Anti-cancer Agents In Medicinal Chemistry[JOURNAL]
Sun
200 papers
Targeting Telomere Shelterin Protein TPP1 with Elbasvir: Induction of Autophagy and Suppression of Esophageal Cancer Tumorigenesis.
Tang M, Yang M, Wen J … +5 more , Liu X, Xu L, Ma Q, Zhong X, Guo X
Anticancer Agents Med Chem · 2025 Oct · PMID 41088905 · Publisher ↗
INTRODUCTION: Esophageal cancer often develops insidiously, with most cases diagnosed at an advanced stage. Currently, the pathogenesis of esophageal cancer remains unclear, treatment outcomes are poor, and the five-year...
INTRODUCTION: Esophageal cancer often develops insidiously, with most cases diagnosed at an advanced stage. Currently, the pathogenesis of esophageal cancer remains unclear, treatment outcomes are poor, and the five-year survival rate is low. To tackle the significant clinical challenges of difficult diagnosis and unfavorable prognosis, it is crucial to actively investigate the disease's pathogenesis. This study explored the involvement of telomere shelterin protein TPP1 in the pathogenesis of esophageal cancer and identified potential therapeutic agents for its treatment. METHODS: The expression level of TPP1 protein in 54 pairs of esophageal cancer tissues and paired adjacent tissues was detected via immunohistochemistry. The impact of TPP1 silencing and Elbasvir administration on the growth of KYSE150 and TE1 esophageal cancer cell lines was assessed utilizing Cell Counting Kit-8 and colony formation assays. Cell migration was assessed through Transwell and scratch assays. Fluorescence microscopy was employed to observe autophagosome formation, while flow cytometry measured the fluorescence intensity of autophagy markers LC3 and P62 in TPP1-silenced KYSE150 and TE1 cells. Western blotting was utilized to examine the alterations in TPP1, the AKT-mTOR signaling pathway, autophagy-related proteins, and other associated proteins. RESULTS: TPP1 levels were notably elevated in esophageal squamous cell carcinoma tissues relative to adjacent normal tissues. Suppression of TPP1 substantially reduced the growth and movement of esophageal cancer cells in vitro, while triggering autophagy via the AKT-mTOR signaling pathway, highlighting TPP1's cancerpromoting function in esophageal cancer. DISCUSSION: Elbasvir effectively suppressed the growth and spread of KYSE150 and TE1 cell lines in vitro, downregulating TPP1 protein expression in relation to time and dosage. Additional investigations revealed that Elbasvir also inhibited the AKT-mTOR signaling axis and induced autophagy by targeting TPP1. Notably, rescue experiments demonstrated that 3-MA could reverse the inhibitory effects on proliferation, migration, and autophagy induced by TPP1 silencing or Elbasvir treatment in KYSE150 and TE1 cells. CONCLUSION: TPP1 emerges as a compelling diagnostic indicator and a potential treatment focus in esophageal cancer, with Elbasvir offering promise as a novel therapeutic agent.
GPR65 as a Laryngeal Cancer Risk Gene Identified through Single-Cell Transcriptomics, Mendelian Randomization Analysis, and Experimental Validation.
Mao QJ, Zhou YQ, Zhao BS … +4 more , Wu H, Wang SZ, Zhang ZX, Ni HS
Anticancer Agents Med Chem · 2026 · PMID 41088904 · Publisher ↗
INTRODUCTION: Laryngeal cancer is a common malignant tumor of the head and neck worldwide. This study aimed to identify potential risk genes, with a particular focus on GPR65, and to investigate its functional mechanism...
INTRODUCTION: Laryngeal cancer is a common malignant tumor of the head and neck worldwide. This study aimed to identify potential risk genes, with a particular focus on GPR65, and to investigate its functional mechanism in pathogenesis of laryngeal cancer. MATERIALS AND METHODS: Comprehensive analyses, including scRNA-seq analysis, genome-wide association study (GWAS), eQTL, and TCGA data, were conducted to identify risk genes for laryngeal cancer and characterize the function of these risk genes. Next, qRT-PCR, immunohistochemistry, cell proliferation, cell migration, and invasion assays were employed to verify the expression of GPR65 and its function in laryngeal squamous cell carcinoma (LSCC) . RESULTS: Single-cell analysis screened 416 highly expressed genes in CD8+ central memory T cells (CD8_CM). Mendelian randomization (MR) analysis identified GPR65 as a crucial gene in the development of laryngeal cancer. GPR65 expression was significantly elevated in the tumor tissues compared to normal tissues, with particularly high levels observed in stage IV HNSCC. , LSCC cell lines (TU686 and Hep-2) exhibited marked upregulation of GPR65 relative to normal epithelial cells, and siRNA-mediated silencing of GPR65 suppressed the proliferation, migration, and invasion of LSCC cells. Furthermore, GPR65 expression showed a positive correlation with immune cell infiltration, particularly CD8+ T cells and M1 macrophages. DISCUSSION: This study identified GPR65 as a potential risk gene for laryngeal cancer through single-cell transcriptomics and MR analyses and provided novel evidence of its involvement in the development of the cancer. CONCLUSION: The present findings showed that highly expressed GPR65 was a tumor-promoting gene in laryngeal cancer, showing its clinical value as a potential therapeutic target.
