Anti-cancer Agents In Medicinal Chemistry[JOURNAL]
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200 papers
Nanosomal-Mediated Lipid Suspension Delivery of Docetaxel as a Promising Landscape to Enhance the Therapeutic Potential in Triple-Negative Breast Cancer.
Jha P, Anjum V, Choudhary R … +3 more , Kadi A, Ali F, Potoroko I
Anticancer Agents Med Chem · 2026 · PMID 40442909 · Full text
The challenging subtype of breast cancer known as Triple-Negative Breast Cancer (TNBC) is characterized by the absence of HER2 expression, progesterone receptors, and estrogen receptors. TNBC is linked to a harsh treatme...
The challenging subtype of breast cancer known as Triple-Negative Breast Cancer (TNBC) is characterized by the absence of HER2 expression, progesterone receptors, and estrogen receptors. TNBC is linked to a harsh treatment trajectory, elevated rates of recurrence, and restricted therapeutic alternatives. The mainstay of treatment for TNBC has historically been conventional chemotherapy, especially taxanes like Docetaxel. However, the effectiveness of these drugs is frequently compromised by systemic toxicity and resistance mechanisms. The development of Nanosomal Docetaxel Lipid Suspension (NDLS) offers a promising alternative, designed to enhance Docetaxel's therapeutic index by improving solubility, reducing side effects, and optimizing tumor-targeted drug delivery. NDLS has potential as a delivery system for additional chemotherapy drugs or combination treatments. This study addresses the cellular and molecular causes of TNBC, emphasizes the drawbacks of traditional treatments, and offers a thorough examination of NDLS in preclinical and clinical settings. This review provides a thorough analysis of NDLS in TNBC, laying the groundwork for further studies and therapeutic applications.
The Role of Cisplatin Prodrugs Bonded to Polymer Carriers for Nanodrug-targeted Treatment of Hepatocellular Carcinoma.
Li Z, Luo L, Wang Z … +1 more , Hou J
Anticancer Agents Med Chem · 2025 · PMID 40442908 · Publisher ↗
BACKGROUND: The toxic effects of cisplatin limit its therapeutic efficacy on hepatocellular carcinoma (HCC). Cisplatin(IV) (Pt(IV)) with better stability needs an effective drug delivery strategy. Here, we explored the t...
BACKGROUND: The toxic effects of cisplatin limit its therapeutic efficacy on hepatocellular carcinoma (HCC). Cisplatin(IV) (Pt(IV)) with better stability needs an effective drug delivery strategy. Here, we explored the toxic and inhibitory effects and cell Pt contents of monomethoxyl poly(ethylene glycol)-block-poly(ecaprolactone)- block-poly(L-lysine) (MPEG-b-PCL-b-PLL)/Pt(IV) micelles (M(P3)) on HCC, and evaluated the therapeutic effect of (M (Pt (IV)) on HCC and . METHODS: We successfully constructed HCC model in BALB/c mice and prepared M(P3). The H22 and HepG2 cells were incubated with cisplatin, M(P3), and cisPt(IV)-(COOH) at 2, 10, 20, 50, 100 and 250 μM equivalent platinum (Pt) concentrations for 48 h and at 5 μM for 2/6 h. The HCC mice received cisplatin, M(P3), and cisPt(IV)-(COOH) (5 mg equivalent Pt/kg, once a week) for five weeks. The cell activity was assessed by MTT assay. The Pt contents were assayed by an inductively coupled plasma mass spectrometer (ICP-MS). The liver tumor weight was measured. The levels of liver tumor hepatorenal function indicators and malignant indicators were estimated by biochemical analysis and Western blot. RESULTS: The activity of H22 and HepG2 cells: cisPt(IV)-(COOH)2-treated > M(P3)-treated > cisplatin-treated. The Pt contents of H22 and HepG2 cells: M(P3)-treated > cisplatin-treated > cisPt(IV)-(COOH)2-treated cells. The hepatorenal function of HCC mice: M(P3)-treated > cisPt(IV)-(COOH)2-treated > cisplatin-treated. According to the weight and levels of malignant indicators of liver tumor, the therapeutic effect on HCC mice: cisplatintreated > M(P3)-treated > cisPt(IV)-(COOH)-treated. CONCLUSIONS: Although the inhibitory effect of M(P3) on HCC is not as good as cisplatin, M(P3) has significantly lower hepatorenal toxicity and remarkably higher cell Pt contents.
Maternal Embryonic Leucine Zipper Kinase (MELK) as a Promising Therapeutic Target in Triple Negative Breast Cancer.
Das A, Grewal AS, Agarwal P … +2 more , Pandita D, Lather V
Anticancer Agents Med Chem · 2025 · PMID 40417748 · Publisher ↗
INTRODUCTION: Maternal Embryonic Leucine Zipper Kinase (MELK) is a serine/threonine protein kinase involved in regulating key cellular processes, including cell cycle progression, apoptosis, embryonic development, splice...
