reactions following the green principles have been included. The scope of click reactions is wide and their optimisations play a crucial role. Erstwhile, the biological activity of the potential medicinal targets has opened a wide-gateway for the future medicinal chemistry and chemical biology. The impact of potent triazoles in appropriate areas is inclined throughout the review having the coverage of past twelve years which would help researchers working on discovery chemistry and biology across the world.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"16 ","pages":"Article 100315"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145683307","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":"Chemistry and pharmacology of naamine and naamidine-type marine alkaloids: an update","authors":"Christian Bailly","doi":"10.1016/j.ejmcr.2026.100325","DOIUrl":"10.1016/j.ejmcr.2026.100325","url":null,"abstract":"<div><div>The marine alkaloids naamine A and naamidine A were first isolated from a calcareous sponge forty years ago. Since 1987, about 40 related natural products have been discovered in this series, including naamines A-G, isonaamines A-D, naamidines A-K, isonaamidines A-E, pyronaamidine, spironaamidine, and a few other derivatives. The family also includes related imidazole alkaloids such as leucettamines, clathridines, calcaridines, as well as metal-coordinated dimeric products (e.g. (naamidine A)₂-Zn and (naamidine J)₂-Cu). Altogether, they represent a group of ∼70 imidazole alkaloids all isolated from marine species. Efficient and versatile synthetic processes have been set up to access these products and to design structural analogues. At the pharmacological level, studies have revealed the interest of these products to combat fungal and viral infections, and to treat certain cancers. A complete overview of these imidazole alkaloids, their chemistry, pharmacological properties and mechanisms of action is presented here. In several cases, key molecular targets have been identified, thus facilitating the structure-guided design of analogues and the identification of more potent synthetic analogues. Encouraging data have been reported with a naamidine A-based cream to treat mycosis, and with naamine A derivatives to viral (TMV) infections. In the naamidine J series, potent anticancer derivatives targeting key molecular targets (CSE1L, FDX1, PD-L1) have been characterized. Altogether, the analysis shed light on this family of marine alkaloids of prime medicinal interest, with the objectives to encourage further researches into their mechanism of action and bioactivities.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"16 ","pages":"Article 100325"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146169989","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":"Mechanisms of Panax notoginseng in the treatment of vascular disease: A review and preliminary analysis","authors":"Yunqi Zhang ,&nbsp;Jingyu Wang ,&nbsp;Liang Zhou ,&nbsp;Xiao Sun ,&nbsp;Yixin Wang ,&nbsp;Xiaobo Sun ,&nbsp;Yun Luo","doi":"10.1016/j.ejmcr.2026.100322","DOIUrl":"10.1016/j.ejmcr.2026.100322","url":null,"abstract":"<div><div><em>Panax notoginseng</em>, an essential Traditional Chinese Medicine (TCM), has been used to treat various vascular diseases, which are becoming widely recognized. However, there is a dearth of summary information regarding the therapeutic mechanism of <em>notoginseng</em> in the treatment of vascular diseases. This review provides an overview of the molecular mechanisms of <em>Panax notoginseng</em> in the treatment of various vascular diseases, including cardiovascular disease, cerebrovascular disease, diabetic microvascular complications, and ischemia reperfusion microvascular injury. Furthermore, a preliminary analysis utilizing network pharmacology is conducted to predict the potential illness spectrum of <em>notoginseng</em> in the treatment of vascular diseases, which provides reference for its further development and utilization in the future.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"16 ","pages":"Article 100322"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920793","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":"Fragment-based discovery of novel small molecule targeting human BAG3","authors":"Annagiulia Favaro ,&nbsp;Chiara Marchioro ,&nbsp;Martina Canton ,&nbsp;Thomas Stella ,&nbsp;Romeo Romagnoli ,&nbsp;Elena Mariotto ,&nbsp;Mattia Sturlese ,&nbsp;Giampietro Viola","doi":"10.1016/j.ejmcr.2026.100327","DOIUrl":"10.1016/j.ejmcr.2026.100327","url":null,"abstract":"<div><div>Bcl-2-associated athanogene 3 (BAG3) is a multifunctional co-chaperone protein that regulates apoptosis, autophagy, and proteostasis through interactions with HSP70 and other partners. Overexpression of BAG3 contributes to tumor cell survival, metastasis, and chemotherapy resistance, making it an appealing but challenging anticancer target due to its intrinsic disorder and lack of structural data. Here, we report a fragment-based drug discovery (FBDD) approach to identify novel small molecules targeting <em>human</em> BAG3. A fragment library of 783 compounds was screened using a thermal shift assay (TSA) against recombinant BAG3 expressed in mammalian cells, followed by hit validation through ligand-observed NMR (WaterLOGSY). Eleven fragments stabilized the protein, and seven were confirmed as binders. Among them, a 6-chloro-2-oxindole fragment (<strong>Fr1</strong>) exhibited