European Journal of Medicinal Chemistry Reports最新文献

{"title":"Development of highly potent and selective oncogenic KRASG12D PROTAC degraders","authors":"Yaqiu Mao ,&nbsp;Pengli Wei ,&nbsp;Ting Wei ,&nbsp;Yalei Wang ,&nbsp;Zhenze Qi ,&nbsp;Xu Cai ,&nbsp;Changkai Jia ,&nbsp;Zhiyuan Zhao ,&nbsp;Bingkun Li ,&nbsp;Min Qiao ,&nbsp;Yaxin Zou ,&nbsp;Zhihui Mu ,&nbsp;Xiaofang Lei ,&nbsp;Tingting Yang ,&nbsp;Shiyang Sun ,&nbsp;Xuesong Feng ,&nbsp;Pengyun Li ,&nbsp;Zhibing Zheng","doi":"10.1016/j.ejmcr.2025.100296","DOIUrl":"10.1016/j.ejmcr.2025.100296","url":null,"abstract":"<div><div>As a key driver of tumorigenesis and cancer development, the KRAS^G12D mutation is ubiquitous existed in KRAS-associated malignancies, highlighting the urgent clinical need for effective KRAS^G12D targeting drugs. In this study, through rational design and multiple cell type-based antiproliferative evaluation, we identified a novel KRAS^G12D inhibitor, <strong>Y-I-1</strong>, which demonstrated remarkable anti-cancer activity. Subsequent computational analyses including molecular dynamics (MD) simulations, binding free energy calculations, umbrella sampling, and protein-ligand docking revealed its excellent binding characteristics, rationalizing the observed potency. Building upon the structure of <strong>Y-I-1</strong>, we constructed proteolysis-targeting chimera (PROTAC) by conjugating it with different linker moieties and VH032. Among them, degrader <strong>Y-D-2</strong> potently and selectively exhibited nanomolar inhibitory IC₅₀, degradation DC₅₀ values, and more than 95 % maximum degradation (D_max) in KRAS^G12D-mutant cancer cells via ubiquitin proteasome-involving pathway, accompanied by nanomolar IC₅₀ efficiency for phosphorylated ERK (pERK) inhibition. Mechanistically, <strong>Y-D-2</strong> significantly induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, <strong>Y-D-2</strong> led to significant tumor growth inhibition in the GP2D xenograft model with well-tolerated dose-schedules with favorable PK properties. This study not only provides an important theoretical basis for the optimal design of KRAS^G12D degraders, but also highlights its potential for the treatment of KRAS^G12D-driven cancers.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100296"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922177","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":"Structure-activity study of oncocins modified with cationic polar moieties at the termini","authors":"Johan Storm Jørgensen ,&nbsp;Anita Wester ,&nbsp;Carina Sofia Silva Matias ,&nbsp;Lina Maria Cavaco ,&nbsp;Carina Vingsbo Lundberg ,&nbsp;Camilla Brolin ,&nbsp;Elnaz Harifi Mood ,&nbsp;Dorota Żabicka ,&nbsp;Magdalena Tomczak ,&nbsp;Malgorzata Urbas ,&nbsp;Fredrik Björkling ,&nbsp;Peter E. Nielsen ,&nbsp;Henrik Franzyk","doi":"10.1016/j.ejmcr.2025.100284","DOIUrl":"10.1016/j.ejmcr.2025.100284","url":null,"abstract":"<div><div>The critical emergence of antimicrobial resistance is aggravated by a pipeline deficient in novel antibiotic classes against Gram-negative pathogens. Proline-rich antimicrobial peptides (PrAMPs) are attractive starting points for novel antibiotics, capable of targeting Gram-negative pathogens. Here, we explored a series of oncocin analogs, which were modified with bacteria-penetrating moieties to promote transporter-independent antibacterial activity. Elongation with arginine-rich motifs conferred 2- to 8-fold improved potency against the Gram-negative <em>Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa</em> and <em>Acinetobacter baumannii</em>. The highest degree of enhancement was seen for <em>K. pneumoniae</em>, in which the most active analogs had minimal inhibitory concentrations of 0.25 μg/mL (∼0.05 μM).