INTRODUCTION: Maternal Embryonic Leucine Zipper Kinase (MELK) is a serine/threonine protein kinase involved in regulating key cellular processes, including cell cycle progression, apoptosis, embryonic development, spliceosome assembly, and gene expression. Notably, MELK is overexpressed in Triple-Negative Breast Cancer (TNBC), an aggressive malignancy associated with poor prognosis, high drug resistance, and limited treatment options. Given its critical role in TNBC pathogenesis, MELK has emerged as a potential biomarker and therapeutic target. This review explores the molecular functions of MELK, its involvement in oncogenic signaling pathways, and the development of MELK-targeting small-molecule inhibitors. METHODS: A comprehensive literature review was conducted to evaluate current knowledge on MELK, including its molecular functions, interactions within signaling pathways, role in TNBC progression, and potential as a therapeutic target. Relevant databases, including PubMed, Web of Science, Embase, and Scopus, were searched for studies related to MELK expression, signaling mechanisms, and experimental therapeutic approaches. RESULTS: MELK plays a central role in oncogenic signaling pathways that drive TNBC proliferation and survival. Preclinical studies have demonstrated that MELK inhibition can suppress TNBC cell growth and enhance chemotherapy efficacy. Several small-molecule inhibitors targeting MELK have shown promising anti-tumor activity in preclinical models. However, challenges remain in translating these findings into clinical applications due to drug specificity limitations and resistance mechanisms. CONCLUSION: MELK is a promising biomarker and therapeutic target in TNBC. However, further research is required to refine MELK inhibitors, enhance clinical efficacy, and overcome drug resistance mechanisms. Targeting MELK could offer a novel therapeutic strategy to improve TNBC treatment outcomes.
Combined Effects of Curcumin and Carboplatin on Mitochondrial Depolarization and Caspase Activation in Human Lung Adenocarcinoma Cells.
Kececi YO, Oktay ME, Incesu Z … +1 more , Ozdemir F
Anticancer Agents Med Chem · 2025 · PMID 40377150 · Full text
BACKGROUND: In various kinds of cancer, including Non-Small Cell Lung Cancer (NSCLC), treatment resistance diminishes the effectiveness of current therapeutic approaches and underscores the need for new treatment strateg...
BACKGROUND: In various kinds of cancer, including Non-Small Cell Lung Cancer (NSCLC), treatment resistance diminishes the effectiveness of current therapeutic approaches and underscores the need for new treatment strategies. AIMS: This study aimed to investigate the combined and individual effects of the anticancer drug carboplatin and the natural antioxidant curcumin, as well as the apoptotic effects of these drugs on the A549 cancer cells. OBJECTIVES: The synergistic effect of the combined treatment with curcumin and carboplatin on lung cancer cells was evaluated, focusing on early apoptosis, caspase-3/9 activity, and mitochondrial membrane potential. METHODS: The cytotoxic effects were determined using the MTT method. Apoptotic changes were examined using the Annexin V-FITC labeling method. Activation of caspases-9 and -3 and mitochondrial membrane potential were measured using flow cytometry. RESULTS: The IC values of curcumin and carboplatin against A549 cells were determined to be 60±8 μM and 100±9 μM, respectively. The combination of curcumin and carboplatin showed a synergistic effect. After treating A549 cells with carboplatin, curcumin, or the combined use of curcumin+carboplatin for 12 hours, the rates of early apoptotic cells were determined to be 9.5±1.3%, 8.1±0.3%, and 22.2±2.9%, respectively. The rate of early apoptosis in combined use was significantly higher compared to individual use. Similarly, when the combined treatment of curcumin and carboplatin was compared to the administration of carboplatin alone, a higher level of mitochondrial membrane depolarization was observed. There was a slight increase in caspase 9 activity in the combined treatment group compared to the individual treatments. Furthermore, after treating A549 cells with the specified doses, the caspase 3 activity was determined for carboplatin (0.5±0.1%), curcumin (1.9±0.0%), and the combination of both (7.3±0.8%). CONCLUSION: These results indicated that the combined use of curcumin and carboplatin enhanced apoptosis and mitochondrial depolarization, demonstrating that the combined treatment of drugs reduced the toxic dose of carboplatin. However, further research is needed to comprehensively understand the potential of this effect in in vivo studies.
Computational Optimization and Analysis for the Discovery of New HER2 and CDK4/6 Drug Candidates for Breast Cancer.
Elmallah S
Anticancer Agents Med Chem · 2026 · PMID 40370237 · Publisher ↗
BACKGROUND: Breast cancer is an abnormal cell growth that develops in the breast and spreads throughout the body. Despite cancer being the second leading cause of death, survival rates are increasing as a result of progr...
BACKGROUND: Breast cancer is an abnormal cell growth that develops in the breast and spreads throughout the body. Despite cancer being the second leading cause of death, survival rates are increasing as a result of progress in cancer screening and therapy. Breast cancer is the most frequently diagnosed cancer type among women, but in most cases, there are no obvious symptoms. Screening mammograms can be used for early detection of cancer. The size of the tumor and the extent of cancer spread determine the type of needed treatment. There are different forms of treatment, where targeted therapy is generally the least harmful. It targets specific characteristics of cancer cells, such as human epidermal growth factor receptor 2 (HER2). Tyrosine kinase inhibitors are effective targeted treatment of HER2 positive breast cancer. A newer class has emerged, cyclin dependent kinase (CDK4/6), which is used to treat metastatic breast cancer. OBJECTIVES: Although CDK4/6 inhibitors class of therapy has revolutionized the treatment of metastatic breast cancer, some patients showed resistance and decreased efficacy. This study is the first to propose innovative computational strategies to improve the effectiveness and pharmacokinetic properties of existing HER2/CDK4/6 inhibitors anti-cancer agents. Through computer-aided drug design, the activity of existing breast cancer drug candidates has been tested. Structural modifications have been applied for in-silico optimization of their biological activity. METHODS: In this research, twenty-two analogues of the tested compounds have been proposed. Their biological activity and pharmacokinetic properties (ADMET) have been tested using BIOVIA Discovery Studio software. RESULTS: Out of the designed analogous compounds, seven proposed structures demonstrated superior efficacy compared to the original drugs. The research study docking studies revealed that modifications to lapatinib and tucatinib improved binding affinity to HER2 by 15-25%, with docking scores of -18.34 kcal/mol and -1.04 kcal/mol, respectively. Similarly, CDK4/6 inhibitors exhibited enhanced selectivity, with abemaciclib showing the highest binding energy of -13.2 kcal/mol. ADMET predictions suggested improved solubility and reduced toxicity risks compared to the original drugs. CONCLUSION: The research study results demonstrate that the synthesis of more lipophilic analogues of lapatinib or tucatinib and, likewise designing of fluorinated derivatives of CDK4/6 inhibitors play a crucial role in improving the efficacy of these anti-cancer agents. These findings highlight the potential of the proposed modifications as promising candidates for further pharmacological and and clinical validation.
