Anti-Cancer Agents in Medicinal Chemistry - Online First

Ovarian cancer (OC) is a lethal gynecological malignancy, with current therapies constrained by drug resistance and side effects. Autophagy plays a dual role in OC, while Traditional Chinese Medicine (TCM) monomers, as natural bioactive compounds, demonstrate significant potential in regulating autophagy and combating tumors. This review aims to summarize the mechanisms by which TCM monomers regulate autophagy in OC, providing a theoretical basis for TCM-based drug development and clinical applications.

Relevant literature was retrieved from databases including PubMed, Web of Science, and CNKI. The action targets and signaling pathways of TCM monomers were summarized to elucidate their mechanisms in regulating OC autophagy.

TCM monomers (e.g., ginsenoside Rg3, curcumin) bidirectionally regulate OC autophagy through pathways such as PI3K/AKT/mTOR and MAPK; some enhance chemotherapy sensitivity by inducing excessive autophagy or inhibiting protective autophagy.

TCM monotherapy offers unique advantages in the treatment of OC through precise regulation of autophagy. However, most studies are limited to in vitro experiments, and there is insufficient in vivo efficacy and clinical translational evidence.

Validating the complex action network of TCM monomers through multi-omics and clinical studies, and exploring their synergistic effects with conventional chemotherapy, is crucial for advancing the development of natural anti-ovarian cancer drugs.

Mentha spicata L. (Lamiaceae) has been used in traditional medicine to cure indigestion, stomach aches, and diarrhea. This research aims to synthesize silver nanoparticles from aqueous extract of M. spicata and to investigate its antioxidant, antibacterial, and anticancer activities.

The plant was extracted using maceration with water, and Mentha spicata-silver nanoparticles (MAgNPs) were prepared using a 5 mM silver nitrate solution. The antioxidant activity was assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide scavenging assays. Antibacterial analysis was done through the agar disk diffusion method. The anticancer potential was evaluated using the cytotoxicity and MTT assays.

The phytochemical screening revealed the presence of flavonoids and other phenolic compounds. The aqueous extract and silver nanoparticles scavenged the DPPH and hydrogen peroxide free radicals, with IC50 values of 1.556 mg/mL and 1.695 mg/mL, respectively. The bacterial strains were susceptible to the extract and silver nanoparticles, with inhibitory zones ranging from 4 to 11 mm. The zeta analysis revealed a size of 70.08 nm and a potential of -13.17 mV. The XRD showed a crystalline structure of silver nanoparticles. The FTIR revealed a characteristic N-H stretching frequency. The extract and nanoparticles exhibited cytotoxic and anti-proliferative effects in vitro against MDA-MB-231 cancer cells, with a significant difference among means (p < 0.05).

There is an urgent need to screen and standardize medicinal plants with medicinal benefits and less toxicity, which also serve as chelating agents in drug delivery.

The ability of the extract to scavenge free radicals and inhibit bacterial growth may be due to its chemical constituents. MAgNPs may be a viable option for potential application and development in cancer therapy.

During the last 20 years, the prevalence of colon cancer, among the most prevalent gastrointestinal cancers globally, has increased in the majority of nations. The current review compiled phytochemicals reported to manage colon cancer from 2015 to 2020.

The article is taken from various sources of Web of Science, PubMed, Google Scholar, Scopus, Elsevier, Research Gate, and PubChem.

Colon cancer is the leading cause of cancer-related death worldwide and impacts both men and women. Because of the present dietary habits and lifestyle, which include eating a lot of meat, drinking alcohol, and not exercising enough, the death rate from colon cancer has increased globally. A robust gastrointestinal tract and the control of regular intestinal activity seem to be significantly influenced by dietary fiber.

The prognosis for colon cancer is dismal, as it is frequently discovered at an advanced stage. Despite some evidence suggesting a diet low in fibre predisposes to colon carcinogenesis. The use of phytochemicals may help in the management of colon cancer.