Novel PD-L1 Small-Molecule Inhibitors Advancing Cancer Immunotherapy.
Awadasseid A, Wu M, Zhang F … +3 more , Song Y, Wu Y, Zhang W
Anticancer Agents Med Chem · 2025 Oct · PMID 41051039 · Publisher ↗
INTRODUCTION: The emergence of immune checkpoint inhibitors has revolutionized the treatment of cancer. Among these, the programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis remains a critical ta...
INTRODUCTION: The emergence of immune checkpoint inhibitors has revolutionized the treatment of cancer. Among these, the programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis remains a critical target. However, resistance to current biologics necessitates the development of novel Small- Molecule Inhibitors (SMIs) with distinct mechanisms and improved pharmacological profiles. This review provides a comprehensive analysis of recent progress in PD-L1-targeting SMIs, including original compounds from our laboratory. METHODS: We conducted a structured literature review using electronic databases such as PubMed, Scopus, and Web of Science. Articles published between 2015 and 2025 were included based on relevance to small-molecule PD-L1 inhibitors in cancer immunotherapy. Key data were extracted and synthesized regarding molecular design strategies, mechanisms of action, pharmacokinetics, and therapeutic efficacy. Compounds synthesized in our laboratory (Compounds 5-10 [A56]) were evaluated using in vitro assays, including PD-L1/PD-1 binding inhibition, cancer cell viability assays, and gene expression profiling. RESULTS: Recent SMIs exhibit diverse functional profiles: direct blockade of PD-1/PD-L1 interaction, intracellular PD-L1 modulation, and transcriptional downregulation. Notably, Compound 7 demonstrated significant suppression of PD-L1 mRNA expression, while Compounds 9 and 10 (A56) achieved nanomolar-level binding affinity. These findings reflect innovative approaches to overcoming immune resistance and enhancing antitumor responses. DISCUSSIONS: Our findings underscore a trend toward multifunctional PD-L1-targeting SMIs that operate through both extracellular and intracellular mechanisms. Compounds from our laboratory represent potential leads for further optimization and clinical translation. However, challenges remain regarding oral bioavailability, metabolic stability, and immune-related adverse events. CONCLUSION: Small-molecule PD-L1 inhibitors offer a promising avenue for expanding cancer immunotherapy. Our review highlights key advances and introduces novel small-molecule PD-L1 inhibitors with strong potential for future development, particularly in combination regimens.
Targeting TGF-βR1 Signaling Pathway in Pancreatic Cancer: A Potential Approach with Synthetic Flavanols.
Cordeiro R, Bhitre M, Varma S … +2 more , Waragade S, Varma S
Anticancer Agents Med Chem · 2025 Oct · PMID 41047671 · Publisher ↗
INTRODUCTION: Pancreatic adenocarcinoma is a highly aggressive cancer with a poor prognosis and a five-year survival rate of just 13%. Its asymptomatic onset, rapid progression, and resistance to therapy make it challeng...
INTRODUCTION: Pancreatic adenocarcinoma is a highly aggressive cancer with a poor prognosis and a five-year survival rate of just 13%. Its asymptomatic onset, rapid progression, and resistance to therapy make it challenging to treat. Transforming Growth Factor-β (TGF-β) signaling, particularly through TGF-β Receptor 1 (TGF-βR1/ALK-5), plays a major role in tumor progression by inducing Epithelial-Mesenchymal Transition (EMT), immune evasion, and apoptosis resistance. Targeting ALK-5 is a promising strategy for therapeutic intervention. METHODS: Twenty-nine synthetic flavonols were designed to inhibit ALK-5 and docked using Schrodinger's Glide XP. The compounds were synthesized via a green, one-pot method and characterized using 1H-NMR, 13CNMR, Mass Spectrometry, CHN analysis, and IR spectroscopy. The anti-cancer activity was evaluated against MiAPaCa-2 pancreatic cancer cells by measuring GI50, TGI, and LC50. ALK-5 inhibition was quantified using the ADP-Glo® Kinase Assay, assessing ATP transfer. RESULTS: RFL-1 showed the strongest binding affinity (-9.38 kcal/mol) at ALK-5's active site and the highest kinase inhibition (ATP transfer: 3.67%), outperforming quercetin (9.22%). It also demonstrated an IC50 of 14.92 ± 3.54 μM. Ten flavonols exhibited strong cytotoxicity (GI50 < 10 μM), while four others showed moderate activity (GI50 = 23-26 μM). DISCUSSION: RFL-1 and related flavonols (RFL-12, RFL-20, RFL-25, RFL-28) effectively inhibited ALK-5 and suppressed the growth of pancreatic cancer cells. Their dual activity supports further development as targeted anti-cancer agents. CONCLUSION: Synthetic flavonols, particularly RFL-1, show promise as ALK-5 inhibitors and potential therapies for pancreatic adenocarcinoma, warranting further in vivo validation.