Precision-engineered Carrageenan Gels: Boosting the Efficacy, Selectivity, and Release of Celecoxib for Lung Cancer Therapy.
Bhatt A, Purohit P, Abdellattif MH
Anticancer Agents Med Chem · 2026 · PMID 40357790 · Publisher ↗
BACKGROUND: Lung cancer is one of the most widespread malignancies among all types of cancers. There is uncertainty in its treatment because of the selectivity. The investigation is aimed to enhance therapeutic efficacy...
BACKGROUND: Lung cancer is one of the most widespread malignancies among all types of cancers. There is uncertainty in its treatment because of the selectivity. The investigation is aimed to enhance therapeutic efficacy through targeted improvements in drug selectivity and reduced toxicity by analyzing well-accepted cyclooxygenase (COX)-2, which is an enzyme target and a known therapeutic target for anti-inflammatory and antitumor agents. OBJECTIVE: The objective of the present research was to identify the most suitable counterpart for celecoxib, which would produce synergistic effects and improve the selectivity index, safety, and efficacy of targeting cancer cells. METHODS: The HOPE-62 cancer cell line and noncancerous LLC-MK2 cell line were used to analyze the activity of the prepared formulations. The effectiveness was compared by calculating the half-maximal inhibitory concentration (IC50) values of carrageenan, celecoxib, and celecoxib embedded with carrageenan. The release pattern of celecoxib from the carrageenan matrix was also determined by using a trans-diffusion cell; moreover, the binding sites of carrageenan and celecoxib were also evaluated through molecular docking studies. RESULTS: Carrageenan showed promising anticancer activity, with an IC value of 17.3±2 μM against the HOPE- 62 cell line. When blended with celecoxib (15.6±2 μM), the combination achieved enhanced efficacy and improved selectivity over celecoxib alone (IC of 10.3±1.5 μM). In noncancerous LLC-MK2 cells, the IC values were observed to be significantly higher: 1484 ±6 μM in the combined formulation and with IC values of 559±3 μM and 878±4 μM, respectively, in celecoxib and carrageenan alone. CONCLUSION: The carrageenan-embedded celecoxib exhibited a significant increase in the selectivity index from 32 to 144, which suggests enhanced anticancer activity with a favorable safety profile. Initially, sustained release of celecoxib from the blend was at a higher rate, but steadily maintained rates were. The docking studies also supported the synergistic activity of the combined form through separate interaction patterns without interfering with others. These findings underscore the therapeutic potential of excipient-drug blending strategies to achieve synergistic effects, excellent selectivity, and reduced toxicity in cancer treatments.
Talimogene Laherparepvec (T-VEC): Expanding Horizons in Oncolytic Viral Therapy Across Multiple Cancer Types.
Tan RB, Yap YH
Anticancer Agents Med Chem · 2026 · PMID 40329730 · Publisher ↗
Talimogene laherparepvec (T-VEC), the first FDA-approved oncolytic viral therapy, has transformed cancer immunotherapy since its 2015 approval for unresectable melanoma. Engineered from Herpes Simplex Virus type 1 (HSV-1...
Talimogene laherparepvec (T-VEC), the first FDA-approved oncolytic viral therapy, has transformed cancer immunotherapy since its 2015 approval for unresectable melanoma. Engineered from Herpes Simplex Virus type 1 (HSV-1) with deletions in ICP34.5 and ICP47 genes and GM-CSF insertion, T-VEC selectively replicates within the tumor cells, inducing lysis and releasing tumor-derived antigens while stimulating systemic antitumor immunity through dendritic cell activation. Although extensively studied for melanoma, its potential extends beyond this malignancy, with emerging applications in breast cancer, Head and Neck Squamous Cell Carcinoma (HNSCC), and other solid tumors. This review synthesizes T-VEC's mechanism of action, leveraging dysregulated Ras signalling, impaired interferon pathways in cancer cells, its clinical outcomes, and safety profile across these indications. While prior literature emphasizes melanoma monotherapy and combinations with immune checkpoint inhibitors, less attention has been given to its efficacy in non-melanoma cancers and synergistic potential with chemotherapy or radiation therapy. By exploring recent trials, such as T-VEC with neoadjuvant chemotherapy in triple-negative breast cancer and pembrolizumab in HNSCC, highlighting its versatility. Comparative analysis with other oncolytic viruses like HF-10, oncorine (H101), and measles virus variants positions T-VEC within the virotherapy landscape. Key challenges-systemic delivery, immune clearance, and biomarker development for patient selection-are addressed alongside strategies to enhance immune modulation through novel combinations. This review underscores T-VEC's expanding role in cancer treatment, offering clinicians' and researchers' insights to optimize its therapeutic horizons across diverse malignancies.