By altering many signalling pathways involved in the control of chronic inflammation, the cell cycle, autophagy, apoptotic metastasis, and angiogenesis, these natural compounds have been shown to have anti-colon cancer properties. Compounds such as Ellagitannin, Ursolic acid, Garcinol, Oxymatrine, Emodin, Catalpol, Resveratrol, Zerumbone, Curcumin, Pyrogallol, α-Hederin, Juglone, Zingerone, Brosimone I, Organosilicon, Myricetin, Tenacissoside H, 6,8-Diprenylorobol, Plumbagin, Dioscin, and many more are listed with their mechanisms of action.

Heterocyclic compounds are widely utilized in the development of anticancer medications due to their diverse structures and ability to interact with multiple biological targets within cancer cells. Quinoline is a heterocyclic compound and an essential compound in the domains of industrial and pharmaceutical chemistry because of its various pharmacological effects. Researchers are developing new traditional, synthetic, and innovative green approaches to synthesize mono- or poly-substituted quinoline derivatives for anticancer activity.

A comprehensive literature survey was conducted using multiple databases, including Google Scholar, PubMed, SpringerLink, ScienceDirect, and others, to investigate the existing literature on synthetic strategies for various quinoline derivatives. This review article intends to present a summary of various traditional synthetic methods alongside innovative green approaches.

Many researchers have demonstrated that quinoline derivatives can be synthesized using various methods, including traditional techniques, hybrid approaches with heterocyclic structures, and innovative green synthetic methods, as well as elucidating their structure-activity relationships for potential use as anticancer agents. The majority of traditional synthetic methods rely on hazardous chemicals, low reaction rates, high temperatures, and high pressures. Currently, the green chemistry approach produces eco-friendly, economical, high-yield, pure, and outstanding products in the fields of industry and pharmaceuticals.

This section explores various affordable and eco-friendly synthetic techniques that produce potent and specific quinoline compounds, intended for use as anticancer agents.

The progress demonstrated in the green synthetic methods and the development of quinoline-based compounds as new treatment options could aid in identifying new and effective quinoline derivatives for cancer treatment in the future.

Estrogen receptor (ERa) is known to be a legitimate therapeutic target for the treatment of ER-positive breast cancer. Although selective estrogen receptor degraders (SERDs) like fulvestrant suppress ER signaling, their limited bioavailability challenges efficacy. Additionally, activating mutations in the ERa mediate resistance to endocrine therapy.

To elucidate the structural activity relationship within a chromene-based scaffold, we conducted pharmacophore mapping and Gaussian field-based 3D QSAR modelling. The most active analogue was docked into the ERa ligand binding domain (PDB ID: 6V8T) and then subjected to molecular dynamics simulations and molecular mechanics generalized born surface area (MM/ GBSA) binding-free energy calculations.

The pharmacophore mapping produces a five-point hypothesis, of which HHHRR_1 achieved the highest survival score (6.423) with a fitness score close to 3. Using HHHRR_1, a Gaussian Field-based 3D QSAR model with strong internal predictivity (cross-validated q² is 0.8) and an excellent external validation was developed (r² is 0.94). Compound 18 demonstrated stable binding in the ERa pocket with a ΔGbind MM/GBSA value of -67.03 kcal/mol, outperforming fulvestrant with a ΔGbind MM/GBSA of -64.76 kcal/mol. These findings suggest compound 18 engages critical ERa interactions more effectively with the target.

The integrated modelling approach, like pharmacophore mapping, 3D QSAR, docking, and molecular dynamics, elucidated molecular characteristics essential for potent ERa degradation. Compound 18, having superior binding affinities, implies that optimizing these features on a chromene scaffold can yield new oral SERDs with enhanced therapeutic potential.

Based on the results of pharmacophore mapping, docking, molecular simulation, and 3D QSAR studies, we have designed a new set of chromene scaffold-based derivatives as potent SERDs along with their predicted activity.

Prostate cancer is a leading cause of cancer-related mortality in men worldwide, and the treatment of metastatic castration-resistant prostate cancer (mCRPC) remains a major clinical challenge. CD24, a glycosylated cell surface protein, plays a critical role in tumor progression and immune evasion. This review focuses on the role of CD24 in prostate cancer pathogenesis, particularly its interaction with mutant p53, and explores potential therapeutic implications.