</div><div>Notably, antibacterial activity proved considerably less dependent on the inner-membrane peptide transporter SbmA, being the main transporter involved in internalization of PrAMPs. Permeabilization experiments showed that these cationic modifications did not alter the original intracellular mode of action of oncocin itself towards a membrane-disruptive mechanism for these analogs. Importantly, their effect on human cell viability remained low for the best analogs (i.e., below 5 % hemolysis at 400 μg/mL and IC₅₀ values ≥ 1280 μg/mL in HepG2 cells). Moreover, the frequencies of existing resistance of best analogs in <em>E. coli</em> and <em>K. pneumoniae</em> were low (i.e., 1-5 × 10⁻¹⁰). Finally, two analogs were tested in a mouse peritonitis model with <em>E. coli</em>, while one analog was tested in a model with <em>K. pneumoniae</em>. This showed efficacy comparable to that of colistin in the <em>E. coli</em> model, while a lower efficacy than that of colistin was seen in the <em>K. pneumoniae</em> model.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100284"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144563102","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":"Therapeutic potential of Bowman-Birk inhibitors in various disorders: A comprehensive review","authors":"Masoud Hashemzaei ,&nbsp;Majid Nimrouzi ,&nbsp;Mehdi Salehi ,&nbsp;Fatemeh Hosseinpour-Soleimani ,&nbsp;Amir Tajbakhsh ,&nbsp;Mohammad Hashem Hashempur","doi":"10.1016/j.ejmcr.2025.100310","DOIUrl":"10.1016/j.ejmcr.2025.100310","url":null,"abstract":"<div><div>Bowman-Birk Inhibitors (BBIs) are plant-derived serine protease inhibitors with diverse biological activities and significant therapeutic potential. Originally isolated from soybeans, BBIs have demonstrated potent anticancer effects that surpass those of other soy-derived agents. This review comprehensively examines the multifaceted therapeutic applications of BBIs, including their anticancer, anti-inflammatory, antimicrobial, and gastrointestinal protective properties. We explore the structural and stability features and evolutionary relationships that underpin BBIs’ unique dual-inhibitory activity against serine proteases. The molecular mechanisms through which BBIs exert their effects—such as modulation of key signaling pathways, immune regulation, and microbial membrane disruption—are also discussed. Advances in synthetic peptide mimics, exemplified by sunflower trypsin inhibitor-1 (SFTI-1), highlight opportunities for therapeutic optimization. Additionally, clinical trial data on Bowman-Birk Inhibitor Concentrate (BBIC), a BBI-enriched soybean extract, demonstrate safety and efficacy without neutralizing antibody development. This review synthesizes current insights into BBIs, underscoring their remarkable versatility and promising role in cancer prevention, inflammatory disease management, and antimicrobial therapy, while addressing ongoing challenges and future directions.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100310"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568205","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":"Protective effects of Sacha inchi meal protein hydrolysate against oxidative stress and endothelial dysfunction via MDA suppression and SOD activation in L-NAME-induced hypertensive rats","authors":"Pakaporn Sa-nguanpong ,&nbsp;Paweena Wetprasit ,&nbsp;Usana Chatturong ,&nbsp;Krongkarn Chootip ,&nbsp;Napapas Kantip ,&nbsp;Worasit Tochampa ,&nbsp;Khanitta Ruttarattanamongkol ,&nbsp;Tippaporn Bualeong","doi":"10.1016/j.ejmcr.2025.100297","DOIUrl":"10.1016/j.ejmcr.2025.100297","url":null,"abstract":"<div><div>Endothelial dysfunction and oxidative stress are central contributors to hypertension. Sacha inchi meal protein hydrolysate (SIPH) is recognized for its strong antioxidant activity and potential cardiovascular benefits. This study investigated the protective effects of SIPH on endothelial function and oxidative stress in rats with L-NAME (LN)-induced hypertension. Acute oral toxicity testing showed an LD₅₀ greater than 5000 mg/kg, classifying SIPH as low hazard (Category 5). Male Sprague-Dawley rats received LN (40 mg/kg) and were treated orally with SIPH (100, 300, or 500 mg/kg), captopril (5 mg/kg), or SIPH (500 mg/kg) combined with captopril (2.5 mg/kg) for five weeks. Blood pressure was monitored weekly and validated by carotid artery cannulation. Endothelial function was assessed by vasorelaxation responses to acetylcholine (ACh) and sodium nitroprusside (SNP) in isolated aortic rings, while serum malondialdehyde (MDA) and superoxide dismutase (SOD) activity were measured as markers of oxidative stress. LN administration elevated blood pressure impaired ACh-induced