Anti-cancer Agents In Medicinal Chemistry[JOURNAL]
Sun
200 papers
Overview of Spirooxindoline Scaffolds in Cancer Therapy.
Sharma K
Anticancer Agents Med Chem · 2026 May · PMID 42099173 · Publisher ↗
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 as...
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.
CAF Heterogeneity in Ovarian Cancer: Implications for Chemoresistance and Treatment Strategies.
Gopinath S, Balakrishnan P, Muli Y … +4 more , Ramasamy J, Puniyakotti S, Varadarajan N, Velmurugan R
Anticancer Agents Med Chem · 2026 May · PMID 42099172 · Publisher ↗
INTRODUCTION: 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...
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: 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.
Nucleobase Ionic Liquids (NBILs) Induced Apoptosis via Caspase 3 Activation and in silico Regulation of the IRE1a Pathway in Pancreatic Cancer PANC-1 Cells.
Patil P, Bansode P, Telang G … +7 more , Mishra S, Kurhe D, Mali D, Jadhav N, Dagade D, Pore D, Rashinkar G
Anticancer Agents Med Chem · 2026 May · PMID 42099171 · Publisher ↗
INTRODUCTION: 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 age...
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: 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.
Caffeic Acid Phenethyl Ester (CAPE) Inhibits Hepatocellular Carcinoma Growth and Angiogenesis via Vascular Endothelial Growth Factor Suppression: A Preclinical Evidence.
Gong L, Wang W, Deng Z … +2 more , Luo N, Peng J
Anticancer Agents Med Chem · 2026 Apr · PMID 42083950 · Publisher ↗
INTRODUCTION: 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. Thi...
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: This preclinical study provides evidence that CAPE exerts antitumor effects against HCC by inhibiting cell proliferation and suppressing angiogenesis. CONCLUSION: These findings, coupled with a good preliminary safety profile, support CAPE as a promising candidate for further mechanistic investigation and development in HCC therapy.
Preclinical Evaluation of the Methyl (Z)-2-(isothioureidomethyl)-2-pentenoate Hydrobromide: Antitumor Efficacy and Safety Profile in a Murine Melanoma Model.
Assunção LS, Kretzer IF, Rosa AG … +6 more , Vernaschi MM, Miyake JA, Nazari EM, Ferreira M, Sá MM, Creczynski-Pasa TB
Anticancer Agents Med Chem · 2026 Apr · PMID 42083949 · Publisher ↗
INTRODUCTION: 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 hav...
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: 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 therapeutic potential and translational applicability of ISMF08.
Anticancer Potential of Eudesmanolides Derived from Sphagneticola trilobata against Colorectal Cancer, by Targeting β-catenin Signalling.
Johny R, Athikkavil FM, Aiswarya SU … +7 more , Nisthul AA, Sudhesh M, Abhijith B, Krishnakumar KA, Anto RJ, Lankalapalli RS, Bava SV
Anticancer Agents Med Chem · 2026 Apr · PMID 42083948 · Publisher ↗
INTRODUCTION: 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 axi...
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: 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.
The Emerging Role of Histone Methyltransferase ASH1L in Tumor Development.
Zhang XY, Li Y
Anticancer Agents Med Chem · 2026 Apr · PMID 42083345 · Publisher ↗
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 fu...
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.
Chitosan-Graphene Composite for Drug Delivery in Cancer Therapy: Recent Progress and Advances.
Lavasani NL, Roozbahani MH, Naghib SM
Anticancer Agents Med Chem · 2026 Apr · PMID 42083344 · Publisher ↗
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...
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.
Deciphering the Molecular Interactions of Tuberculosis and Colorectal Cancer: A Network and RNA-Seq Data Analysis Approach.
Yu R, Hasan A, Ibrahim M … +2 more , Alonazi WB, Li B
Anticancer Agents Med Chem · 2026 Apr · PMID 42002962 · Publisher ↗
INTRODUCTION: A recent study revealed a correlation between TB and cancer, with individuals with a history of TB or current symptoms having a greater likelihood of developing colorectal cancer. This study aimed to explor...