Through a systematic search of the PubMed, Web of Science, and Embase databases (2015–2025), using the following structured search terms: (CD24 OR “CD24 antigen”) AND (“prostate cancer” OR “prostatic neoplasms”) AND (“mutant p53” OR “TP53 mutation”) AND (“targeted therapy” OR immunotherapy), relevant studies were identified and screened according to PRISMA guidelines.

CD24 overexpression was significantly associated with high Gleason scores, metastasis, and poor prognosis. Mechanistically, CD24 promotes tumor progression by destabilizing p53 through the disruption of ARF-NPM interactions and by synergizing with mutant p53. Preclinical studies indicate that therapies targeting CD24, such as CAR-T cells and nanoparticle-based drug delivery systems, demonstrate potent anti-tumor effects.

The CD24–p53 axis is amplified in mCRPC and interacts with androgen receptor signaling, while tumor microenvironment factors further enhance treatment resistance.

CD24 and mutant p53 represent promising therapeutic targets in metastatic castration-resistant prostate cancer (mCRPC). Translating these targeting strategies into clinical practice may help overcome current therapeutic challenges and improve patient outcomes.

The emergence of acquired resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKIs) presents a significant barrier to effective treatment in lung adenocarcinoma. This study investigates the antitumor efficacy of FN-1501 and its potential synergistic interaction with Almonertinib (Alm) to combat this resistance.

The impact of FN-1501 on lung adenocarcinoma and its synergistic effects with Almonertinib (Alm) were assessed through flow cytometry, Western blot analysis, CCK-8 assays, and clonogenic formation assays. Additionally, transcriptome analysis and network pharmacology were employed to elucidate the functional mechanisms by which FN-1501 may reverse EGFR-TKI acquired resistance.

FN-1501 demonstrated the ability to inhibit cell proliferation, induce apoptosis, and arrest the cell cycle. The combination of Alm and FN-1501 restored sensitivity in resistant cell lines. Mechanistic investigations indicated that this combination triggered ferroptosis via the FOXO1-mediated upregulation of NCOA4. In vivo experiments showed that the Alm+FN-1501 combination significantly inhibited tumor growth compared to either treatment alone.

These results provide compelling evidence that targeting ferroptosis pathways could be a viable approach to overcoming resistance to EGFR-TKIs. The FOXO1/NCOA4 axis emerges as a critical component in this process, enhancing our understanding of the mechanisms underlying resistance. While these findings are promising, further research is needed to evaluate toxicity, pharmacokinetics, and the applicability of this strategy in a broader context of resistance. Identifying predictive biomarkers could help refine patient selection for this treatment approach.

FN-1501 exhibits significant antitumor activity and, when combined with Alm, effectively reverses EGFR-TKI resistance by inducing ferroptosis, highlighting its potential for clinical application.

Hypopharyngeal Squamous Cell Carcinoma (HSCC) is associated with a poor prognosis due to challenges in early detection, early metastasis, and limited treatment options.

This study aims to investigate the effect of metformin on HSCC and identify potential prognostic factors associated with this carcinoma.

The effects of metformin in HSCC cells were tested by functional assays in vitro. A xenograft tumor model was established, which was further examined by H&E staining, immunohistochemistry, and transmission electron microscopy (TEM). RNA sequencing analysis was employed to investigate the effects of metformin on gene expression and associated pathways. Bioinformatic analysis was further conducted to elucidate potential mechanisms and their correlation with gene expression, the tumor immune microenvironment, and survival prognosis. Finally, we further assessed the effect on FaDu cells by knocking down lncAROD using siRNAs.