Induction of Apoptosis and Activation of Endoplasmic Reticulum Stress by SJ6986 in Diffuse Large B-cell Lymphoma.
Zhang C, Jiang B, Liang X … +4 more , Chen Y, Li Z, Zhao M, Lin D
Anticancer Agents Med Chem · 2025 Sep · PMID 41029930 · Publisher ↗
INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is one of the most prevalent hematological malignancies with high mortality. G1 to S phase transition 1 (GSPT1), a key translation termination factor involved in protei...
INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is one of the most prevalent hematological malignancies with high mortality. G1 to S phase transition 1 (GSPT1), a key translation termination factor involved in protein synthesis, has been implicated in tumor progression. This study aimed to investigate the effectiveness and underlying mechanisms of the GSPT1 degrader SJ6986 in DLBCL. METHODS: The TCGA and GTEx datasets were utilized to assess the expression of GSPT1 in DLBCL. The viability and proliferation of DLBCL cells were detected using the Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis was detected via flow cytometry. The expression of GSPT1 was evaluated using qRT-PCR and Western blot. Xenograft mouse models were employed to explore the in vivo therapeutic potential of SJ6986. RNA sequencing was used to explore the potential mechanism of SJ6986 in DLBCL. RESULTS: This study first identified that GSPT1 is highly expressed in DLBCL and demonstrated that its genetic knockdown significantly suppressed the activity of DLBCL cells. Furthermore, it was found that SJ6986 effectively reduced the proliferation of DLBCL cells, induced cell apoptosis, and inhibited tumor growth in vivo without significant toxicity. Mechanistically, RNA sequencing analysis showed that the endoplasmic reticulum (ER) stress was significantly triggered following SJ6986 treatment, and SJ6986 was found to activate the ER stress-related apoptosis in DLBCL cells. DISCUSSION: Our findings suggested that SJ6986 exerts its anti-tumor effects in DLBCL and activates the ER stress-related apoptotic signaling. These results supported SJ6986 as a viable anticancer drug for treating DLBCL. Future studies should further investigate its mechanism and evaluate its clinical application value. CONCLUSIONS: This study validated the efficacy and safety of SJ6986 in treating DLBCL and discovered its role in inducing ER stress and subsequent apoptosis, offering a promising therapeutic option for DLBCL patients.
PRR22: A Novel Prognostic Indicator and Therapeutic Target for Prostate Cancer.
Chen W, Ding G, Zhong Y … +5 more , Lao M, Zhang Q, Li D, Deng W, Chen Y
Anticancer Agents Med Chem · 2025 Sep · PMID 41029016 · Publisher ↗
INTRODUCTION: Prostate cancer (PRAD) remains a leading malignancy with limited prognostic biomarkers and therapeutic targets. PRR22, a proline-rich protein-coding gene, has a role in PRAD that remains undefined. This stu...
INTRODUCTION: Prostate cancer (PRAD) remains a leading malignancy with limited prognostic biomarkers and therapeutic targets. PRR22, a proline-rich protein-coding gene, has a role in PRAD that remains undefined. This study is the first to systematically investigate the clinical relevance and mechanistic implications of PRR22 in PRAD. METHODS: PRR22 expression was analyzed in TCGA-PRAD (n = 501), GSE55945, and the Human Protein Atlas datasets. Prognostic value was assessed via Kaplan-Meier and multivariate Cox analyses. Mechanistic insights were derived from GSEA, immune infiltration profiling, MSI/mRNA-si correlations, and drug sensitivity analysis. Experimental validation was performed via qRT-PCR in PRAD cell lines. RESULTS: PRR22 was significantly upregulated in PRAD tissues compared to normal tissues (p < 0.001) and independently predicted shorter progression-free survival (HR = 1.82, p = 0.009). Novel associations were identified between PRR22 and TGF-β signaling, immune evasion (e.g., LAG3 upregulation), microsatellite instability (MSI), and stemness (mRNA-si). High PRR22 correlated with resistance to multiple drugs (e.g., bicalutamide, vorinostat). DISCUSSION: PRR22 overexpression in PRAD is linked to poor prognosis and immune regulation, suggesting its potential as a prognostic biomarker and therapeutic target. Future research should focus on clinical validation and on exploring the molecular mechanisms underlying PRR22's role in PRAD. CONCLUSION: PRR22 is a novel, independent prognostic biomarker and actionable therapeutic target in PRAD, linking tumor aggressiveness to immune microenvironment remodeling and drug resistance. These findings establish PRR22 as a candidate for clinical implementation in risk stratification and targeted therapy.
Apoptosis-Mediated Anticancer Activity of Zinc Oxide Nanoparticles Derived and Characterized from Halophila beccarii.
Sarilla J, Mathakala V, Palempalli UMD
Anticancer Agents Med Chem · 2025 Sep · PMID 41029015 · Publisher ↗
INTRODUCTION: Recent advancements in nanomedicine have drawn attention to the use of zinc oxide nanoparticles as apoptotic agents to address triple-negative breast cancer. Halophila beccarii-mediated zinc oxide nanoparti...