Unraveling the Resistance: Challenges and Advances in PARP Inhibitor Therapy for BRCA1/2 Breast Cancer.
Tang H, Chen J, Jiang K … +4 more , He J, Tang F, Li D, Wu Y
Anticancer Agents Med Chem · 2026 · PMID 40329729 · Publisher ↗
Breast cancer is the most prevalent malignant tumor among women globally, with breast cancer susceptibility genes (BRCA1 and BRCA2, BRCA1/2) mutations significantly increasing the risk of developing aggressive forms of t...
Breast cancer is the most prevalent malignant tumor among women globally, with breast cancer susceptibility genes (BRCA1 and BRCA2, BRCA1/2) mutations significantly increasing the risk of developing aggressive forms of the disease. Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have shown promise in treating BRCA1/2-mutated breast cancer by exploiting deficiencies in homologous recombination (HR) repair. However, the emergence of acquired resistance poses a significant challenge. Our study examines the mechanisms of PARPi resistance in BRCA1/2-mutated breast cancer, synthesizing recent clinical advancements and identifying key resistance pathways, including HR recovery, DNA replication fork stability, and epigenetic modifications. We also highlight potential strategies to overcome these challenges to PARPi resistance, such as combination therapies and novel targets. Our comprehensive analysis aims to inform future clinical practices and guide the development of more effective treatment strategies.
Baicalin Inhibits Lung Cancer Cell Proliferation and Migration ALOX12-Mediated Ferroptosis.
Jin Y, Wen J, Geng Z … +8 more , Wang L, Fang W, Zhao H, Yan X, Chen B, Hua H, Chen W, Lin J
Anticancer Agents Med Chem · 2025 · PMID 40326039 · Publisher ↗
BACKGROUND: Lung cancer remains a leading cause of cancer-related mortality worldwide, primarily due to late-stage diagnosis and resistance to conventional therapies. Recent studies have highlighted the potential of natu...
BACKGROUND: Lung cancer remains a leading cause of cancer-related mortality worldwide, primarily due to late-stage diagnosis and resistance to conventional therapies. Recent studies have highlighted the potential of natural compounds in enhancing the efficacy and reducing the side effects of conventional cancer treatments. Baicalin, a bioactive compound from Scutellaria baicalensis, exhibits significant anticancer properties. OBJECTIVES: This study aimed to investigate the role of baicalin in modulating lung cancer cell behavior through the arachidonate 12-lipoxygenase (ALOX12)-mediated ferroptosis pathway. METHODS: We employed cyber pharmacology and molecular docking techniques to predict and validate the interaction between baicalin and ALOX12. In vitro experiments were conducted on A549 lung cancer cells to assess the effects of baicalin on cell proliferation, migration, and invasion. The expression levels of ALOX12, reactive oxygen species (ROS), and ferroptosis markers, such as Glutathione Peroxidase 4 (GPX4) and Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4), were measured. RESULTS: Baicalin treatment significantly upregulated ALOX12 expression in lung cancer cells, and this upregulation was associated with a reduction in cell proliferation, migration, and invasion. Furthermore, baicalin-induced ferroptosis was characterized by increased ROS levels, iron accumulation, and elevated expression of GPX4 and ACSL4. These findings suggest that baicalin enhances ferroptosis through ALOX12 activation, synergistically inhibiting cancer cell growth. CONCLUSION: Baicalin significantly upregulated ALOX12 expression, promoted ferroptosis, and inhibited the proliferation and migration of A549 lung cancer cells. This finding provides evidence for the potential use of baicalin as a therapeutic agent for lung cancer and highlights the importance of ALOX12 in lung cancer treatment strategies.
Novel Dihydropyrimidinones Synthesized through Modified Biginelli Reaction as Eg5 Kinesin Inhibitors with Potential Anti-cancer Effects: and Studies.
Nejabat M, Moghadam SG, Eskandarpour V … +3 more , Nejabat M, Nasrollahzadeh MS, Hadizadeh F
Anticancer Agents Med Chem · 2025 · PMID 40325529 · Publisher ↗
BACKGROUND: Monastrol is a known kinesin Eg5 inhibitor. It is a dihydropyrimidine with 4-(mhydroxyphenyl) substituent. In contrast to taxols and vinca alkaloids, which, through targeting microtubules, affect both normal...