The results demonstrated that metformin significantly reduced cell viability and migration, while promoting apoptosis and inducing cell cycle arrest in FaDu cells. WB analysis revealed that metformin inhibits the development of FaDu cells, possibly through the EMT pathway. In vivo studies indicate that metformin effectively inhibits tumor growth, promotes apoptosis, and autophagy. RNA-seq analysis revealed that metformin led to the upregulation of 1,697 genes and the downregulation of 858 genes, particularly highlighting a significant reduction in lncAROD, which were subsequently verified by qRT-PCR. Bioinformatic analysis demonstrated that lncAROD is highly expressed, with patients exhibiting higher levels of lncAROD showing poorer prognoses. Knockdown of lncAROD can reduce the proliferation, migration, and invasion of FaDu cells.

This finding presents a novel approach to the clinical management of HSCC, indicating that metformin influences various processes related to the growth and progression of HSCC. Specifically, it reduces lncAROD expression and inhibits tumor progression, suggesting that lncAROD may serve as a valuable biomarker for evaluating the prognosis of HSCC.

Approximately 30% of patients with diffuse large B-cell lymphoma (DLBCL) develop primary resistance or relapse, owing to the high heterogeneity and aggressive nature of the disease. Consequently, novel drugs are urgently needed to improve outcomes in patients who are resistant.

This study quantified the anti-proliferative effects of CCS1477 in vitro using the Cell Counting Kit-8 assay, 5‐ethynyl‐2′‐deoxyuridine staining, and lactate dehydrogenase measurement. Flow cytometry and Western blot analyses were performed concurrently to investigate the induction of apoptosis and the activation of mitophagy. The efficacy and safety of CCS1477 were evaluated in in vivo models. To elucidate the mechanism, cell lines with EP300 knockdown and overexpression were established. Functional assays and Western blot analyses revealed that EP300 regulates apoptosis, mitophagy, and c-MYC-mediated drug-resistant phenotypes.

This study demonstrated that CCS1477, a highly selective EP300/CBP bromodomain inhibitor, significantly suppressed the progression of diffuse large B-cell lymphoma. The study revealed that CCS1477 dose-dependently inhibited the proliferation of diffuse large B-cell lymphoma cells and induced apoptosis and mitophagy. Mechanistically, EP300 downregulation promoted apoptosis and activated the PINK1-dependent mitophagy pathway while suppressing c-MYC-mediated drug resistance genes, ultimately inhibiting DLBCL cell proliferation. In animal models, CCS1477 significantly reduced tumor volume and extended doubling time, providing the first evidence of its in vivo antitumor activity against DLBCL.

Through systematic in vitro and in vivo investigations, this study validated the significant therapeutic promise of EP300/CBP inhibitor CCS1477 for diffuse large B-cell lymphoma. However, the mechanistic basis for differential sensitivity across DLBCL subtypes, along with long-term efficacy and potential adverse effects, requires comprehensive investigation. Notably, EP300 has been verified as a novel prognostic biomarker and therapeutic target; this work establishes an innovative epigenetic-targeted strategy for relapsed/refractory diffuse large B-cell lymphoma.

By selectively targeting EP300, CCS1477 orchestrates a dual pro-death mechanism involving both intrinsic apoptosis execution and PINK1-driven mitochondrial clearance, resulting in significant inhibition of diffuse large B-cell lymphoma pathogenesis.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

This study has discovered novel inhibitors against the WWPI HECT domain, and a treatment option for glioblastoma.

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.

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.

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.

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.

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.

Lung cancer remains a leading cause of cancer-related deaths worldwide, with its incidence continuing to rise. Despite advancements in clinical treatments, their effectiveness is often restricted, emphasizing the need for novel therapeutic strategies. Natural products have long been explored for drug development, and among them, polysaccharides have gained significant attention due to their biocompatibility, biodegradability, and multiple biological functions.

A comprehensive review examined contemporary research on the anticancer properties of natural polysaccharides, focusing specifically on their effects in lung cancer. The analysis included studies investigating their influence on cancer cell growth, immune system modulation, and therapeutic outcomes. Evidence from laboratory (in vitro), animal (in vivo), and clinical studies was evaluated to provide a comprehensive overview of their potential role in lung cancer management.