the strongest interaction, with a dissociation constant (K_D) of 97.8 ± 11.1 μM. Structure–activity relationship (SAR) studies focused on maintaining the 6-chloro-2-oxindole core and optimizing substitutions at position 3, identified derivative <strong>7</strong> as a promising lead. Derivative <strong>7</strong> bound BAG3 with improved affinity (K_D ≈ 22 μM), as confirmed by grating-coupled interferometry, and displaced <strong>Fr1</strong> in competition NMR assays. This work demonstrates the feasibility of applying FBDD to intrinsically disordered and structurally unresolved proteins such as BAG3, providing a validated chemical starting point for the development of selective BAG3 inhibitors. These findings expand the druggability landscape of BAG3 and highlight fragment-based methodologies as powerful tools to explore protein–protein interaction targets previously considered intractable.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"16 ","pages":"Article 100327"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146170078","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":"Naringin exhibits adaptogen-like and neuroprotective effects on mice under chronic stress, reversing cortical neuroinflammation and neurodegeneration","authors":"Vivian O. Ojiakor ,&nbsp;Benneth Ben-Azu ,&nbsp;Elizabeth Finbarrs-Bello ,&nbsp;Emmanuel A. Esom ,&nbsp;Chike P. Anibeze ,&nbsp;Emeka G. Anyanwu","doi":"10.1016/j.ejmcr.2026.100323","DOIUrl":"10.1016/j.ejmcr.2026.100323","url":null,"abstract":"<div><div>Chronic unpredictable mild stress (CUMS) induces impairment in cortical functional connectivity, which plays an important role in depression and anxiety. It remains unclear if naringin, a natural adaptogen with antidepressant and anxiolytic effects, reverses CUMS-induced depression by normalizing cortical dysfunction. Therefore, this study investigated the adaptogen-like anti-anxiety and antidepressant effects of naringin on mice subjected to CUMS and the underlying mechanisms in the prefrontal cortex (PFC). Adult male Swiss mice (n = 9/group) received daily intraperitoneal injections of saline (10 mL/kg) for control and CUMS, naringin (2.5, 5, and 10 mg/kg), or fluoxetine (10 mg/kg), enduring CUMS for 21 days. Mice were assessed for depression and anxiety via neurobehavioural tests and neurochemical, biochemical and histochemical evaluations in the PFC. The hypothalamic-pituitary-adrenal (HPA) axis was measured by adrenal weight, serum corticosterone, and glucose levels. Naringin treatment reduced CUMS-induced depression, evidenced by higher sucrose consumption and decreased immobility in tests. It also alleviated anxiety-like behaviours in the elevated-plus maze and open-field tests. These effects correlated with lower corticosterone, serum glucose, and adrenal gland size. Naringin increased cortical antioxidant levels while reducing CUMS-induced lipid/nitrergic peroxidation and TNF-α and IL-1β. Both naringin and fluoxetine boosted serotonin, dopamine, and norepinephrine release in the PFC. Additionally, naringin countered CUMS-induced astrogliosis by lowering glial fibrillary acidic protein and upregulating brain-derived neurotrophic factor, with reduced pyknosis in the PFC. Naringin's antidepressant/anxiolytic effects stem from inhibiting inflammation, oxidative stress, enhancing HPA function, monoamine release, and astrocytic activity in the mouse PFC.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"16 ","pages":"Article 100323"},"PeriodicalIF":0.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022597","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, bioactivity and docking studies of chrysin derivatives as iNOS inhibitors","authors":"Federica Falbo ,&nbsp;Jessica Ceramella ,&nbsp;Domenico Iacopetta ,&nbsp;Nicola Gambacorta ,&nbsp;Daniela Trisciuzzi ,&nbsp;Orazio Nicolotti ,&nbsp;Michele De Luca ,&nbsp;Martina Chieffallo ,&nbsp;Anna Ramunno ,&nbsp;Daniela Bonofiglio ,&nbsp;Lorenza Improta ,&nbsp;Francesca Aiello ,&nbsp;Maria Stefania Sinicropi","doi":"10.1016/j.ejmcr.2025.100301","DOIUrl":"10.1016/j.ejmcr.2025.100301","url":null,"abstract":"<div><div>Endothelial dysfunction, mainly linked to ionic channel malfunctions, is a key mechanism in the pathogenesis of different vascular disorders including hypertension and atherosclerosis. Several studies confirm a strong correlation between endothelial dysfunction, inflammation and oxidative stress. Regular consumption of antioxidant polyphenol-rich foods has been linked to a reduction in cardiovascular morbidity and mortality. The flavone chrysin, a known Ca_v1.2 channel inhibitor, was selected in this work as lead compound to generate a library of its derivatives evaluated for their antioxidant and anti-inflammatory properties by means of <em>vitro</em> and cell-based assays. Among them, the best one resulted in the 8-nitrochrysin (<strong>1i</strong>). Molecular docking revealed that the nitro group plays a critical role in enhancing the binding mode toward iNOS by facilitating the formation of additional polar interactions compared to chrysin. LogP values of chrysin derivatives were also experimentally determined <em>via</em> spectrophotometric method to evaluate the impact of the chemical modifications with respect to the parent compound.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100301"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265788","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}