vasorelaxation, increased MDA, and reduced SOD activity. SIPH at 500 mg/kg significantly reduced blood pressure, restored endothelial-dependent relaxation, decreased lipid peroxidation, and enhanced antioxidant defense. Notably, the combination of SIPH with captopril exerted synergistic antihypertensive effects, producing greater improvements in vascular reactivity and oxidative balance than either treatment alone. These findings demonstrate that SIPH is a potent vascular protector, acting through synergistic antihypertensive, vasodilatory, and antioxidant mechanisms. Its properties position SIPH as a promising natural dietary intervention for mitigating hypertension and preserving endothelial function.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100297"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044692","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":"Aurones as versatile enzyme Inhibitors: Recent advancements, structural insights, mechanisms, and therapeutic potential","authors":"Bhavna Saroha ,&nbsp;Gourav Kumar ,&nbsp;Suresh Kumar","doi":"10.1016/j.ejmcr.2025.100280","DOIUrl":"10.1016/j.ejmcr.2025.100280","url":null,"abstract":"<div><div>Aurones belong to the flavonoid-based heterocyclic class of plant origin and are full of therapeutic potential. Characterized by their unique benzofuranone core structure and α,β unsaturated carbonyl group, aurones possess exceptional structural adaptability and electronic characteristics, making them excellent candidates for enzyme targeting and promising agents for drug development. Recent research has highlighted their ability to inhibit key enzymes, including cholinesterase, cathepsin B, monoamine oxidase, cyclooxygenase, and various digestive enzymes. This demonstrates their potential in treating cancer, neurodegenerative diseases, and metabolic disorders associated with the overexpression of these enzymes. The ability to functionalize the aurone scaffold further enhances its adaptability for selective and potent enzyme targeting. This review examines the structural features of aurones, their enzyme-inhibitory effects, an overview of their molecular mechanisms, and the structure-activity relationships (SAR) underlying their enzyme inhibition, supported by computational approaches. Although several review articles have addressed the synthetic and general biological profile of aurones, none have specifically focused on their enzyme inhibitory potential, which is the central theme of this review. This review offers a strong foundation and rationale for the design, synthesis, and optimization of novel aurone-based compounds aimed at achieving desirable therapeutic outcomes by targeting specific enzymes.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100280"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330496","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":"The impact of secondary site interactions on the binding specificity of bitopic dopamine D2/D3 receptor ligands","authors":"Attila Egyed ,&nbsp;Dóra Judit Kiss ,&nbsp;Zsófia Pável ,&nbsp;Keve Rajna ,&nbsp;Supriya A. Gaitonde ,&nbsp;Mariam Dubiel ,&nbsp;María Isabel Loza ,&nbsp;Edina Szűcs ,&nbsp;Éva Borbély ,&nbsp;Zsófia Hajna ,&nbsp;Grzegorz Satala ,&nbsp;Márton Vass ,&nbsp;Pál Szabó ,&nbsp;Katalin Jósvay ,&nbsp;Andrzej J. Bojarski ,&nbsp;Holger Stark ,&nbsp;Zsuzsanna Helyes ,&nbsp;Erika Pintér ,&nbsp;Michel Bouvier ,&nbsp;György M. Keserű","doi":"10.1016/j.ejmcr.2025.100302","DOIUrl":"10.1016/j.ejmcr.2025.100302","url":null,"abstract":"<div><div>Dysfunction of dopamine receptors and interruption of normal dopaminergic signaling have been linked to severe neuropsychiatric diseases such as schizophrenia, Parkinson's disease and depression. Although these receptors are among the most drug-targeted families of GPCRs, designing compounds with subtype-specific pharmacological profile remains challenging due to the structural similarities among the subtypes of the family. Considering the structural moieties of cariprazine, a prototypic drug with D₃ receptor (D₃R) preference, we report a library of bitopic analogues to explore how the orthosteric and secondary binding motifs, coupled with different linkers, affect D₂R/D₃R selectivity and activity. Compounds with promising dopamine receptor selectivities and binding affinities were further characterized on a GPCR panel and in functional assays. Our efforts resulted in an advanced lead compound (<strong>20b</strong>) with improved D₃R and 5-HT_2AR, as well as decreased D₂R and 5-HT_1AR potencies (EC₅₀) compared to cariprazine. The cleaner receptor profile of this compound retained activities for the most important antidepressant mechanisms that were confirmed by reducing the depression-like behavior in mice.