INTRODUCTION: A recent study revealed a correlation between TB and cancer, with individuals with a history of TB or current symptoms having a greater likelihood of developing colorectal cancer. This study aimed to explore transcriptomics data to identify new potential common therapeutic targets for CRC and tuberculosis. METHODS: The GSE11199 dataset associated with TB and the GSE33113 dataset associated with CRC were retrieved from the Gene Expression Omnibus. The study identified commonly upregulated genes via R language, built a protein‒protein interaction network, and visualized it via Cytoscape, Cytohubba, and MCODE, revealing the role of miRNAs and TFs in regulating hub genes. RESULTS: A total of 40 genes were found to be commonly upregulated, six of which were identified as hub genes, i.e., CXCL5, MMP3, MMP1, CXCL8, CXCL11, and SPP1. In addition, 58 miRNAs and 28 TFs were found to be associated with the hub genes. DISCUSSION: Our findings revealed that key genes associated with the tumor immune microenvironment such as CXCL5, an inflammatory chemokine; CXCL8, a neutrophil-attracting chemokine; CXCL11, which is chemotactic for activated T-cells; and SPP1, which promotes the recruitment of immune cells to the tumor microenvironment and is significantly linked with various miRNAs and transcription factors, could regulate the functions of these hub genes and contribute to the progression and pathology of CRC and TB. CONCLUSION: The identified genes hold strong potential to apprise the development of targeted therapeutic strategies and advance clinical applications for patients affected by both conditions.
Hyperthermia of MCF-7 under Near Infrared Radiation in the Presence of PEGylated Graphene Oxide Nanoparticles.
Dolgikh MD, Bochkova MS, Timganova VP … +4 more , Usanina DI, Lazarev SS, Rayev MB, Zamorina SA
Anticancer Agents Med Chem · 2026 Apr · PMID 42002961 · Publisher ↗
INTRODUCTION: Breast cancer remains a major healthcare challenge due to its high incidence worldwide. Current treatment methods involve invasive surgical procedures, underscoring the urgent need for more effective and le...
INTRODUCTION: Breast cancer remains a major healthcare challenge due to its high incidence worldwide. Current treatment methods involve invasive surgical procedures, underscoring the urgent need for more effective and less invasive therapies. One promising approach explored in this study is hyperthermia-based treatment of cancer cells using NIR radiation in the presence of PEGylated graphene oxide. This method aims to leverage the photothermal properties of nanoparticles to selectively ablate cancer cells, offering a potential alternative to other therapeutic strategies. METHODS: We investigated graphene oxide coated with linear (LP-GO) or branched (BP-GO) polyethylene glycol at concentrations of 5, 25, and 50 μg/mL in combination with NIR radiation. The irradiation was performed twice for 20 minutes. Cell viability, apoptosis, and the number of MCF-7 cells were assessed at 24 and 48 hours post-irradiation using flow cytometry. RESULTS: The research shows that only LP-GO increases the temperature in a dose-dependent manner. The maximum temperature (45.9°C) was recorded at a concentration of 50 μg/mL after the second irradiation. Additionally, LP-GO is sorbed by MCF-7 cells in a dose-dependent manner. Furthermore, when LP-GO was used at concentrations of 25 and 50 μg/mL in combination with NIR irradiation, the maximum antitumor effect was observed after 48 hours, with a general apoptosis rate of 30%. DISCUSSION: We observed that after NIR irradiation of MCF-7 cells, early apoptosis was induced. According to the literature, this effect may be associated with increased levels of pro-apoptotic proteins and pro-inflammatory cytokines. In addition, apoptosis is known to be triggered after photothermal/photodynamic therapy by increasing the amount of ROS, caspase 8/9 activation, as well as caspase 3/7 and cytochrome c protein. At the same time, we did not observe a great increase in apoptosis, which may be due to the fact that hyperthermia is able to increase the expression of heat shock genes, in particular HSP70, HSP90, and HSP27, HSPВ1, which protect the cell from the negative influence of IR rays. CONCLUSION: This study demonstrates that LP-GO effectively induces hyperthermia in MCF-7 cells in a concentration- dependent manner, resulting in an increased percentage of apoptotic cells. Therefore, the combination of LP-GO with NIR irradiation shows promise as a hyperthermia-based therapeutic approach for breast cancer treatment.
