Anti-cancer agents in medicinal chemistry最新文献

{"title":"Nucleobase Ionic Liquids (NBILs) Induced Apoptosis via Caspase 3 Activation and in silico Regulation of the IRE1a Pathway in Pancreatic Cancer PANC-1 Cells.","authors":"Pradnya Patil, Prakash Bansode, Gaurang Telang, Smriti Mishra, Deepti Kurhe, Dipak Mali, Namdeo Jadhav, Dilip Dagade, Dattaprasad Pore, Gajanan Rashinkar","doi":"10.2174/0118715206415118251205220038","DOIUrl":"https://doi.org/10.2174/0118715206415118251205220038","url":null,"abstract":"<p><strong>Introduction: </strong>Globally rising incidences of pancreatic cancer, a leading cause of death, have made it imperative to explore new chemotherapeutic agents, such as ionic liquids (ILs), as an emerging class of anticancer agents. Nucleobase ionic liquids (NBILs) have shown great promise against pancreatic cancer PANC-1 cells. This study aims to synthesize purine and pyrimidine nucleobase ionic liquids (NBILs) and evaluate their in vitro anticancer activity on PANC-1 cells to gain valuable insights into the anticancer potential of NBILs.</p><p><strong>Methods: </strong>Comprehensive in vitro studies, including flow cytometric apoptosis analysis, reverse transcription polymerase chain reaction (RT-PCR), gene expression studies, and molecular docking analysis, were performed to demonstrate the potent anticancer effects of NBILs.</p><p><strong>Results: </strong>A series of nucleobase ionic liquids (NBILs) was synthesized using a multi-step protocol. Significant anti-pancreatic cancer activity was observed for the synthesized NBILs against PANC-1 cells, with compound 14b showing high expression of CASP3 and a high percentage of apoptosis.</p><p><strong>Discussion: </strong>Molecular mechanism and in silico studies demonstrated remarkable anti-pancreatic cancer activity of NBILs via activation of CASP3 and regulation of the IRE1a pathway. The research highlights the future potential for utilizing NBILs against pancreatic cancer PANC-1 cells.</p><p><strong>Conclusion: </strong>NBILs displayed significant anti-pancreatic cancer activity through apoptosis induction via activation of Caspase 3 and in silico regulation of the IRE1a pathway in pancreatic cancer PANC-1 cells.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832751","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":"CAF Heterogeneity in Ovarian Cancer: Implications for Chemoresistance and Treatment Strategies.","authors":"Sambasivam Gopinath, Pavithra Balakrishnan, Yamini Muli, Jubilee Ramasamy, Saranya Puniyakotti, Nithya Varadarajan, Ramaiyan Velmurugan","doi":"10.2174/0118715206434395260409095604","DOIUrl":"https://doi.org/10.2174/0118715206434395260409095604","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer-Associated Fibroblasts (CAFs) are key players in the tumor microenvironment (TME) of ovarian cancer, influencing progression and chemoresistance. Their heterogeneous subtypes contribute distinctly to immune evasion, extracellular matrix (ECM) remodelling, and drug resistance.</p><p><strong>Methods: </strong>This review synthesizes evidence from recent single-cell and proteomic analyses to delineate CAF subtypes, including myCAFs, iCAFs, and apCAFs, and their associated gene signatures (e.g., VCAN, SULF1, COL11A1, CXCL12). The relationship between CAF-mediated pathways and resistance to platinum-based chemotherapies is explored.</p><p><strong>Results: </strong>High expression of CAF-associated genes correlates with platinum resistance in ovarian cancer. VCAN enhances ECM stiffness and immune suppression; SULF1 alters ECM sulfation, affecting drug uptake; COL11A1 activates Src/Akt pathways leading to EMT; and CXCL12 triggers Wnt/β-catenin signalling, increasing resistance. These mechanisms collectively impair treatment efficacy.</p><p><strong>Discussion: </strong>The dynamic and plastic nature of CAFs presents both a challenge and an opportunity in cancer therapy. While some CAF subsets promote chemoresistance, others may exert tumor-suppressive effects. This duality underscores the importance of precise molecular profiling to distinguish between pro-tumor and antitumor CAF populations. Current data suggest that therapeutic approaches targeting CAF-specific genes or pathways, particularly those influencing ECM remodelling and survival signalling, could significantly enhance the efficacy of standard chemotherapy. Personalized treatment strategies that selectively deplete or reprogram tumor- promoting CAFs while preserving supportive stromal elements may improve patient outcomes.</p><p><strong>Conclusion: </strong>Targeting specific CAF subtypes and their molecular pathways offers promise for overcoming chemoresistance. Future therapies should focus on eliminating tumor-promoting CAFs while preserving or reprogramming tumor-suppressive ones.