INTRODUCTION: Recent advancements in nanomedicine have drawn attention to the use of zinc oxide nanoparticles as apoptotic agents to address triple-negative breast cancer. Halophila beccarii-mediated zinc oxide nanoparticles (Hb-ZnONPs) were fabricated using zinc acetate dihydrate as the precursor. METHODS: The fabricated nanoparticles were characterized based on morphological, structural, and elemental composition using SEM and XRD. The antiproliferative potential of Hb-ZnONPs was studied using the BT-549 cell line as an in vitro model, employing the MTT assay and Annexin V-FITC/PI-based flow cytometry analysis. RESULTS: The Hb-ZnONPs exhibited characteristic absorption maxima at 367 nm with a particle size of 35 nm and -44.7 mV stability. XRD confirmed the hexagonal wurtzite structure with an elemental composition of 62.3% Zn and 25.79% Oxygen. The Hb-ZnONPs demonstrated significant cytotoxicity against BT-549 cells, with 35.26% apoptosis at 5 μg/ml and 38.25% apoptosis at 10 μg/ml. However, cells in the late apoptosis stage increased from 14.48% at 5 μg/ml to 28.16% at 10 μg/ml, indicating a nearly twofold increase with the higher concentration. CONCLUSION: Hb-ZnONPs may act as promising apoptotic inducers in the chemotherapy of breast cancer.
Rosmarinic Acid as a Potential Therapeutic Agent against Neuroblastoma: Anticancer Activity and Molecular Docking Insights.
Yumrutaş P, Taşdemir D, Yumrutaş Ö
Anticancer Agents Med Chem · 2025 Sep · PMID 40999617 · Publisher ↗
INTRODUCTION: Rosmarinic acid (RA) is a phenolic acid known for its important biological activities. Although it has been shown to inhibit various cancer cell types, its effects on the suppression and induction of apopto...
INTRODUCTION: Rosmarinic acid (RA) is a phenolic acid known for its important biological activities. Although it has been shown to inhibit various cancer cell types, its effects on the suppression and induction of apoptosis in neuroblastoma cells remain unclear. In this study, the antiproliferation and apoptosis-inducing effects of various concentrations of rosmarinic acid on neuroblastoma cells (SH-SY5Y) were investigated. Additionally, molecular docking analysis was conducted to examine the interaction between rosmarinic acid and the antiapoptotic protein BCL2. METHODS: SH-SY5Y cells were treated with rosmarinic acid at concentrations of 50, 100, 150, and 200 μg/ml for 24 hours. The percentages of apoptotic and necrotic cells in cultures treated with the lowest and highest concentrations were assessed using the Annexin V/PI staining method. Furthermore, the interaction between rosmarinic acid and BCL2 protein was analyzed using molecular docking techniques. RESULTS: The viability of rosmarinic acid-treated SH-SY5Y cells decreased. In SH-SY5Y cells, the percentage of late apoptotic cells increased to 40%. Molecular docking results showed that the benzene ring of rosmarinic acid formed pi-alkyl interactions with PHE71 and van der Waals interactions with SER64, ALA72, SER75, and VAL115 of BCL2. The lowest binding energy was calculated as -7.2 kcal/mol. DISCUSSION: RA demonstrated a suppressive effect on SH-SY5Y cells by targeting the antiapoptotic protein BCL2, suggesting a potential mechanism of action through the induction of apoptosis. CONCLUSION: RA inhibited neuroblastoma SH-SY5Y cell proliferation and induced apoptotic cell death. It inhibited the proliferation of neuroblastoma SH-SY5Y cells and promoted apoptotic cell death, potentially through interaction with the BCL2 protein.
A Review of the Anticancer Properties of Cedrol and its Molecular Mechanisms.
Pourbagher Shahri AM, Negah SS, Moghbeli M … +2 more , Saburi E, Forouzanfar F
Anticancer Agents Med Chem · 2025 Sep · PMID 40999616 · Publisher ↗
Despite decades of research on promising new therapies, cancer remains a leading cause of morbidity and mortality. Over the years, extensive research has been conducted on the potential anticancer effects of various medi...
Despite decades of research on promising new therapies, cancer remains a leading cause of morbidity and mortality. Over the years, extensive research has been conducted on the potential anticancer effects of various medicinal plants. One extremely promising agent or adjuvant that may be utilized for the prevention/ treatment of several malignancies is cedrol, a naturally occurring sesquiterpene. Cedrol modulates multiple molecular pathways involved in the protracted carcinogenesis process, including the generation of reactive oxygen species, activation of pro-death autophagy, inhibition of survival signals, promotion of apoptosis, and inhibition of minichromosome maintenance proteins. This review suggests that cedrol might be a unique medication for the treatment of glioblastoma, lung cancer, and colorectal cancers. Further in-depth investigations of cedrol's anticancer mechanisms are needed.
Targeting the Lin28/let-7 Axis with Compounds to Regulate Transcriptional Control in Cancer.