Qualitative Analysis and Cytotoxic Activity of Ethanolic Extract of Piper betle Linn. Leaves: Induction of Apoptosis, Cell Cycle Arrest, and Caspase-3/7 Activation in HER2+ AU565 Breast Cancer Cell Line.
Fayyaz S, Tul-Wahab A, Irshad R … +4 more , Mir M, Zafar N, Zafar H, Choudhary MI
Anticancer Agents Med Chem · 2026 Apr · PMID 42002960 · Publisher ↗
INTRODUCTION: Piper betle, or betel vine, is a common chewing plant used for recreational purposes. Recently, there has been an increased interest in the cancer chemotherapeutic potential of dietary plants due to their a...
INTRODUCTION: Piper betle, or betel vine, is a common chewing plant used for recreational purposes. Recently, there has been an increased interest in the cancer chemotherapeutic potential of dietary plants due to their antioxidant, antiinflammatory, and anti-mutagenic actions. While previous studies have demonstrated that P. betle leave extract inhibits the proliferation of breast cancer cells in vitro, the underlying mechanisms of its anti-cancer activity remain poorly understood. In this study, we investigated the effect of P. betle leaf extract on breast cancer cell lines and identified the possible mechanisms involved. METHODS: Cell viability was assessed using the MTT assay. Annexin V and caspase-3/7 assays were used to determine apoptosis (programmed cell death). Major bioactive constituents in the extract were identified by using LC-MS and GC-MS techniques. RESULTS: We found that P. betle leaves' extract inhibited the proliferation of all the breast cancer cell lines. Mechanistic analyses revealed that P. betle mediated inhibition of cell growth is a result of cell cycle arrest and DNA fragmentation. Moreover, the expression of apoptotic genes increased, ultimately leading to the activation of caspase-3/7 and cell death. The major compounds identified were hydroxychavicol, methyl palmitate, (E)- methyl octadec-9-enoate, and coniferaldehyde. We therefore speculate that the anti-cancer effect of P. betle is largely dependent on these phytochemicals. DISCUSSIONS: In line with previously reported studies, our results demonstrate, for the first time, the anti-cancer effect of P. betle extract on the AU565 a HER2+ breast cancer cell line. Together with in silico and mechanistic approaches, we established that major compounds identified in the P. betle extract could be further evaluated as potential lead molecules against breast cancer. CONCLUSION: In summary, we report here for the first time that P. betle extract inhibits the proliferation of the AU565 (HER2+) breast cancer cell line, which may aid in advancing treatment options, particularly for HER2+ breast cancer.</p>.
Fungal β-D-Glucans: Versatile Agents in Immune Modulation, Tumor Suppression, and Nanomedicine Advances.
Jin A, Peng Y, Zhang D … +3 more , Zhou X, Sun Y, Chen X
Anticancer Agents Med Chem · 2026 Apr · PMID 42002959 · Publisher ↗
INTRODUCTION/OBJECTIVE: 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 b...
INTRODUCTION/OBJECTIVE: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSION: 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.
Targeting the Arachidonic Acid Cascade in Cancer: Recent Advances in Enzyme Inhibitor Design.
Vujić Z, Savić J, Čudina O … +2 more , Brborić J, Dobričić V
Anticancer Agents Med Chem · 2026 Apr · PMID 41968793 · Publisher ↗
INTRODUCTION: Cancer is a multifactorial disease involving multiple interrelated molecular targets and signaling pathways. Some epidemiological studies have suggested that nonsteroidal anti-inflammatory drugs could reduc...