BACKGROUND: Monastrol is a known kinesin Eg5 inhibitor. It is a dihydropyrimidine with 4-(mhydroxyphenyl) substituent. In contrast to taxols and vinca alkaloids, which, through targeting microtubules, affect both normal and cancer cells, kinesin inhibitors selectively target cancer cells. OBJECTIVES: In this study, m-hydroxyphenyl in monastrol was replaced with imidazolyl substituent, which has better water solubility and is found in the structure of many drugs and biologically active compounds. The effects of synthesized compounds were also investigated. METHODS: Three series of monastrol-related dihydropyrimidinone derivatives were synthesized through a modified Biginelli reaction. The newly synthesized compounds were characterized by elemental analysis, LCMS, and NMR. Then, the structure-activity relationship (SAR) of synthesized compounds was evaluated by their toxicity, molecular docking scores, and results of molecular dynamic simulation. The compounds with more potential (4i, 4m, 5a, and 6a) were further investigated and for their anti-cancer effects. RESULTS: The synthesized compounds could effectively reduce the ATPase activity of kinesins, which was consistent with the observation of G2/M arrest of cells in flow cytometry and confocal microscopy results. In addition, an increase in cells in the sub-G1 phase, along with the enhancement of the Bax/Bcl-2 ratio and overexpression of caspases 3, 9, and 8, suggested the apoptosis-inducing effects of compounds. Moreover, compounds showed potent anti-angiogenic effects via altering the expression of genes involved in angiogenesis, which was consistent with the reduced length of capillaries in the CAM test. The synthesized compounds could also demonstrate satisfactory results in the mice tumor model, which was in accordance with the findings of in vitro experiments. CONCLUSION: Novel dihydropyrimidinone derivatives synthesized via modified Biginelli reaction present promising potential as anti-cancer agents.
Enhanced Apoptosis in Pancreatic Cancer Cells through Thymoquinone-rich L. Methanol Extract: Targeting NRF2/HO-1 and TNF-α Pathways.
Cetinkaya S, Ayan IC, Dursun HG … +4 more , Suntar I, Taban K, Gok HN, Atak M
Anticancer Agents Med Chem · 2025 · PMID 40304335 · Publisher ↗
AIMS: This study explores the therapeutic potential of Nigella sativa L. and its key bioactive compound, thymoquinone (TQ). BACKGROUND: Pancreatic cancer presents a significant health challenge due to its aggressiveness...
AIMS: This study explores the therapeutic potential of Nigella sativa L. and its key bioactive compound, thymoquinone (TQ). BACKGROUND: Pancreatic cancer presents a significant health challenge due to its aggressiveness and limited treatment options. N. sativa and its component TQ have demonstrated anticancer properties in other cancers, warranting exploration in pancreatic cancer models. OBJECTIVE: To assess the antiproliferative, apoptotic, and anti-invasive effects of N. sativa extracts and TQ on pancreatic cancer cells, with a focus on modulating the NRF2/HO-1 and TNF-α signaling pathways. METHODS: MIA PaCa-2 and PANC-1 pancreatic cancer cell lines were treated with essential and fixed oils, methanol extracts (from Türkiye and Syria), and TQ. Cell viability, apoptosis, and invasiveness were assessed via XTT, Annexin V, and Matrigel assays, respectively. Gene expression and cytokine levels were evaluated using RT-qPCR and ELISA. HPLC was conducted to confirm TQ concentrations in extracts. RESULTS: The methanol extract of Türkiye-originated N. sativa seeds (TM) exhibited the highest cytotoxic effect, reducing cell viability in MIA PaCa-2 and PANC-1 at 0.05 mg/mL, while TQ significantly decreased viability at 20 μM. TM reduced MIA PaCa-2 and PANC-1 invasiveness (42 ± 1.23 and 35 ± 0.73, respectively) and contained a higher concentration of TQ (7.9168 ± 0.0561%) compared to the Syria-originated extract (SM). CONCLUSION: The findings suggest that TM and TQ exhibit strong anticancer potential by modulating key signaling pathways in pancreatic cancer cells, supporting their potential for further development as therapeutic agents in pancreatic cancer treatment.
Synthesis and Biological Studies of Aurones Derivatives for its Anticancer Potential.
Yogesh KP, Ingale PL
Anticancer Agents Med Chem · 2026 · PMID 40289977 · Publisher ↗
BACKGROUND: Aurone based compounds exhibited antioxidant and anti-inflammatory potential and documented for their anticancer potential. The anticancer potential of aurone derivatives AU3, AU4, AU5, AU7, and AU10 is yet t...
BACKGROUND: Aurone based compounds exhibited antioxidant and anti-inflammatory potential and documented for their anticancer potential. The anticancer potential of aurone derivatives AU3, AU4, AU5, AU7, and AU10 is yet to be studied against breast cancer. OBJECTIVE: The present work was undertaken to evaluate the anticancer potential of aurone based test compounds AU3, AU4, AU5, AU7, and AU10 in breast cancer cell lines MCF-7. METHODS: The azaindole based aurones were synthesized by the condensing 4,6-dimethoxybenzofuran-3(2H)-one derivative with various indole aldehydes in the presence of sodium hydroxide. The MCF-7 breast cancer cell line was used to assess the cytotoxic effects of these compounds. Molecular docking studies of the synthesized compounds against the Cyclin-dependent kinase 2 (CDK2)/Cyclin A complex were conducted. RESULTS: Our experimental findings demonstrated that AU3, AU4, AU5, AU7, and AU10 elicited significant effects on MCF-7 by virtue of its minimum cell viability, with IC50 values of 70.14 μM, 87.85 μM, 133.21 μM, 52.79 μM, and 99.55 μM, respectively, thus, exhibits potential anticancer action. Further, to corroborate the anticancer potential, we investigated mechanisms of action through molecular docking studies with the CDK2/Cyclin A complex (PDB: 6GUC) and their findings demonstrated that test compounds showed robust binding through various interactions, including hydrogen bonds, Pi-interactions, and Alkyl bonds with key residues such as Lys129, Asp127, Gln131, and Asp145. Test compounds AU3 and AU7, exhibited better binding affinities and diverse interaction profiles, suggesting a potent disruption of CDK2/Cyclin A activity. CONCLUSION: Thus, in conclusion, our findings revealed that AU3, AU4, AU5, AU7, and AU10 elicited anticancer action and their effects through CDK2/Cyclin A disruption.