Wang X, Van PKT, Liu B … +2 more , Zhao T, Wu YS
Anticancer Agents Med Chem · 2026 · PMID 40968436 · Publisher ↗
Lin28 is a pivotal RNA-binding protein that regulates the biogenesis of let-7 microRNAs, which play a crucial role in the post-transcriptional regulation of oncogenes in cancer. The Lin28/let-7 axis is integral to the re...
Lin28 is a pivotal RNA-binding protein that regulates the biogenesis of let-7 microRNAs, which play a crucial role in the post-transcriptional regulation of oncogenes in cancer. The Lin28/let-7 axis is integral to the regulation of key cellular processes such as proliferation, differentiation, and apoptosis. Lin28 promotes the upregulation of oncogenes, including MYC, RAS, and HMGA2, by inhibiting the maturation of let-7, thereby facilitating tumor initiation, progression, and metastasis. Consequently, targeting the Lin28/let-7 interaction has emerged as a promising therapeutic strategy, particularly for malignancies that lack specific molecular targets. This approach holds potential for downregulating oncogene expression and inhibiting tumor progression. Through a comprehensive review of the literature, this article classifies Lin28/let-7 inhibitors into three categories: CSD/ZKD inhibitors, non- CSD/ZKD inhibitors, and let-7 restorers. CSD/ZKD inhibitors, such as TPEN and KCB3602, function by binding to the CSD or ZKD domains of Lin28, thereby inhibiting its activity. Non-CSD/ZKD inhibitors, including compounds like C1632 and Simvastatin, have been identified as molecules that can reduce Lin28 activity, though their binding sites remain unknown. Let-7 restorers, on the other hand, do not directly target Lin28 but instead work indirectly by modulating the activity of associated molecules, such as Zcchc11 and Zcchc6, thereby promoting the restoration of let-7 expression levels. Notable examples of these include IPA-3 and FPA124. This review summarizes recent advances in the development of Lin28/let-7 inhibitors and their therapeutic potential, providing an important reference for ongoing research on Lin28 inhibitors in cancer therapy.
Preface.
Carradori S
Anticancer Agents Med Chem · 2026 · PMID 40965019 · Publisher ↗
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State of the Art of IDH Inhibitors: Emerging Questions and Perspectives.
de Lima JAL, Lima LM
Anticancer Agents Med Chem · 2025 Sep · PMID 40965018 · Publisher ↗
Isocitrate Dehydrogenases (IDH) are ubiquitous enzymes essential for cellular metabolism, including the Krebs cycle, glutamine metabolism, lipogenesis, and redox balance. Mutations in IDH1 and IDH2 are implicated in seve...
Isocitrate Dehydrogenases (IDH) are ubiquitous enzymes essential for cellular metabolism, including the Krebs cycle, glutamine metabolism, lipogenesis, and redox balance. Mutations in IDH1 and IDH2 are implicated in several tumors - gliomas, Acute Myeloid Leukemia (AML), cholangiocarcinoma - altering enzyme activity and causing the overproduction of 2-hydroxyglutarate (2-HG). This oncometabolite disrupts α-KGdependent proteins, impairing key processes such as differentiation, division, and DNA repair. Understanding these genetic, biochemical, and clinical aspects has made IDH enzymes promising therapeutic targets, prompting the development of targeted inhibitors for tumors harboring IDH1 or IDH2 point mutations. Selective inhibitors like ivosidenib (AG-120) and enasidenib (AG-221), targeting mutant IDH1 and IDH2 respectively, block 2- HG production and induce differentiation, achieving clinical success - particularly in AML. However, resistance due to secondary mutations, especially in the allosteric binding site, remains a major obstacle. In response, novel approaches have emerged, such as covalent inhibitors like LY3410738, which irreversibly bind mutant residues, and dual inhibitors like vorasidenib (AG-881), which act on both IDH1 and IDH2 mutations and penetrate the blood-brain barrier for treating solid tumors. Still, many clinical factors must be considered. This review explores the current landscape of IDH-targeted therapies, emphasizing the need for novel inhibitors and highlighting innovative strategies, including the design of smaller, more potent molecules with favorable pharmacokinetics and the potential of drug repositioning. We underscore that discovering new antitumor compounds targeting IDH requires a collaborative effort across biomedical fields. These advancements aim to overcome resistance, broaden therapeutic options, and improve the effectiveness of IDH-targeted treatments.
Retraction Notice to "Anti-proliferative, Morphological and Molecular Docking Studies of New Thiophene Derivatives and their Strategy in Ionic Liquids Immobilized Reactions".
Mohareb RM, Mukhtar S, Parveen H … +2 more , Abdelaziz MA, Alwan ES
Anticancer Agents Med Chem · 2025 · PMID 40958709 · Publisher ↗
We regret to inform you that the article titled "Anti-proliferative, Morphological and Molecular Docking Studies of New Thiophene Derivatives and their Strategy in Ionic Liquids Immobilized Reactions," published in Volum...