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832761","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":"MicroRNA-21 in Cancer and Fibrosis: Molecular Mechanisms and Therapeutic Progress.","authors":"Anushka Sharma, Awaneet Kaur, Javed Khan, Himani Pandey","doi":"10.2174/0118715206442580260401101941","DOIUrl":"https://doi.org/10.2174/0118715206442580260401101941","url":null,"abstract":"<p><p>MicroRNA-21 (miR-21) is a key regulator of gene expression involved in cancer progression and fibrosis. Its dysregulation promotes cell proliferation, resistance to apoptosis, Epithelial-Mesenchymal Transition (EMT), and Extracellular Matrix (ECM) remodeling, making it one of the most widely studied oncomiRs and fibromiRs. Evidence shows that miR-21 contributes to tumor growth, metastasis, and fibrosis by suppressing tumor suppressors such as PTEN and PDCD4 and activating pro-fibrotic pathways, including TGF-β signaling. Its consistent dysregulation highlights its potential as a biomarker for diagnosis, prognosis, and treatment monitoring. Several therapeutic strategies, such as antagomiRs, locked nucleic acids (LNAs), CRISPR-based inhibition, and nanoparticle- or viral-mediated delivery systems, have shown promising preclinical results. Despite advances, challenges remain in translating miR-21 inhibition to clinical use. Key limitations include off-target effects, delivery inefficiencies, and context-dependent variability in miR-21 function. These issues hinder the development of safe and effective miR-21-targeted therapies. MiR-21 plays a central role in cancer and fibrosis and offers significant potential as both a biomarker and therapeutic target. Future research should focus on precision-based approaches, next-generation gene-editing technologies, and improved preclinical models to optimize miR-21 inhibition for clinical application. This review compiles and evaluates current literature on miR-21 biogenesis, regulation, functional roles, and therapeutic targeting across various cancers and organ-specific fibrotic disorders.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832847","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":"Overview of Spirooxindoline Scaffolds in Cancer Therapy.","authors":"Kamlesh Sharma","doi":"10.2174/0118715206433392260406050321","DOIUrl":"https://doi.org/10.2174/0118715206433392260406050321","url":null,"abstract":"<p><p>Spirooxindoline derivatives have emerged as promising scaffolds in cancer therapy due to their structural diversity and potent cytotoxic effects. This review summarizes progress in the structural design and biological assessment of spirooxindoline derivatives. Modifications at the oxindole and benzene rings markedly enhance potency and selectivity against key cancer cell lines such as HeLa, MCF-7, HepG2, and A549. Several derivatives, including spirooxindole-pyrrolidine hybrids, thiazolo-pyrrolidine-spirooxindolines, and dispirooxindolines, demonstrate superior activity compared with cisplatin and doxorubicin. Mechanistic studies reveal induction of apoptosis, inhibition of proliferation, and interactions with critical targets including EGFR, HER2, and p53. Emerging synthetic strategies, particularly multicomponent reactions and click chemistry, further expand the scope of these molecules. Collectively, current findings underscore their potential as anticancer agents and the importance of future in vivo and pharmacokinetic studies to advance clinical translation.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832798","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 Evaluation of the Methyl (Z)-2-(isothioureidomethyl)-2-pentenoate Hydrobromide: Antitumor Efficacy and Safety Profile in a Murine Melanoma Model.","authors":"Laura Sartori Assunção, Iara Fabrícia Kretzer, Ana Gabriela Rosa, Mariana Martins Vernaschi, Juliano Andreoli Miyake, Evelise Maria Nazari, Misael Ferreira, Marcus Mandolesi Sá, Tania Beatriz Creczynski-Pasa","doi":"10.2174/0118715206441663260216045255","DOIUrl":"https://doi.org/10.2174/0118715206441663260216045255","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Melanoma is a malignancy often resistant to conventional therapies, highlighting the need for novel agents that effectively target tumor progression and subdue apoptotic resistance. Isothiouronium salts have shown promising anticancer potential; however, their in vivo potential remains largely unexplored. This study aimed to evaluate the preclinical safety and antitumor efficacy of the isothiouronium derivative ISMF08.