Findings from recent studies indicate that polysaccharides can effectively inhibit the proliferation of lung cancer cells, thereby slowing tumor development. These compounds also appear to enhance immune responses by activating various immune cells and regulating cytokine production. Furthermore, polysaccharides have been shown to positively affect the gut microbiota, which may contribute to improved drug efficacy and a reduction in resistance to chemotherapy.

The evidence suggests that natural polysaccharides exert multifaceted effects in the context of lung cancer treatment. Their ability to directly suppress tumor growth, modulate the immune system, and interact with the gut microbiome positions them as promising adjuncts to existing therapies. However, the precise molecular mechanisms underlying these effects are not yet fully understood, and variability in study designs warrants cautious interpretation of the results.

Natural polysaccharides represent a promising complementary approach for lung cancer therapy, given their potential to inhibit tumor progression, enhance immune function, and improve the effectiveness of conventional drugs. Continued research is essential to fully elucidate their mechanisms of action and to translate these findings into effective clinical interventions.

VPS9 domain-containing 1 antisense RNA 1 (VPS9D1-AS1), also known as c-Myc-upregulated lncRNA (MYU) and FAK-interacting and stabilizing lncRNA (FAISL), is a novel long non-coding RNA (lncRNA) located at the human chromosome 16q24.3 locus. It has been reported to be highly expressed in various human cancers and associated with poor clinical pathological features and unfavorable prognosis in eight of the malignant tumors.

A comprehensive literature search was conducted using PubMed, Web of Science, and Google Scholar databases to identify relevant articles on “VPS9D1-AS1”, “MYU”, or “FAISL”. Only peer-reviewed publications were included, and articles related to oncology were specifically collected.

Mechanistically, VPS9D1-AS1 serves as a key regulator in four molecular models: signal, scaffold, guide, and decoy. These functions allow it to regulate the expression of target genes and activation of signaling pathways, thereby influencing the malignant phenotype of tumors.

The diverse molecular mechanisms of VPS9D1-AS1 highlight its significant role in the development and progression of various cancers. Its ability to act as a signal, scaffold, guide, and decoy suggests that it can influence multiple aspects of tumor biology, including proliferation, invasion, and metastasis.

VPS9D1-AS1 plays a significant role in the development and progression of various cancers through its diverse molecular mechanisms. Further research on VPS9D1-AS1 may provide valuable insights, which may facilitate the development of new diagnostic and therapeutic strategies for cancer.

Ursolic acid (UA) exhibits antitumor activity; however, its effects and mechanisms on triple-negative breast cancer (TNBC) cells are not well understood. The present study aimed to explore the anti-TNBC mechanisms of UA by network pharmacology and experimental validation.

TNBC cell lines MDA-MB-231 and BT-549 cells were treated with UA. A CCK-8 assay was performed to detect cell growth, while flow cytometry assessed cell cycle arrest and apoptosis. The underlying mechanism and potential targets of UA for TNBC treatment were investigated by network pharmacology, including PharmMapper database, GO, KEGG enrichment, and PPI analysis. The protein expressions and phosphorylation levels of FGFR1, AKT, and ERK were measured by western blot. Pull-down assay, cellular thermal shift assay (CETSA), and molecular docking were used to analyze the interaction between UA and FGFR1. Xenograft models were established to examine the effect of UA on TNBC tumor growth.

UA effectively reduced cell viability, induced apoptosis, and arrested cell cycle in TNBC cells. Moreover, UA significantly regulated the expression of Bcl-2 and Bax to induce apoptosis. The results of network pharmacology and western blot suggested that UA reduced FGFR1/AKT/ERK pathway. Furthermore, pull-down, CETSA, and molecular docking results revealed that UA directly bound to FGFR1. In the xenograft model, UA inhibited the growth by suppressing FGFR1.

In this study, we employed network pharmacology and experimental approaches to elucidate the mechanism of UA on TNBC. The results demonstrated that UA targeted FGFR1 to inhibit TNBC via mediating FGFR1/AKT/ERK pathway.