We regret to inform you that the article titled "Anti-proliferative, Morphological and Molecular Docking Studies of New Thiophene Derivatives and their Strategy in Ionic Liquids Immobilized Reactions," published in Volume 24, Issue 9, 2024 of Anti-Cancer Agents in Medicinal Chemistry (10.2174/0118715206262307231122104748), is being retracted. After a thorough investigation, it was found that there was potential data manipulation in the spectral data provided in the manuscript. The integrity of the data presented in the study could not be verified, leading to the decision to retract the article. We apologize for any inconvenience this may have caused and appreciate your understanding in this matter. Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure, or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.
Targeting WWPI HECT Domain by Small Inhibitors for Restoring PTEN Tumor Suppressive Role in Glioblastoma Therapy.
Ullah A, Khan M, Rahman SU … +8 more , Qayum U, Rehman NU, H Abdellattif M, Elshamy MMA, Alnjaa AA, Ahsan Halim S, Khan A, Al-Harrasi A
Anticancer Agents Med Chem · 2025 Sep · PMID 40947713 · Publisher ↗
INTRODUCTION: PTEN (Phosphatase and tensin homolog) is a valuable regulator of the PI3K-AKT and mTOR pathways and is frequently mutated in cancer-like glioblastoma. The WWPI HECT domain has a group of enzymes called E3 l...
INTRODUCTION: PTEN (Phosphatase and tensin homolog) is a valuable regulator of the PI3K-AKT and mTOR pathways and is frequently mutated in cancer-like glioblastoma. The WWPI HECT domain has a group of enzymes called E3 ligases that ubiquitinate and inactivate PTEN by binding to it, which ultimately inhibits its lipid phosphatase function and promotes nuclear delocalization. This investigation seeks to restore the PTEN tumor suppressive activity by inhibiting the WWPI HECT domain in-silico. METHODS: We virtually screened a library of ~960 compounds in the active pocket of the human WWPI HECT domain, and fifteen compounds were chosen based on their favorable binding affinities and highly negative docking scores. RESULTS: Among those hits, five compounds, C5, C6, C8, C9 and C11, properly fit the standard with favorable pharmacokinetic and drug-like quality. Their capacity to suppress cell propagation was evaluated in the U87 glioma cell line. The compounds (C5, C6, C8, C9 and C11) exhibited significant anti-proliferative capability with IC50 values of 6.98 ± 0.14 μM, 14.58 ± 1.49 μM, 11.12 ± 0.73 μM, 13.85 ± 1.63 μM and 18 ± 1.23 μM, respectively. DISCUSSION: Strong inhibitory action against glioma cells was shown by the discovered compounds, especially C5 and C8, suggesting that they may be able to restore PTEN tumor suppressive capabilities. A potential therapeutic intervention mechanism for glioblastoma is suggested by their interaction with the WWPI HECT domain. CONCLUSION: This study has discovered novel inhibitors against the WWPI HECT domain, and a treatment option for glioblastoma.
Unveiling the Distinct Effects of a Two-Dimensional Copper/Sodium Complex: Oxidative Stress on Erythrocytes and Cytotoxicity, Apoptosis, Drug Resistance, and Inflammation in Lung Cancer Cells.
Li C, Majd MH, Heidari A … +2 more , Razmara Z, Guo D
Anticancer Agents Med Chem · 2025 Sep · PMID 40916440 · Publisher ↗
INTRODUCTION: Copper complexes, as endogenous metals, have potential in cancer therapy, addressing issues associated with cisplatin. Since cisplatin uses Copper Transporter 1 (CTR1) for cellular entry, copper complexes m...
INTRODUCTION: Copper complexes, as endogenous metals, have potential in cancer therapy, addressing issues associated with cisplatin. Since cisplatin uses Copper Transporter 1 (CTR1) for cellular entry, copper complexes may utilize this pathway to enhance transport efficiency. METHODS: The Cu/Na dipicolinic acid complex was synthesized to assess its cytotoxicity, induction of apoptosis, drug resistance, and inflammation in cancerous and normal lung cells. The effects of oxidative stress on erythrocytes were also examined. RESULTS: Cytotoxicity tests (MTT and SRB) showed superior inhibitory effects on A549 lung cancer cells compared to cisplatin, with no toxicity observed in MRC-5 normal lung fibroblast cells. Real-time PCR revealed increased caspase-3 expression (extrinsic apoptosis) for the complex compared to cisplatin, possibly due to CTR1- mediated entry. The complex did not induce drug resistance, as shown by AKT1 expression, and reduced TNF-α expression, preventing inflammation in normal cells. In contrast to cisplatin, the complex caused minimal oxidative stress in erythrocytes. DISCUSSION: It can be concluded that the Cu/Na dipicolinic acid complex may be easily transported by CTR1 to malignant tumors, particularly lung cancer. This complex has the ability to inhibit cancer cell growth and induce apoptosis in lung cancer cells. Therefore, copper complexes show promise as potential therapeutic options for treating this type of cancer. CONCLUSION: The copper/sodium complex demonstrates enhanced therapeutic efficacy in lung cancer cells, requiring lower doses than cisplatin, while being safer for normal cells and erythrocytes.
Luteolin Enhances Anticancer Effects of PX-478 during Hypoxic Response in Metastatic Breast Cancer Cells.