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;C57BL/6J mice underwent acute and repeated-dose toxicity studies to determine the maximum tolerated dose (MTD) of IS-MF08. Following MTD determination, melanoma-bearing mice inoculated with B16F10 cells were treated intraperitoneally with IS-MF08 for 10 days. Tumor growth, survival, body weight, hematological parameters, and histopathology of liver, kidneys, and tumor tissue were evaluated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The MTD was defined as 15 mg/kg. Repeated dosing with IS-MF08 at 12 mg/kg was well tolerated and promoted tumor growth inhibition (87%) and increased survival. Treatment also attenuated weight loss and tumor- induced anemia and leukocytosis. Histological analyses of tumors showed reduced neoplastic cell density and signs of collagen deposition. Mild histological changes in the liver and kidneys were observed at higher doses, along with an isolated increase in ALT levels and a slight increase in serum creatinine. In contrast, other liver enzymes (AST, ALT), TB, DB, total protein, albumin, and renal function markers remained within physiological limits.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;Preclinical evidence suggests that IS-MF08 is a promising candidate for further development as a multitargeted antineoplastic compound. It has demonstrated selectivity, tumor growth inhibition, and a manageable toxicity profile, positioning it as a potential therapeutic option for melanoma and possibly other solid tumors with similar resistance mechanisms. However, several limitations should be acknowledged. The antitumor activity of ISMF08 was evaluated in a single syngeneic mouse model (B16F10), which may not fully recapitulate the heterogeneity of human tumors. Furthermore, the lack of pharmacokinetic data and long-term toxicity assessments limits conclusions about the compound's safety over prolonged periods. Additionally, histopathological and hematological analyses have provided initial insights into the drug's tolerability. Future studies should expand the range of tumor models, explore immunological interactions, and incorporate molecular assays and bioavailability profiles to better elucidate the therapeutic potential and translational applicability of IS-MF08.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;IS-MF08 demonstrated robust antitumor activity with a safety profile. Despite the limitations of the present study, these findings support its continued development as a potential multi-target chemotherapeutic agent. Further studies are necessary to elucidate the ther","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832771","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":"Anticancer Potential of Eudesmanolides Derived from Sphagneticola trilobata against Colorectal Cancer, by Targeting β-catenin Signalling.","authors":"Remya Johny, Faisal Moossa Athikkavil, Sreekumar U Aiswarya, Amrutha A Nisthul, Meghna Sudhesh, Balan Abhijith, K A Krishnakumar, Ruby J Anto, Ravi S Lankalapalli, Smitha V Bava","doi":"10.2174/0118715206431960260123110937","DOIUrl":"https://doi.org/10.2174/0118715206431960260123110937","url":null,"abstract":"<p><strong>Introduction: </strong>The role of β-catenin signalling in the pathogenesis of Colorectal Cancer (CRC) is indisputable. In this study, we report the identification of a cytotoxic fraction that targets the β-catenin signalling axis in colorectal cancer cells.</p><p><strong>Methods: </strong>Chromatographic and spectrometric techniques were used for the isolation and phytochemical characterization of Eudesmanolides (EDS). Cell-viability assays, flow cytometry, fluorescent microscopy, immunoblot analysis, qRT-PCR, and in silico molecular docking studies were used to analyse the antitumor potential of EDS against CRC cells. Toxicological evaluation of EDS was conducted in Swiss albino mice.</p><p><strong>Results: </strong>We have isolated and characterized the bioactive fraction designated EDS, consisting of the eudesmanolides, namely wedelolide D and prostrolide A, from the Ethyl Acetate (EA) leaf extract of the plant Sphagneticola trilobata (S. trilobata). EDS was found to be highly efficacious against CRC cells and induced an apoptotic mode of cell death in different CRC cell lines. Delineation of the apoptotic pathway induced by EDS revealed extrinsic pathway activation and amplification of the apoptotic signals via the intrinsic pathway through truncated-BID. Molecular investigations revealed EDS-mediated inhibition of β-catenin signalling and PPAR-γ (peroxisome proliferator-activated receptor gamma) activation in HCT116 CRC cells.</p><p><strong>Discussion: </strong>Our study revealed that EDS induced strong apoptotic signals in CRC cells, initiated at the cell surface, resulting in apoptosis involving extrinsic and intrinsic mechanisms irrespective of the p53 status or molecular phenotype of CRC cells. In addition, PPAR-γ activation by EDS resulted in the suppression of β- catenin nuclear accumulation and the subsequent inhibition of proliferative and survival signalling. Moreover, EDS was found to be pharmacologically safe.