Our findings demonstrate that UA inhibits the FGFR1/AKT/ERK pathway by directly targeting FGFR1, thereby suppressing TNBC progression and supporting its potential as a therapeutic agent for TNBC treatment.

Benzochromenes are heterocyclic compounds of growing interest in medicinal chemistry due to their diverse biological activities, including antioxidant, anticancer, and antimicrobial properties.

A one-pot, three-component synthesis was employed to prepare benzochromene derivatives (4a–f) using 2-naphthol or its derivatives, active methylene compounds, and 2-methoxybenzaldehyde in ethanol with piperidine as a catalyst. The compounds were evaluated for their anticancer activity against MCF-7, HepG-2, and HCT-116 cell lines, as well as for their antimicrobial activity through molecular docking studies targeting cancer-related and microbial proteins.

All synthesized compounds were obtained in moderate to good yields. Compounds 4c, 4e, and 4f demonstrated superior biological activity compared to standard drugs Doxorubicin and Augmentin. Docking studies revealed strong binding affinities to key targets, including the TGF-βI receptor and the choline-binding domain.

The hydroxyl group at position 9 in compounds 4c and 4f likely contributed to enhanced antimicrobial activity, while the bromo group in 4e correlated with significant anticancer effects. These findings suggest meaningful structure–activity relationships and validate the design strategy.

The synthesized benzochromene derivatives exhibit promising anticancer and antimicrobial activities. Supported by molecular docking, these findings lay the groundwork for further pharmacological and in vivo evaluations of this scaffold.

Aromatase inhibition is one of the most effective strategy for the treatment of ER+ breast cancer, which accounts for about 70% of breast cancer cases. Indole-based aromatase inhibitors have altered the dynamics of the search for anti-breast cancer drugs with efficacy in nanomolar concentrations. In the present study, we have integrated pharmacophore mapping with Gaussian-based 3D-QSAR analysis to map the essential pharmacophoric features of indole-based aromatase inhibitors, aiming to optimize lead molecules.

Pharmacophore mapping and Gaussian-based 3D-QSAR were integrated to identify the steric and electrostatic features essential for aromatase inhibitory activity.

A Gaussian-based 3D-QSAR model with an r² value of 0.7621 and stability of 0.817 was generated to determine the nature of substitutions essential for optimal biological activity. Pharmacophore mapping results indicated that H-bond Donor (D), a Hydrophobic (H) feature, and three aromatic rings (R) are essential for potent inhibitory activity.

In order to identify important structural characteristics of indole-based aromatase inhibitors, the current study successfully integrated pharmacophore mapping investigations with 3D-QSAR. The designed molecule S1 demonstrated activity comparable to letrozole, with a predicted pIC50 value of 9.332 nM.

The designed compound S1 demonstrated a predicted IC50 value of 9.332 nM, comparable to the most active compound 15 and the standard reference Letrozole. The developed models may be utilized by medicinal chemists for the optimization of new indole-based aromatase inhibitors for the effective treatment of ER+ breast cancer.

Breast cancer develops in breast tissues, in ducts and lobules. It affects both genders, though it is uncommon in men. Hematological variations are important considerations and deficiencies in metals can negatively impact human health. Cadmium is highly toxic and plays role in breast cancer progression. This study was designed for hematological variations and cadmium induced toxicity in mice and humans causing breast cancer.

Mice, obtained from local supplier, housed at university laboratory for 11 weeks, exposed to cadmium. Following dissection, blood and organs were harvested for examination. Histological analysis of liver and mammary gland tissues was conducted.

Affected mice had higher Hb, RBC, HCT, MCV, and MCH, while humans showed lower Hb, HCT, and MCV but similar RBC and MCH. Other blood values also show changes. Histopathology revealed changes in mammary glands (higher cadmium led to increased fat deposition, degeneration of alveolar epithelial cells, and a reduction in alveolar milk lumen size, indicating compromised glandular function) and Liver damage (vacuolation, lipid accumulation, fibrosis, and collagen deposition, was noticeable with prolonged cadmium). These changes causes liver fibrosis and impaired mammary gland function.