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100302"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412593","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":"Molecules with alkyne fragment in medicinal chemistry: The path from neurotoxins to drugs","authors":"Nataliya Zelisko ,&nbsp;Roman Lesyk","doi":"10.1016/j.ejmcr.2025.100294","DOIUrl":"10.1016/j.ejmcr.2025.100294","url":null,"abstract":"<div><div>In this comprehensive review, we explore a diverse array of highly promising compounds, categorized based on their pharmacological properties, origins, and synthetic methodologies, to highlight the critical role of alkyne functionalities in advancing medicinal chemistry. Our analysis underscores the unique contributions of acetylene-containing compounds, emphasizing their structural significance and therapeutic potential.</div><div>The remarkable versatility of acetylene-bearing molecules is evident in their wide-ranging biological activities, which position them as exceptional candidates for drug development. Extensive studies compiled in this review demonstrate that incorporating an acetylene group into molecular frameworks significantly enhances bioactivity. Numerous naturally occurring alkynes exhibit potent antibacterial, antifungal, and anticancer effects. Notably, compounds featuring a propargylamine group are established inhibitors of monoamine oxidase (MAO) and cholinesterases (ChEs). Additionally, a range of alkyne derivatives shows promise as H3-receptor antagonists, offering potential treatments for conditions such as epilepsy, depression, schizophrenia, Parkinson's disease, Alzheimer's disease, sleep disorders, attention deficit hyperactivity disorder, and various inflammatory and gastrointestinal disorders. Acetylene-containing compounds also play a role in anti-HIV therapies, with certain synthetic steroids falling within this class. Furthermore, alkynes are integral to multi-target-directed ligand (MTDL) strategies, broadening their therapeutic applications.</div><div>A particular focus of this review is the compelling anticancer potential of MAO inhibitors, which have garnered significant attention from pharmaceutical companies for their efficacy against prostate cancer, Hodgkin lymphoma, glioma brain tumors, non-small cell lung cancer, A-2058 melanoma cell lines, and acute myeloid leukemia. This has spurred interest in drug repurposing, establishing these compounds as a cornerstone of innovative therapeutic development.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100294"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895362","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":"Towards \"unmakable\" psychedelics: SAR exploration of psilocin analogs obtained by a HATU-mediated amide coupling strategy","authors":"Judith Stirn ,&nbsp;Raphael Berger ,&nbsp;Harald Hübner ,&nbsp;Peter Gmeiner ,&nbsp;Christian D. Klein","doi":"10.1016/j.ejmcr.2025.100278","DOIUrl":"10.1016/j.ejmcr.2025.100278","url":null,"abstract":"<div><div>4-Hydroxytryptamines such as psilocin and its prodrug psilocybin are of considerable current interest for innovative antidepressant and other neuropsychiatric treatments. We here present a synthetic route towards 4-hydroxytryptamines displaying a high versatility for SAR exploration at the aliphatic nitrogen. The core concept is to apply HATU-mediated amide couplings to a readily accessible and stable <em>N</em>^<em>1</em>-Boc-indole-3-glyoxylic acid precursor followed by <em>N</em>-deprotection under mild conditions. We illustrate the versatility of this approach by the synthesis of various sterically hindered, conformationally constrained, chiral, and electron-deficient 4-hydroxytryptamines, including closely related congeners of iprocin. In addition, the structure-activity relationships of the obtained compounds are explored with a focus on their interaction with the serotonin receptors 1A and 2A (5-HT_1/2A). An increase in steric bulk at the aliphatic nitrogen appears to be detrimental to the affinity to the 5-HT_2A receptor, whereas azetidinyl tryptamines bearing a terminal aryl moiety demonstrated remarkably high affinity.