Identification of Flavonoid-based Hypoxia-inducible Factor-2 Alpha Inhibitors for the Treatment of Breast Cancer- and Evidence.
Shahinaz, Baba M, Gor R … +4 more , Ramamurthy C, Mohideen HS, Ramalingam S, Vijayakumar TM
Anticancer Agents Med Chem · 2025 · PMID 40289350 · Publisher ↗
BACKGROUND: Breast cancer (BC) is a common malignancy that poses a serious threat to women's health. The hypoxic tumor microenvironment in BC promotes drug resistance, making hypoxia-targeted therapies crucial. Targeting...
BACKGROUND: Breast cancer (BC) is a common malignancy that poses a serious threat to women's health. The hypoxic tumor microenvironment in BC promotes drug resistance, making hypoxia-targeted therapies crucial. Targeting hypoxia-inducible factors (HIFs), particularly HIF-2α, has emerged as a promising approach to inhibit tumor growth and improve response to chemotherapy and radiotherapy. However, further research is required to fully understand the role of HIF-2α to develop more effective treatments for BC. AIMS: The aim of this study is to identify phytochemicals that target HIF-2α and evaluate their effects on the MCF-7 breast cancer cell line under hypoxic conditions. METHODS: Molecular docking identified phytochemicals targeting HIF-2α, with high-affinity compounds undergoing stability evaluation via GROMACS molecular dynamics simulations. ADMET and toxicity assessments were performed using SwissADME and ProTox-3.0. assays on hypoxic MCF-7 cells examined cell viability and gene expression. The expression of HIF-2α-regulated genes () was analyzed by using qRT-PCR. RESULTS: Molecular docking revealed that naringin (-8.2 Kcal/mol) and morin (-7.1 Kcal/mol) showed better binding affinity than the standard drug, belzutifan (-7.7 Kcal/mol). Dynamic simulations, including RMSD, RMSF, Hbond interactions, Rg, SASA, and PE, confirmed their strong binding potential. Morin, in particular, demonstrated more H-bond interactions and met Lipinski's Rule of Five, making it a promising candidate for in vitro studies. It reduced cell viability with an IC50 of 118 μM and significantly downregulated HIF-2α-associated genes. CONCLUSION: Morin demonstrated promising anti-cancer activity under hypoxic conditions by inhibiting HIF-2α in the hypoxia signaling pathway.
Methyl (Z)-2-(Isothioureidomethyl)-2-pentenoate Hydrobromide Induces Cell Cycle Arrest and Disrupts Mitosis in a Melanoma Cell Line.
Assuncao LS, Kretzer IP, Sierra Restrepo JA … +5 more , de Mello Junior LJ, Rocha Barbosa FA, Ferreira M, Mandolesi Sa M, Creczynski-Pasa TB
Anticancer Agents Med Chem · 2025 · PMID 40277100 · Publisher ↗
INTRODUCTION/OBJECTIVE: Cancer is a global health burden. Despite advances in early detection and therapeutics, cancer prevalence continues to increase, underscoring the need for innovative therapeutic strategies. Dysreg...
INTRODUCTION/OBJECTIVE: Cancer is a global health burden. Despite advances in early detection and therapeutics, cancer prevalence continues to increase, underscoring the need for innovative therapeutic strategies. Dysregulation of cell death mechanisms is a hallmark of cancer that can lead to apoptosis evasion, which strongly contributes to tumor progression and therapy resistance. Isothiouronium salts have attracted attention as promising antitumor agents. This study aimed to evaluate the in vitro antitumor effect of an isothiouronium salt (ISMF08) on the B16F10 melanoma cell line. METHODS: The antitumor properties of IS-MF08 were investigated by incubating B16F10 cells with the compound at different concentrations. Cytotoxicity was determined by the (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) (MTT) assay, cell cycle arrest and cell death mechanisms by flow cytometry, and morphological alterations by transmission electron microscopy. Physicochemical parameters related to druglikeness were predicted using the SwissADME tool. RESULTS: IS-MF08 was cytotoxic to melanoma cells, triggering cell cycle arrest and disrupting mitosis. The mechanism of cell death was compatible with apoptosis, as indicated by annexin V-FITC experiments and the relevant morphological changes in cell structure observed by transmission electron microscopy. SwissADME predicted that IS-MF08 has good physicochemical properties related to absorption and permeation. CONCLUSION: The numerous mechanisms of cell death triggered by IS-MF08 and its drug-likeness make it an interesting molecule in the search for new antitumor compounds, contributing to therapies targeting the dysregulation of cellular mechanisms such as apoptosis.
Advancements in Metal Complexation of Pyridine Derivatives (2022-2024): A Pathway to Enhanced Anticancer Potency.
Babteen NA
Anticancer Agents Med Chem · 2025 · PMID 40277099 · Publisher ↗
Cancer remains a major global health challenge, necessitating innovative therapies that selectively target cancer cells while sparing healthy tissues. Pyridine and its derivatives have gained prominence in medicinal chem...