The cadmium exposure induces distinct hematological alterations and severe tissues damage, reflecting species-specific responses. The observed liver fibrosis and mammary gland dysfunction emphasize cadmium’s potential to compromise critical organ functions over time.

Significant effects of cadmium exposure in mice were observed. Histological damage was seen in mammary glands and liver. Further research on protective measures and dose-response relationships for cadmium exposure is needed.

Current research focuses on identifying and analyzing bioactive metabolites with significant therapeutic properties derived from Punic granatum L. (Pomegranate) leaves. Methods: The biological potential of these metabolites was evaluated through anticancer activity. In contrast, LC-QTOF-MS and GC-QTOF-MS methods were used to profile the metabolites. In silico molecular docking was performed using various online and offline tools to validate the active metabolites.

PAC exhibited significant anticancer activity. The identified metabolites were screened, and 40 compounds from different categories were chosen for further in silico interaction studies.

The molecular docking analysis discovered lead molecules that exhibited promising binding energy scores, efficiency, and stable modulation with specific protein domains. However, clinical trials are required for the applications of the lead molecules in the design of anticancer drugs.

The findings from both in vitro and in silico analyses support the notion that the P. granatum Acetone Extract (PAC) is an excellent source of potential metabolites with therapeutic properties. According to the findings, this research enhances the treatment of human breast cancer and validates several plant traditions for their numerous benefits.

Cancer metastasis and associated thrombosis are significant contributors to cancer-related mortality, necessitating therapeutic strategies that simultaneously address both issues. This study aimed to evaluate the dual anti-metastatic and anti-hypercoagulability properties of dHG-5, a low-molecular-weight fucosylated glycosaminoglycan derived from the sea cucumber Holothuria fuscopunctata.

The heparanase-inhibitory and anticoagulant effects of dHG-5 were assessed in vitro using biochemical assays. The impact of dHG-5 on 4T1 cell migration and invasion was evaluated using Transwell assays. The anti-metastatic and anti-hypercoagulability efficacy of dHG-5 was further tested in a 4T1 mammary carcinoma mouse model, with enoxaparin (LMWH) used as a control.

dHG-5 exhibited potent heparanase inhibition (IC50 = 91.0 nM) and significantly reduced 4T1 cell migration and invasion at 4.0 µmol/L. In vivo, dHG-5 reduced lung metastasis without affecting tumor growth or proliferation. At a dose of 20 mg/kg, dHG-5 prolonged activated partial thromboplastin time (APTT) from 23.5 ± 1.85 s to 30.4 ± 3.36 s, effectively reversing hypercoagulability in tumor-bearing mice. Compared to low-molecular-weight heparin, dHG-5 selectively prolonged APTT with negligible effects on prothrombin time and thrombin time.

The findings highlighted the dual-action mechanism of dHG-5, namely inhibiting heparanase and selectively targeting the intrinsic coagulation pathway. This selective action minimized bleeding risk, a common issue with traditional anticoagulants. However, this study focused on a single cancer type and the use of a mouse model, which may not fully represent human pathophysiology. We would explore dHG-5's effects across different cancer types and investigate its potential synergistic effects with existing cancer therapies in the future.

dHG-5 suppressed metastasis and hypercoagulability through heparanase inhibition and selective action on the intrinsic coagulation pathway. These findings highlight dHG-5 as a promising dual-action therapeutic candidate for managing metastasis and cancer-associated thrombosis, offering a safer alternative to traditional anticoagulants.

Cyclooxygenase, an enzyme that occurs in at least two distinct variants (COX-1 and COX-2), is the target of classical inhibitors, which lack selectivity and inhibit both types of COX. However, a recent approach focuses explicitly on inhibiting COX-2, commonly found in inflamed tissue, resulting in fewer adverse effects than COX-1 inhibitors.