Dukel M, Zarzour F
Anticancer Agents Med Chem · 2026 · PMID 40916439 · Publisher ↗
INTRODUCTION: The presence of severe hypoxic stress can drive tumor growth, angiogenesis, and metastatic characteristics via up-regulated hypoxia-inducible factor 1-alpha (HIF-1α). Hence, targeting HIF-1α is considered a...
INTRODUCTION: The presence of severe hypoxic stress can drive tumor growth, angiogenesis, and metastatic characteristics via up-regulated hypoxia-inducible factor 1-alpha (HIF-1α). Hence, targeting HIF-1α is considered a promising strategy, as increased HIF-1α activity is a key factor in the aggressive phenotype of malignancies. In this study, we aimed to investigate the anti-cancer effects of several flavonoids, both single and in combination with PX-478, in breast cancer cell lines. METHODS: We tested the effects of luteolin and PX-478, both alone and in combination, on HIF-1α level in breast cancer cells under hypoxia using the cell viability assay. To determine the rationale for the cell growth inhibition induced by the luteolin+PX-478 combination, we conducted experiments to assess cell survival, apoptosis, cell cycle, invasion, and migration under both normoxic and hypoxic conditions. Furthermore, we evaluated the effect of this combination on DNA damage response under hypoxic stress via Comet assay and immunofluorescence staining. RESULTS: Our findings revealed that the luteolin+PX-478 combination significantly suppressed the growth of MDA-MB-231 cells. In addition, we assessed time-dependent expression of HIF1α in MDA-MB-231 cells and observed that the combination of luteolin and PX-478 down-regulated the HIF-1α level. Finally, we found that the luteolin+PX-478 combination induced apoptosis and G2 cell cycle arrest and enhanced DNA damage response. This combination also sensitized breast cancer cells to ionizing radiation in hypoxic stress. DISCUSSION: The findings suggested that targeting HIF-1α with a combination of luteolin and PX-478 may provide a synergistic approach to suppressing tumor growth and enhancing therapeutic response under hypoxic conditions. The observed effects on apoptosis, cell cycle arrest, and DNA damage response indicated that this combination could be a promising strategy for overcoming hypoxia-induced resistance in breast cancer therapy. CONCLUSION: Collectively, our results suggested the combination of luteolin and PX-478 to enhance the anticancer effects of PX-478 in breast carcinoma cells by impeding the cell growth and inducing DNA damage response under hypoxia.
The Promising Role of PKM2 in the Diagnosis and Prognosis of Ovarian Cancer.
Borra PK, Chandra P, Sharma H … +6 more , Fatima S, Koneru A, Athilli L, Fatima F, Kumar NB, Sachan N
Anticancer Agents Med Chem · 2025 Sep · PMID 40916418 · Publisher ↗
PKM2 has emerged as a critical biomarker with the potential to enhance both diagnostic accuracy and therapeutic strategies in ovarian cancer. Due to its high fatality rate and difficulty identifying early signs, ovarian...
PKM2 has emerged as a critical biomarker with the potential to enhance both diagnostic accuracy and therapeutic strategies in ovarian cancer. Due to its high fatality rate and difficulty identifying early signs, ovarian cancer remains a major global health concern. Biomarkers, particularly PKM2, provide targeted therapeutic methods and early detection. The complex role of PKM2 in cancer metabolism highlights its importance as a diagnostic biomarker, particularly through its involvement in the Warburg effect. Its interaction with key signaling pathways and tissue-specific expression patterns makes it a compelling target for personalized therapeutic strategies. Moreover, the detection of PKM2 in the blood of cancer patients further underscores its clinical utility and therapeutic relevance. Beyond diagnostics, PKM2 is also a promising therapeutic target. Preclinical research has reported that both activators and inhibitors of this protein are effective. For PKM2-based treatments to be successfully incorporated into clinical practice, extensive research and rigorous validation are required. To overcome the difficulties in managing ovarian cancer and accomplish the objective of improved early detection and individualised treatment methods, collaboration among the research, healthcare, and advocacy sectors is crucial. In conclusion, PKM2 represents a promising target in the fight against ovarian cancer, with the potential to improve diagnostic accuracy, therapeutic strategies, and overall patient survival.
Euxanthone Inhibits Hepatocellular Carcinoma Progression by Targeting the miR-199a-5p/E2F3 Regulatory Axis.
Al Awadh AA
Anticancer Agents Med Chem · 2025 Aug · PMID 40910242 · Publisher ↗
BACKGROUND: Hepatocellular carcinoma (HCC) ranks among the leading causes of cancer-related deaths on a global scale. This study aimed to evaluate the effects of euxanthone on the proliferation of HCC cell lines and eluc...