</p><p><strong>Conclusion: </strong>To summarize, we demonstrate, with mechanism-based evidence, the chemotherapeutic efficacy of EDS, comprising the eudesmanolides, wedelolide D, and prostrolide A, derived from S. trilobata, against CRC. The potential of these lead-structures are worth exploring for their beneficial effects in combination with other therapeutic interventions.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832802","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":"Caffeic Acid Phenethyl Ester (CAPE) Inhibits Hepatocellular Carcinoma Growth and Angiogenesis via Vascular Endothelial Growth Factor Suppression: A Preclinical Evidence.","authors":"Lei Gong, Wenzhen Wang, Zenghua Deng, Nan Luo, Jirun Peng","doi":"10.2174/0118715206436841260123054356","DOIUrl":"https://doi.org/10.2174/0118715206436841260123054356","url":null,"abstract":"<p><strong>Introduction: </strong>Caffeic acid phenethyl ester (CAPE), a natural compound, has shown antitumor potential, but its efficacy and mechanism in hepatocellular carcinoma (HCC) require further validation, particularly in vivo. This study systematically investigated the antitumor efficacy and safety profile of CAPE against HCC through comprehensive in vitro and in vivo experiments.</p><p><strong>Methods: </strong>In vitro, the anti-proliferative effect of CAPE (0-160 μM) on the human HCC cell line Bel-7402 was evaluated using the CCK-8 assay. The anti-angiogenic potential was assessed by measuring the migration of human umbilical vein endothelial cells (HUVECs) using a Transwell assay and by quantifying Vascular Endothelial Growth Factor (VEGF) secretion via enzyme-linked immunosorbent assay (ELISA). In vivo, a subcutaneous xenograft model using Bel-7402 cells in BALB/c nude mice was established. Mice were randomized to receive vehicle or CAPE (10 mg/kg/day) for 4 weeks. Tumor growth was monitored, and microvessel density (MVD) in tumor tissues was quantified by Factor VIII immunohistochemistry. An acute toxicity study was conducted in healthy Kunming mice with a single high dose (5 g/kg) of CAPE.</p><p><strong>Results: </strong>CAPE exhibited significant anti-proliferative effects on Bel-7402 cells (IC50 = 17.6 μM) and inhibited HUVECs in a dose-dependent manner. In the xenograft model, CAPE suppressed tumor growth. CAPE demonstrated no acute toxicity in mice, suggesting preliminary safety for further investigation. Furthermore, it inhibited angiogenesis in vivo, impeded MVD in HCC specimens, and decreased VEGF secretion.</p><p><strong>Discussion: </strong>This preclinical study provides evidence that CAPE exerts antitumor effects against HCC by inhibiting cell proliferation and suppressing angiogenesis.</p><p><strong>Conclusion: </strong>These findings, coupled with a good preliminary safety profile, support CAPE as a promising candidate for further mechanistic investigation and development in HCC therapy.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832782","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":"The Emerging Role of Histone Methyltransferase ASH1L in Tumor Development.","authors":"Xiang-Yu Zhang, Yue Li","doi":"10.2174/0118715206410039251203071353","DOIUrl":"https://doi.org/10.2174/0118715206410039251203071353","url":null,"abstract":"<p><p>Histone modifications play a fundamental role in epigenetic regulation. Histone methylation mediated by enzymes like absent, small, or homeotic discs 1-like (ASH1L) has emerged as a critical process in normal cellular function and disease, particularly cancer. ASH1L, a member of the Trithorax-group (TrxG) protein family, acts as a histone methyltransferase with the ability to establish H3K36 dimethylation (H3K36me2). In recent years, an increasing number of studies have focused on the dysregulation of ASH1L in various tumors and its potential as a therapeutic target. A detailed literature survey was conducted to compile data from PubMed, SciFinder, and ScienceDirect. After screening, data extraction, and descriptive analysis, a series of related articles was retained. This comprehensive review systematically dissects the molecular mechanisms by which ASH1L modulates oncogenic processes in these cancers, emphasizing its roles in transcriptional activation of driver genes, epigenetic reprogramming, cell cycle progression, and maintenance of cancer stem cell properties. Additionally, we summarize current progress in targeting ASH1L for cancer therapy, highlighting challenges and future directions. ASH1L, as a histone methyltransferase, is associated with the tumor microenvironment, and its anti-tumor targeted therapies require further exploration in the future.