A series of 4-(4-(methylsulfonyl)phenyl)-6-phenylpyrimidin-2-amine derivatives were synthesized through a two-step process. First, 4-substituted acetophenones underwent base-catalyzed Claisen-Schmidt condensation with 4-(methylsulfonyl)benzaldehyde to yield chalcones, which were then cyclized with guanidine hydrochloride under basic reflux conditions. Molecular docking was performed using AutoDock Vina software. The inhibitory activities of COX-1 and COX-2 were evaluated using enzymatic assays. Antiplatelet aggregation was measured via a turbidimetric method, and antiproliferative activity was assessed using the MTT assay.

The in vitro experiments on COX inhibition revealed that a substantial number of the synthesized compounds presented a strong suppressive effect against COX-2. The assessment of antiplatelet aggregation activity indicated that most of the derivatives effectively inhibited ADP-induced platelet aggregation. Compound 4i exhibited the most potent antiproliferative activity, comparable to cisplatin. The docking studies and molecular modeling results demonstrated that the designed compounds, except for 4b, exhibited a binding behavior comparable to that of celecoxib. In addition, the insertion of the SO2Me moiety within the secondary binding site of COX-2 was observed.

These findings suggest that the structural modifications introduced in the synthesized derivatives contribute significantly to their selective COX-2 inhibition and antiplatelet properties. The correlation between docking results and biological assays supports the rationale behind the design of the compound.

The 4-(4-(methylsulfonyl)phenyl)-6-phenylpyrimidin-2-amine exhibits unique properties as a COX-2 inhibitor, displaying effective inhibition of COX-2 while showing minimal interaction with the COX-1 enzyme. Furthermore, our study revealed that most of these compounds exhibited inhibitory effects on ADP-induced platelet aggregation.

Melanoma, an aggressive skin cancer, has seen treatment advancements with immune checkpoint inhibitors (ICIs) like ipilimumab and nivolumab. Despite improved survival rates, resistance remains a challenge. The recent focus on lymphocyte activation gene-3 (LAG-3) inhibitors, such as relatlimab, shows promise in combination therapies, potentially improving outcomes with fewer adverse effects. This review evaluates the safety and efficacy of anti-LAG-3 antibodies in melanoma treatment.

This systematic review and meta-analysis, following the PRISMA guidelines and registered in PROSPERO (CRD42024565756), assessed anti-LAG-3 antibodies in melanoma treatment. A thorough search across PubMed, Embase, Scopus, and Web of Science up to January 2024 yielded relevant studies. Data on study characteristics, patient demographics, disease characteristics, treatment details, and clinical outcomes were extracted. Quality assessment was performed using the MINOR criteria. The meta-analysis, using STATA and random-effects models, addressed heterogeneity to determine safety and efficacy outcomes.

We examined the clinical benefit of this combination therapeutic approach by measuring several primary endpoints and running a meta-analysis to determine the pooled estimate of 6-month progression-free survival (PFS), 1-year PFS, 6-month duration of response (DoR), 1-year DoR, 1-year overall survival (OS), 2-year OS, partial response (PR), complete response (CR), objective response rate (ORR), disease control rate (DCR), stable disease (SD), and progressive disease (PD) for patients diagnosed with melanoma. Our analysis showed 66% of any grade treatment-related adverse events (trAEs) (95% CI: 51%-81%), 19% of grade ≥ 3 trAEs (95% CI: 11%-27%), 12% of any grade AEs leading to discontinuation (95% CI: 9%-14%), and 8% of grade ≥ 3 AEs leading to discontinuation (95% CI: 6%-10%). 76% of any grade overall AEs (95% CI: 34%-100%), and 33% of grade ≥ 3 overall AEs (95% CI: 15%-50%). The most common AEs were fatigue, pneumonitis, rash, pruritus, colitis, hepatitis, diarrhea, hypothyroidism, thyroiditis, and adrenal insufficiency.

This systematic review and meta-analysis provide comprehensive evidence regarding the safety and efficacy of anti-LAG-3 antibodies in melanoma therapy. Pooled data reveals encouraging outcomes across several key endpoints, including PFS, OS, and ORR. While trAEs were common (66% for any grade and 19% for grade ≥3), most were manageable.

Anti-LAG-3 therapy is an active and safe treatment that shows promising results in melanoma treatment.