BACKGROUND: Hepatocellular carcinoma (HCC) ranks among the leading causes of cancer-related deaths on a global scale. This study aimed to evaluate the effects of euxanthone on the proliferation of HCC cell lines and elucidate the underlying molecular mechanisms. METHODS: HCC cell lines (HepG2, Huh-7, SNU-398, SK-HEP-1, Hep3B) and the normal liver cell line THLE-2 were cultured and treated with euxanthone at concentrations between 0 and 100 μM. Cell viability was evaluated using the MTT assay, while phase contrast microscopy and cell cycle analysis were performed to evaluate morphological changes and cell cycle distribution. qRT-PCR was utilized to measure miRNA and mRNA expression levels, while a dual luciferase reporter assay validated the interaction between miR-199a-5p and E2F3. RESULTS: Euxanthone significantly (P < 0.05) inhibited cell proliferation in all HCC cell lines, with IC₂⁽ values between 6.25 and 25 μM. HepG2 cells exhibited pronounced sensitivity, with an IC₂⁽ of 6.25 μM. Euxanthone induced a G1 phase arrest, characterized by decreased expression of Cyclin D1 and E, and increased levels of p21. Additionally, it upregulated miR-199a-5p, which was identified as a mediator of the antiproliferative effects by targeting E2F3. Euxanthone treatment also significantly (P < 0.05) inhibited HepG2 cell migration in a wound healing assay. CONCLUSION: Taken together, euxanthone exerts antiproliferative effects on HCC cells via the miR-199a-5p-E2F3 axis and inhibits cell migration. These findings support its potential as a therapeutic agent for HCC, highlighting the need for further investigation into its clinical applications.
Evaluation of Anticancer Potential in Human Colorectal Carcinoma Cells by Fungal-Mediated Zinc Oxide Nanoparticles.
Alqurashi YE, Almalki SG, Ibrahim IM … +5 more , Mohammed AO, Abd El Hady AE, Kamal M, Fatima F, Iqbal D
Anticancer Agents Med Chem · 2026 · PMID 40910209 · Publisher ↗
INTRODUCTION: Chemotherapy faces limitations such as toxicity and resistance, necessitating novel cancer treatments. Green-synthesized zinc oxide nanoparticles (ZnO-NPs) have attracted attention for their safety, biocomp...
INTRODUCTION: Chemotherapy faces limitations such as toxicity and resistance, necessitating novel cancer treatments. Green-synthesized zinc oxide nanoparticles (ZnO-NPs) have attracted attention for their safety, biocompatibility, and therapeutic potential. This study investigates the anticancer efficacy of ZnO-NPs synthesized using the extracellular matrix of against colorectal cancer cell lines . METHODS: ZnO-NPs were synthesized extracellularly using fungal extract. The nanoparticles were characterized through UV-Vis spectrophotometry, showing an absorbance peak at 375 nm, and scanning electron microscopy (SEM), which determined their morphology and size. The anticancer activity was evaluated in vitro using cells. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were assessed to understand the mechanism of cytotoxicity. studies were proposed for further validation. RESULTS: The synthesized ZnO-NPs appeared pale white and exhibited a characteristic absorbance at 375 nm. SEM revealed spherical particles ranging from 35-150 nm. The ZnO-NPs showed strong anticancer activity with an IC value of 40.6 μg/mL. ROS levels increased significantly in treated cells, while the MMP decreased to 77.25% compared to 100% in controls. DISCUSSION: ZnO-NPs exerted cytotoxic effects via ROS generation and mitochondrial dysfunction. These results underscore the nanoparticles' ability to induce apoptosis in cancer cells through oxidative stress pathways. CONCLUSION: Biogenically synthesized ZnO-NPs from A. biplanus show promise as eco-friendly anticancer agents. Further in vivo studies are recommended to confirm their therapeutic potential.
Microbial-Derived Anti-Cancer Compounds: Advances in Drug Discovery, Bioengineering, and Therapeutic Applications.
Tyagi E, Jain D, Bhuyan R … +1 more , Prakash A
Anticancer Agents Med Chem · 2026 · PMID 40908691 · Publisher ↗
INTRODUCTION: Microbial metabolites represent a valuable source of bioactive compounds with promising anticancer properties. However, conventional drug discovery approaches are time-intensive and resource-demanding. METH...
INTRODUCTION: Microbial metabolites represent a valuable source of bioactive compounds with promising anticancer properties. However, conventional drug discovery approaches are time-intensive and resource-demanding. METHODS: Recent developments in artificial intelligence (AI), machine learning (ML), molecular docking, and quantitative structure-activity relationship (QSAR) modeling have been examined for their role in the identification and optimization of microbial metabolites. RESULTS: AI-driven approaches have significantly enhanced compound screening and prediction of therapeutic efficacy. Nanocarrier-based drug delivery systems have improved the bioavailability, specificity, and stability of microbial metabolites while minimizing systemic toxicity. Despite these advancements, challenges remain in clinical translation due to the lack of validation and comprehensive pharmacokinetic data. DISCUSSION: This review highlights the integration of advanced computational tools and nanotechnology in accelerating the discovery and delivery of microbial-derived anticancer agents. CONCLUSION: Future directions should focus on integrating AI with synthetic biology to engineer microbial strains capable of producing enhanced bioactive compounds. Additionally, leveraging nanotechnology could refine targeted delivery mechanisms. A deeper understanding of molecular pathways and drug resistance mechanisms is essential to support the development of combination therapies. Overall, microbialderived compounds hold substantial potential in advancing precision oncology.
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