INTRODUCTION: Cancer is a multifactorial disease involving multiple interrelated molecular targets and signaling pathways. Some epidemiological studies have suggested that nonsteroidal anti-inflammatory drugs could reduce the incidence of certain types of cancer, indicating the interplay between inflammation and cancer. Designing compounds that inhibit an enzyme of the arachidonic acid inflammatory cascade while exhibiting anticancer effects has emerged as a promising strategy. METHODS: A descriptive review and analysis of recently published studies on the synthesis of compounds that target two enzymes of the arachidonic acid cascade and simultaneously exhibit anticancer activity was performed. RESULTS: Numerous cyclooxygenase-2 (COX-2) inhibitors with anticancer activity are known. Fewer examples exist for 5-lipoxygenase (5-LOX) inhibitors, while many dual COX-2/5-LOX inhibitors also display anticancer effects. Some examples of dual inhibitors with anticancer potential include 5-LOX/microsomal prostaglandin E2 synthase (mPGES), and COX-2/soluble epoxide hydrolase inhibitors. There are also compounds designed to inhibit three targets: COX-2, 15-LOX, and carbonic anhydrase. DISCUSSION: Given the complex interplay between inflammation and cancer, the term "anticancer effects" encompasses various therapeutic opportunities, ranging from adjuvant therapy and chemoprevention to angiogenic and cytotoxic activity. CONCLUSION: This multitarget approach highlights the broad therapeutic possibilities of targeting inflammatory pathways, establishing a direction for the development of innovative anticancer therapies with improved safety profiles.
In-Silico Identification of Natural Compounds as Dual Inhibitors of Aromatase and CDK4/6: A Multi-Target Approach for ER-Positive Breast Cancer Treatment.
Yadav P, Raj VS, Yadav MK
Anticancer Agents Med Chem · 2026 Apr · PMID 41968792 · Publisher ↗
INTRODUCTION: The diagnosis of Estrogen-positive (ER+) breast cancer remains a major challenge for postmenopausal women. The progression of this disease depends heavily on estrogen signaling, which serves as an essential...
INTRODUCTION: The diagnosis of Estrogen-positive (ER+) breast cancer remains a major challenge for postmenopausal women. The progression of this disease depends heavily on estrogen signaling, which serves as an essential target for treatment strategies. The progression of the disease and the development of resistance to treatment occur because of abnormalities in the cyclin D1-CDK4/6-Rb pathway, even though aromatase inhibitors are effective. METHODS: To identify potential dual inhibitors of aromatase and CDK4/6, 170,269 natural compounds from the Asinex database were screened using multi-target virtual screening. The top hits underwent molecular docking, ADMET profiling, density functional theory (DFT) analysis, 100 ns Molecular Dynamics (MD) simulations, and MM-GBSA binding energy calculations as part of a comprehensive in silico analysis. RESULTS: In the initial phase, 76 aromatase-targeting compounds were screened against CDK4 and CDK6. Two dual-target candidates demonstrated promising potential: LAS52119664 and BBF30702300, which showed aromatase (-8.21 kcal/mol) and CDK4 (-197.87 ± 14.09 kcal/mol) binding, and BBF30702300, which showed aromatase (-6.21 kcal/mol) and CDK6 (-110.58 ± 8.43 kcal/mol) binding. DISCUSSION: The DFT analysis demonstrated that the HOMO-LUMO gaps were 0.184 and 0.181 eV, which indicated high reactivity. Both complexes maintained stability during a 100-nanosecond molecular dynamics simulation, as shown by their steady RMSD and RMSF values. ADMET profiling and in silico toxicity predictions confirmed the drug-like features of these compounds. ER+ breast cancer therapy may benefit from these compounds, which act as dual inhibitors. CONCLUSION: Both LAS52119664 and BBF30702300 emerged as novel and promising natural dual inhibitors of aromatase and CDK4/6, providing a basis for future experimental validation and the development of multitargeted therapies for ER-positive breast cancer.
Recent Advances in Natural Phytocompounds for the Chemotherapeutic Management of Head and Neck Squamous Cell Carcinoma from 2018-2024.
Nooreen Z, Rai V, Sachan H … +2 more , Rai AK, Tandon S
Anticancer Agents Med Chem · 2026 Apr · PMID 41968791 · Publisher ↗
The most prevalent cancers of the head and neck are oral squamous cell carcinomas, which arise from the mucosal epithelium of the oral cavity, throat, and larynx. According to GLOBOCAN, oral squamous cell carcinoma is th...