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832800","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":"Chitosan-Graphene Composite for Drug Delivery in Cancer Therapy: Recent Progress and Advances.","authors":"Negar Lari Lavasani, Mohammad Hossein Roozbahani, Seyed Morteza Naghib","doi":"10.2174/0118715206393479251124110518","DOIUrl":"https://doi.org/10.2174/0118715206393479251124110518","url":null,"abstract":"<p><p>This review focuses on anticancer drug delivery systems using graphene/chitosan (CS) nanocomposites, and the present discussion explores the potential of chitosan/graphene oxide composites and their applications in wound dressings and drug delivery systems, particularly in cancer therapy. Graphene/chitosan-based drug delivery is gaining popularity due to its unique physical, chemical, and electrical properties, improving drug efficacy. The inherent biodegradability, non-toxicity, and antibacterial properties of chitosan make it a highly promising biopolymer for therapeutic interventions. Researchers have also identified graphene oxide as a non-toxic, cost-effective, and biocompatible material suitable for a diverse range of applications. Therefore, here we will examine the reasons for their use in drug delivery, especially in cancer. In addition, we will also study the combination of these two excellent materials. The combination of chitosan (CS) and graphene is currently under investigation for its enhanced therapeutic benefits.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832749","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":"Fungal β-D-Glucans: Versatile Agents in Immune Modulation, Tumor Suppression, and Nanomedicine Advances.","authors":"Ao Jin, Yicheng Peng, Dianqi Zhang, XinYi Zhou, Yaoxiang Sun, Xiang Chen","doi":"10.2174/0118715206435063260413064006","DOIUrl":"https://doi.org/10.2174/0118715206435063260413064006","url":null,"abstract":"<p><strong>Introduction/objective: </strong>β-D-Glucans, natural polysaccharides abundant in fungal cell walls, have emerged as promising immunomodulatory and antitumor biomaterials due to their unique triple-helix structure and excellent biocompatibility. Their structural versatility-defined by β-1,3/1,6-glycosidic linkages, branching patterns, and conformational transitions-enables precise optimization for targeted cancer therapy, overcoming the limitations of conventional chemotherapeutics. This article provides a comprehensive review of the structural characteristics, preparation methodologies, pharmacological functions, and underlying mechanisms of fungal β-D-glucans.</p><p><strong>Methods: </strong>A systematic review of peer-reviewed literature was conducted to delineate the structure-activity relationships of fungal β-D-glucans, with a focus on extraction methodologies, antitumor mechanisms, and nanodrug delivery applications.</p><p><strong>Results: </strong>β-D-glucans exhibit dual antitumor efficacy: (1) Direct tumoricidal effects via induction of G1/S-phase cell cycle arrest, suppression of metastasis, and oxidative stress-mediated apoptosis; (2) Immunomodulatory effects by reprogramming Tumor-Associated Macrophages (TAMs) and exerting synergistic effects with Immune Checkpoint Inhibitors (ICIs). Nano-formulations based on β-D-glucans improve targeted delivery efficiency and overcome bioavailability barriers, achieving a 3-fold higher tumor accumulation than free drugs in murine models.</p><p><strong>Discussion: </strong>Fungal β-D-glucans represent a promising therapeutic platform that integrates direct tumor cytotoxicity and immune activation for next-generation cancer treatment. Although the safety and regulatory framework for glucan-based nanomedicines is still evolving, it is imperative to prioritize the clinical development of nanoparticle- based glucan delivery systems and explore optimized synergistic combination strategies to address the key challenges of tumor heterogeneity and drug resistance.</p><p><strong>Conclusion: </strong>The unique triple-helix structure renders them excellent nanocarriers to enhance targeted drug delivery and combination therapeutic efficacy. The current clinical translation of fungal β-D-glucans is limited by the lack of standardized extraction protocols, structural variation across different fungal sources, and insufficient safety evaluation. Future research should focus on optimizing the oral delivery system of β-D-glucans and developing novel combination strategies to overcome drug resistance and accelerate their clinical translation.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721637","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}