Cancer remains a major global health challenge, necessitating innovative therapies that selectively target cancer cells while sparing healthy tissues. Pyridine and its derivatives have gained prominence in medicinal chemistry for their structural diversity and biological activity. However, their therapeutic potential is often hindered by low bioavailability, poor solubility, and rapid metabolism. Metal complexation has emerged as a promising solution, with pyridine nitrogen serving as an excellent coordination site for transition metals. These pyridinemetal complexes enhance stability, bioavailability, and anticancer properties, exhibiting potent cytotoxicity through mechanisms like ROS generation, DNA intercalation, and apoptosis induction. This review highlights the latest progress (2022-2024) in the field, emphasizing the structural modifications, and mechanistic insights that have propelled pyridine-metal complexes as potent anticancer agents. Special attention is given to the role of metal complexation in enhancing the anticancer potency of pyridine derivatives, with examples of preclinical studies showing their efficacy against various cancer types. The findings emphasize the potential of pyridine-metal complexes as a transformative approach in oncology, bridging the gap between innovative chemical design and impactful therapeutic applications.
BCL6 Inhibitors Exhibit Therapeutic Effects on Breast Cancer Cells through the BCL6-STAT4 Pathway.
Wang Z, Tan M, Zhang J … +2 more , Ren H, Ye X
Anticancer Agents Med Chem · 2025 · PMID 40257027 · Publisher ↗
OBJECTIVE: This study aimed to explore the roles of BCL6 and STAT4 in breast cancer, their biological functions, and their relationships with the prognosis of patients with breast cancer. METHODS: Online databases were u...
OBJECTIVE: This study aimed to explore the roles of BCL6 and STAT4 in breast cancer, their biological functions, and their relationships with the prognosis of patients with breast cancer. METHODS: Online databases were used to analyze the expression characteristics of BCL6 and STAT4 in breast cancer, as well as the correlation between STAT4 and both the prognosis of breast cancer patients and the biological function of breast cancer cells. BC cell lines, such as MCF7 and MDA-436 cells, were treated with the BCL6 inhibitor TP-021, and STAT4 and BCL6 mRNA expression levels were detected. Sh-RNAs were used to downregulate STAT4 in MCF7 and MDA-436 cells, and their proliferation ability was measured via a CCK-8 assay. RESULTS: BCL6 expression was detected in BC cell lines and tissues, but the expression of STAT4 was downregulated in BC, and the expression level of STAT4 was negatively correlated with patient prognosis. Inhibition of BCL6 can increase the STAT4 level in BC cells and inhibit their proliferation ability in vitro. Poor prognosis may be related to the expression of STAT4 and the characteristics of immune cell infiltration in tumor tissues. CONCLUSION: BCL6 inhibitors demonstrated therapeutic effects on breast cancer cells through the BCL6-STAT4 pathway.
Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel Benzothiazole-Based 1,3,4-Thiadiazole Derivatives as Potential Anticancer Agents.
Bedir BEO, Terzi E, Sanci TO … +4 more , Melfi F, Kaya Sezginer E, Kaya B, Cevik UA
Anticancer Agents Med Chem · 2025 · PMID 40237048 · Publisher ↗
OBJECTIVE: The present study aimed to design and synthesize a new series of benzothiazole analogues containing 1,3,4-thiadiazole, and assess their biological activities as potential anticancer agents. METHODS: N-(5,6-dim...
OBJECTIVE: The present study aimed to design and synthesize a new series of benzothiazole analogues containing 1,3,4-thiadiazole, and assess their biological activities as potential anticancer agents. METHODS: N-(5,6-dimethylbenzo[d]thiazol-2-yl)-2-((5-(substituted amino)-1,3,4-thiadiazol-2-yl)thio)acetamide derivatives (4a-4h) were synthesized via the reaction of thiadiazole derivatives (3a-3h) with 2-chloro-N-(5,6- dimethylbenzo[d]thiazol-2-yl)acetamide (1) in the presence of potassium carbonate. All the target compounds have been characterized by spectral analysis. The anticancer activities of compounds 4a-4h were tested against two human HT-1376 bladder and HT-29 colorectal carcinoma cells using the WST-1 assay. Flow cytometry was used for the determination of apoptosis, cell cycle, and caspase 3/7 activity. Moreover, wound-healing assay was utilized to evaluate cell migration. physicochemical, pharmacokinetics, and toxicological properties of compound 4g were determined by pkCSM, SwissADME, and SwissTargetPrediction online web tools. RESULTS: Among all synthesized derivatives, compound 4g (N-(5,6-dimethylbenzo[d]thiazol-2-yl)-2-((5-((3- methoxyphenyl)amino)-1,3,4-thiadiazol-2-yl)thio)acetamide) recorded the highest antiproliferative activity against HT-1376 cells with an IC as 26.51 μM at 24 h, which was less cytotoxic than cisplatin (IC=14.85 μM). The combined treatment with compound 4g and cisplatin increased the cellular apoptosis with a higher impact compared with the cisplatin group. The higher accumulation of cells in the G2 phase, a significant increase of caspase 3/7 activity, and the inhibition of migration rate were also observed in HT-1376 following a combination of compound 4g and cisplatin treatment versus cisplatin alone, which might be involved in the apoptotic effects of compound 4g. CONCLUSION: The in vitro anticancer potential of compound 4g lays the foundation for future research to focus on its value as a novel and advanced cancer therapy.
Recent Approaches on Oncolytic Viruses, Aptamers, TTFields and Personalized Treatment used for the Management of Glioblastoma: A Comprehensive Review.