The most prevalent cancers of the head and neck are oral squamous cell carcinomas, which arise from the mucosal epithelium of the oral cavity, throat, and larynx. According to GLOBOCAN, oral squamous cell carcinoma is the sixth most frequent malignancy worldwide and is expected to increase in prevalence by 30% by 2030. A thorough understanding of the underlying molecular processes can lead to novel therapeutic approaches that utilize phytochemicals, either alone or in combination with currently approved medicines, for a range of malignancies. Phytochemicals present in food can influence the antioxidant status of the oral cavity and contribute to its protection. Plant-derived antioxidants, including polyphenols, have been shown to scavenge reactive nitrogen species, chelate ions, and mitigate adverse effects. The mucosal and submucosal compartments are involved in enhanced immune responses, decreased cell proliferation, increased cell death, and diminished regenerative capacity. To effectively prevent and treat oral squamous cell carcinoma, this review summarizes some of the most potent phytochemicals. These compounds can arrest the cell cycle, induce differentiation and apoptosis, inhibit angiogenesis, and suppress the invasive and metastatic properties of cancer cells. Their mechanisms of action include cytochrome-c release, loss of mitochondrial membrane potential, downregulation of antiapoptotic proteins, upregulation of pro-apoptotic proteins, activation of caspases and p53, inhibition of the Akt/mTOR signaling pathway, and modulation of NF-κB, STAT3, and PI3K phosphorylation. Additionally, phytochemicals can reduce the damage caused by radiation and chemotherapy to healthy cells during treatment. This review highlights plant extracts and their bioactive compounds reported for the management of head and neck cancers from 2018 to 2024.
Poly(2-oxazolines) as Precision Nanocarriers in Triple-Negative Breast Cancer: Advancing Targeted Chemotherapy Through Polymeric Innovation.
Chauhan SB, Jain C, Yadav A … +1 more , Singh I
Anticancer Agents Med Chem · 2026 Apr · PMID 41968790 · Publisher ↗
INTRODUCTION: Poly(2-ethyl-2-oxazoline) (POx) has emerged as a highly promising drug delivery polymer due to its biocompatibility, stealth-like behavior, and versatile functionalization options. POx-based nanocarriers of...
INTRODUCTION: Poly(2-ethyl-2-oxazoline) (POx) has emerged as a highly promising drug delivery polymer due to its biocompatibility, stealth-like behavior, and versatile functionalization options. POx-based nanocarriers offer significant advantages for targeted drug delivery in oncology, particularly for challenging tumors such as triple-negative breast cancer (TNBC). METHODS: Recent literature from 2015 to 2025 on the synthesis, characterization, and biological applications of POx-based nanocarriers was systematically reviewed. Emphasis was placed on drug conjugation techniques, in vitro and in vivo performance, and computational studies that inform design optimization. RESULTS: POx micelles and hybrid systems demonstrate improved encapsulation efficiency, reduced off-target toxicity, and sustained drug release, achieving effective tumor targeting via the enhanced permeability and retention (EPR) effect. Notably, POx micelles loaded with β-elemene exhibit dual pH/GSH-responsive behavior with >92% encapsulation efficiency. Computational modeling has guided micelle design and predicted critical drug-polymer interactions. DISCUSSION: The structural flexibility of POx enables the engineering of dual-drug carriers and theranostic platforms. Clinical translation is progressing, although challenges remain regarding large-scale synthesis and regulatory standardization. Integration of POx-based systems into combination therapies and personalized oncology strategies represents a promising path forward, supported by encouraging preclinical results. CONCLUSION: POx nanocarriers exhibit strong translational potential for TNBC due to high drug loading, biocompatibility, and tunable release profiles. They provide enhanced tumor accumulation, active targeting, and the ability to overcome multidrug resistance, supported by favorable pharmacokinetics and computational design insights. Remaining challenges include large-scale production, long-term safety assessment, and regulatory approval. Future directions focus on dual- and stimuli-responsive systems and their integration into precision oncology to accelerate clinical translation.