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100278"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231740","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":"Structure optimization at position five of 4-thiazolidinone resulted in new potent PIM1 kinase inhibitors with apoptosis induction and caspase 3/7 activation capabilities for combating colorectal cancer","authors":"Ahmed K. Al-Kubeisi ,&nbsp;Saad R. El-Zemity ,&nbsp;Marwa M. Abu-Serie ,&nbsp;Aly A. Hazzaa ,&nbsp;Mostafa M.M. El-Miligy","doi":"10.1016/j.ejmcr.2025.100279","DOIUrl":"10.1016/j.ejmcr.2025.100279","url":null,"abstract":"<div><div>New thymol – 5-phenylthiazolidin-4-one hybrids were synthesized aiming to interact with the lipophilic flexible p-loop of PIM kinase active site via induced-fit binding mode to increase affinity hence anticancer activity against colorectal cancer (CRC). All target compounds were screened for their cytotoxicity against normal human lung fibroblasts and anticancer activity against CRC Caco-2 cell lines. <strong>6c</strong> and <strong>6e</strong> exhibited the highest anticancer activity at doses less than their EC₁₀₀ on normal human cells. In addition, <strong>6c</strong> and <strong>6e</strong> were further tested against liver cancer cell line (HepG-2) and breast cancer cell line (MCF-7) and proved their potent anticancer activities. Furthermore, both induced apoptosis in Caco-2 cell lines by 39 and 55 % and enhanced caspase 3/7 activation by 43 and 65 %, respectively. Besides, <strong>6c</strong> and <strong>6e</strong> revealed <em>in vitro</em> inhibitory activity against PIM1 kinase more than PIM2 kinase. Furthermore, induced fit docking and molecular dynamics simulation of <strong>6c</strong> and <strong>6e</strong> predicted enhanced PIM1 kinase activity via interaction to flexible p-loop. Moreover, both could act as PIM1 kinase competitive non-ATP mimetics as they interacted with Lys67.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100279"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231741","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":"Glaucumolides C-P, cembrane-type diterpenoids from the marine soft coral Sarcophyton glaucum with potential attenuating activities against IgAN nephropathy","authors":"Kang Zhou ,&nbsp;Jian Huang ,&nbsp;Hongli Jia ,&nbsp;Pianpian Wang ,&nbsp;Bin Wang ,&nbsp;Wei Cheng ,&nbsp;Wenhan Lin","doi":"10.1016/j.ejmcr.2025.100287","DOIUrl":"10.1016/j.ejmcr.2025.100287","url":null,"abstract":"<div><div>Cembranoids represent a class of diterpenes, featuring a cyclotetradecadiene backbone substituted by an isopropyl residue and three methyl groups with diverse subtypes and a panel of bioactivities. In this study, molecular networking-based metabolomic analysis revealed the soft coral <em>Sarcophyton glaucum</em> containing a chemical profile of cembrane-type diterpenes. Targeted isolation of the diterpene-enriched fractions resulted in the isolation of 14 undescribed cembranoids, namely glaucumolides C-P (<strong>1</strong>–<strong>14</strong>). Their structures were determined by extensive spectroscopic data in association with the X-ray diffraction and electronic circular dichroism (ECD) data for configurational assignments. All analogs featured an unsaturated γ-lactone in the backbone. Glaucumolide M and metabolite-A exhibited significant inhibition against the proliferation of lipopolysaccharide (LPS)-induced DAKIKI cells, and upregulated the expression of mRNA of C1GalT1 and its chaperone Cosmc in DAKIKI cells dose-dependently. Those findings suggest glaucumolides to be potential to prevent imunoglobulin A (IgA) nephropathy.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100287"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144722338","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}