Singh A, Kanda A, Kanda J
Anticancer Agents Med Chem · 2025 · PMID 40211994 · Publisher ↗
Glioblastoma (GB) remains a formidable challenge in oncology, with current treatment approaches providing only marginal improvements in patient outcomes. Despite significant advances in understanding its molecular and ge...
Glioblastoma (GB) remains a formidable challenge in oncology, with current treatment approaches providing only marginal improvements in patient outcomes. Despite significant advances in understanding its molecular and genetic characteristics, median survival for untreated patients remains distressingly low, emphasizing the urgent need for novel therapeutic strategies. This review comprehensively examines the standard first-line treatments for GB, including surgery, concomitant radio-chemotherapy, and maintenance chemotherapy, while highlighting the limitations of these approaches. Consequently, we explore emerging novel therapeutic modalities such as Oncolytic Viral Therapy with genetically modified oncolytic viruses that enhance the capabilities of antigen- presenting cells. These cells migrate to lymph nodes to recruit cytotoxic CD8+ T lymphocytes, directing them to the site of infection where they eradicate cells that promote tumour growth. Aptamer-based therapies, such as GMT-3, AS1411, GS24, GMT8, and Gint4.T, which exhibit specificity for their biological targets and can act as drug transporters by facilitating receptor-mediated transcytosis within the endothelial cells of the blood-brain barrier, thus improving drug delivery. Tumour-treating fields (TTFields) that have shown increased overall survival rates in patients. Personalized genomic medicine, driven by biomarkers, which provokes immune responses tailored to the tumour's specific antigens, thereby customizing patient-specific treatments to improve effectiveness. By synthesizing current evidence and recent breakthroughs, we underscore the potential use of advancing novel therapies to address the unmet clinical needs of GB patients and ultimately enhance their overall survival and quality of life.
Advanced Technologies for Cancer Immunotherapy: Focus on Gastrointestinal Cancers.
Ahangarzadeh S, Mohammadi E, Yaghoobi H … +5 more , Shahzamani K, Alagheband Bahrami A, Arezumand R, Beikmohammadi L, Alibakhshi A
Anticancer Agents Med Chem · 2025 · PMID 40211993 · Publisher ↗
Immunotherapy is becoming an alternative method for gastrointestinal cancers, such as colorectal, gastric, and liver cancers. This field of research focuses on utilizing the immune system to recognize and eliminate cance...
Immunotherapy is becoming an alternative method for gastrointestinal cancers, such as colorectal, gastric, and liver cancers. This field of research focuses on utilizing the immune system to recognize and eliminate cancer cells. One important method is immune checkpoint inhibitors, which enable T cells to recognize and attack tumor cells by releasing the immune system's brakes. Chimeric antigen receptor (CAR) T-cell therapy is another approach that modifies a patient's T cells to express receptors specific to tumor-associated antigens. Some cancer vaccines have demonstrated positive results in clinical trials, particularly colorectal and gastric cancers. Despite progress, challenges exist in immunotherapy for gastrointestinal cancers, such as treatment resistance, limited biomarkers for patient selection, and identifying new targets. In this review, different immunotherapy methods for all types of gastrointestinal cancers will be studied, and the limitations and benefits of each will be discussed in detail. By delving into the various immunotherapy methods, their limitations, and benefits, this review offers valuable insights that could potentially shape the future of gastrointestinal cancer treatment. It not only sheds light on the promising advancements in immune checkpoint inhibitors, CAR T-cell therapy, and cancer vaccines but also highlights the existing challenges that demand further research and innovation.
The Pivotal Role of Irradiation-induced Autophagy Mechanisms in Glioma Therapy.
Richard SA
Anticancer Agents Med Chem · 2025 · PMID 40211992 · Publisher ↗
Glioma epitomizes exclusively primary brain cancer of glial cell or neuroepithelial derivation and irradiation (IR) is one of the key and standard treatment modalities for all kinds of gliomas. Patients with glioma often...
Glioma epitomizes exclusively primary brain cancer of glial cell or neuroepithelial derivation and irradiation (IR) is one of the key and standard treatment modalities for all kinds of gliomas. Patients with glioma often undergo IR, such as whole-brain radiotherapy, stereotactic radiosurgery, as well as intensity modulated radiation therapy. However, IR therapy for malignant glioma is still facing severe hindrances because gliomas have high resistance to the IR. Autophagy is a type II programmed cell death which has been implicated in IR to gliomas. Autophagy was able to protect cells under sublethal damage circumstances, and it differentially triggered cell death after lethal damage in glioma. Furthermore, IR induced cerebral vascular damage was associated with progressive endothelial cells loss. IR triggered the acceleration of autophagic flux in cerebral endothelial cells which was characterized with robust upregulation of autophagy genes. Thus, autophagy plays a pivotal role in modulating the sensitivity and resistance of glioma cells to IR therapy. However, the exact autophagic mechanisms underlying radiosensitivity and/or radioresistance is still a matter of debate, and the development of effective radiosensitizers are lacking. Specific conditions pointing to the capabilities of IR-induced autophagy augmentation or inhibition of IR-induced cell death mostly contribute to radiosensitivity or radioresistance. Thus, IRinduced autophagy mechanisms in gliomas therapy are multiplex and they either induce radiosensitivity or inhibit radioresistance leading to potential effective treatment strategies for glioma. The aim of this review is to elucidate the autophagic mechanisms associated with radiosensitivity and/or radioresistance in glioma at the bench level, and accordingly highlight the development of potentially effective and efficient radiosensitizers to argument the treatment of glioma.
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