Pomegranate Oil Nanoemulsion as a Nanotherapeutic Strategy Against Breast and Colon Cancer: Induction of Apoptosis and Inhibition of Cell Migration.
Aljadani M, Binothman N, Alshehri S … +1 more , Altarjami LR
Anticancer Agents Med Chem · 2026 Apr · PMID 41944113 · Publisher ↗
INTRODUCTION: Cancer is increasingly recognized as a chronic condition. However, current anticancer therapies have several limitations that considerably impact patient quality of life. Therefore, we aimed to develop and...
INTRODUCTION: Cancer is increasingly recognized as a chronic condition. However, current anticancer therapies have several limitations that considerably impact patient quality of life. Therefore, we aimed to develop and characterize a pomegranate (Punica granatum) oil-based nanoemulsion (PG-NE) with enhanced anticancer properties. We further aimed to evaluate its cytotoxic, pro-apoptotic, and anti-migratory effects on human breast (MCF-7) and colon (HCT-116) cancer cell lines. METHODS: PG-NE was formulated via high-energy emulsification and characterized by dynamic light scattering to determine droplet size, polydispersity index (PDI), and zeta potential. Its cytotoxicity was measured by the MTT assay, whereas apoptosis and migration were assessed by Annexin V/PI flow cytometry and scratchwound- healing assays, respectively. RESULTS: PG-NE exhibited a mean droplet size, PDI, and zeta potential of 283.67 ± 1.15 nm, 0.17 ± 0.01, and - 35.17 ± 0.06 mV, respectively, indicating uniform nanoscale distribution and good colloidal stability. Compared with mitomycin C (MMC), PG-NE significantly decreased cancer cell viability, enhanced apoptotic induction, and strongly inhibited migration in both MCF-7 and HCT-116 cells. DISCUSSION: The findings indicate that nanoencapsulation enhances the anticancer efficacy of pomegranate oil by increasing its solubility and bioavailability, thereby supporting its potential as a plant-derived nanotherapeutic in integrative oncology. CONCLUSION: PG-NE exhibited potent cytotoxic, pro-apoptotic, and antimigratory activities in vitro. Its physicochemical stability and biological activity support its potential use as a chemopreventive or adjunctive agent.
Decoding the Anticancer Potential of Natural N-Heterocycles: Molecular Frameworks, Bioactivity, and Mechanistic Advances.
Saini H, Mehra A, Mittal A
Anticancer Agents Med Chem · 2026 Mar · PMID 41940431 · Publisher ↗
Cancer is the leading cause of death and morbidity worldwide. Numerous scientists are trying to develop new anticancer medications that are more potent and less hazardous. This review, in contrast to previous reviews, fo...
Cancer is the leading cause of death and morbidity worldwide. Numerous scientists are trying to develop new anticancer medications that are more potent and less hazardous. This review, in contrast to previous reviews, focuses on the latest research findings from 2020-2025 on N-heterocyclic moieties as natural anticancer agents. This review provides a contemporary evaluation that integrates recent mechanistic discoveries, emerging nanotechnology-based delivery approaches, and translational progress relevant to natural Nheterocyclic anticancer agents. The literature was collected from online sources such as PubMed, Science Direct, Embase, and Google Scholar by searching with keywords like research paper on Natural N-heterocyclic products having anticancer activity, etc. The findings suggest that combining naturally obtained N-heterocyclic compounds with nanotechnology can provide us with a low-toxic anticancer drug in the future. The process of combining natural products containing N-Heterocyclic moieties with nanotechnology can be a game-changer for the development of anticancer medications. Still, there is a lot of research to be done in this area, which can change the viewpoint of the world regarding the treatment of cancer.
Decoding Sarcoma Drug Resistance: From Molecular Mechanisms to Precision Interventions.
Lyu G, Li D
Anticancer Agents Med Chem · 2026 Mar · PMID 41940430 · Publisher ↗
INTRODUCTION: This study aims to systematically synthesize current knowledge on the molecular and microenvironmental mechanisms driving sarcoma drug resistance, and to evaluate emerging precision strategies for overcomin...
INTRODUCTION: This study aims to systematically synthesize current knowledge on the molecular and microenvironmental mechanisms driving sarcoma drug resistance, and to evaluate emerging precision strategies for overcoming these obstacles. METHODS: We conducted a comprehensive literature review (PubMed, Web of Science, Embase; inception- 31 July 2025) using MeSH and free-text terms relating to sarcoma, drug resistance, biomarkers, and precision medicine. Inclusion criteria were peer-reviewed original or review studies in human or pre-clinical sarcoma models reporting resistance mechanisms or counter-strategies. Data were qualitatively categorized by resistance pathways (efflux pumps, DNA repair, apoptosis inhibition, secondary mutations, and immune evasion) and linked to therapeutic countermeasures. RESULTS: ABC transporter over-expression (especially P-gp) and heightened DNA repair via homologous recombination were recurrent chemo-resistance drivers. Targeted-therapy failure was dominated by secondary KIT/PDGFRA or NTRK mutations, bypass signaling (PI3K/AKT ↔ RAS/MAPK), and epithelial- mesenchymal transition. Immune escape occurred through antigen loss, MHC-I down-regulation, adenosine- rich immunosuppressive microenvironments, and T-cell exhaustion (PD-1/CTLA-4 up-regulation). Epigenetic dysregulation (EZH2, HDAC, DNMT) further fostered stem-like survival. Liquid-biopsy ctDNA enabled real-time resistance monitoring. Next-generation TKIs, dual-pathway inhibitors, epigenetic drugs, and rationally designed chemo-immuno combinations showed synergistic activity in pre-clinical and early clinical studies. DISCUSSION: Integrating multi-omics profiling, liquid biopsies, and patient-derived organoids into adaptive trial designs can individualize therapy sequences and delay resistance. Limitations include heterogeneous sarcoma biology, limited clinical validation, and economic barriers to the implementation of precision. CONCLUSION: Resistance to drugs in sarcoma is multifactorial and changeable. Nevertheless, fusing mechanistic knowledge with biomarker - guided combination/sequential therapies offers a clear way to improve patient situations.
Glycyrrhetinic Acid in Cancer Therapy: Mechanistic Insights, Therapeutic Potential, and Future Directions.
Yoqubova N, Gulyamov S, Abdulla-Zoda D … +4 more , Tursunov K, Sharipov A, Rizaev K, Hu X
Anticancer Agents Med Chem · 2026 Mar · PMID 41940429 · Publisher ↗
Cancer presents a significant and growing global health challenge in the 21st century, marked by a rising number of new diagnoses and cancer-related deaths reported annually. Glycyrrhetinic Acid (GA), a triterpenoid comp...
Cancer presents a significant and growing global health challenge in the 21st century, marked by a rising number of new diagnoses and cancer-related deaths reported annually. Glycyrrhetinic Acid (GA), a triterpenoid compound derived from the licorice plant, Glycyrrhiza glabra, G. inflata, and G. uralensis, has a long-standing history of use in traditional healing practices. In this comprehensive review, the evolving research on GA's pharmacological properties published between 2015 and 2024, with a specific focus on its potential as a cancer therapy, is critically analyzed. In preclinical studies, GA showed anti-tumor effects and modulated several cellular pathways involved in cancer growth. Despite this promising anti-tumor activity, GA's clinical use is still being evaluated because of poor solubility and low bioavailability. A clear understanding of GA's complex pharmacokinetics is necessary to optimize its clinical application. This work explores how GA may act against cancer, including its capacity to enhance chemotherapeutic treatments and its interactions in the tumor microenvironment. In addition, this paper critically reviews GA's therapeutic potential across different cancer types and discusses new formulation approaches, pointing to key directions for future clinical and translational studies. This review summarizes the existing evidence on GA and discusses its potential use as a treatment in oncology. Further research is needed to assess GA's effectiveness and safety in clinical studies. Such investigations can help translate laboratory results into practical use in clinical settings.
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