Anti-cancer agents in medicinal chemistry最新文献

{"title":"Bioinformatics And Experimental Insights Into Sotorasib Resistance Mechanisms in Non-small-cell Lung Cancer.","authors":"Dongbing Li, Guizhen Lyu","doi":"10.2174/0118715206386488250728113358","DOIUrl":"https://doi.org/10.2174/0118715206386488250728113358","url":null,"abstract":"<p><strong>Introduction: </strong>This study aims to identify the key genes and pathways associated with sotorasib resistance in Non-Small Cell Lung Cancer (NSCLC) using bioinformatics analyses and experimental validation, with a focus on uncovering the potential mechanisms underlying resistance.</p><p><strong>Methods: </strong>We compared gene expression profiles between sotorasib-resistant (SR) and non-resistant NSCLC cell lines using the GSE229070 dataset and between NSCLC tissues and adjacent normal tissues using the GSE18842 dataset. Differentially expressed genes (DEGs) were identified and intersected across datasets using the Venn diagram package. Functional enrichment analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The transcriptional activity and prognostic impact of key genes were evaluated using the UALCAN portal and Kaplan-Meier Plotter, respectively. The correlation between gene expression and immune cell infiltration was analyzed using the TIMER database, and co-expressed genes were explored using LinkedOmics. qRT-PCR and Western blot were used to validate the expression of AREG in parental and SR cell lines.</p><p><strong>Results: </strong>We identified 33 overlapping DEGs, including TENM2, COL12A1, COL5A2, and LRRC15 (upregulated) and AREG (downregulated). AREG expression was significantly lower in NSCLC patients and associated with worse survival outcomes. AREG expression was also correlated with the levels of immune cell infiltration. Functional enrichment analysis revealed that AREG was associated with pathways including the NOD-like receptor signaling pathway, focal adhesion, DNA replication, and homologous recombination. Experimental validation confirmed that AREG mRNA and protein levels were significantly reduced in HCC78-SR cells compared to parental HCC78 cells.</p><p><strong>Discussion: </strong>The downregulation of AREG is closely associated with sotorasib resistance in NSCLC, potentially contributing to resistance through alterations in signaling pathways and the tumor immune microenvironment. This finding aligns with previous studies on AREG's role in drug resistance, highlighting its potential as a therapeutic target. However, limitations include reliance on publicly available datasets and the need for further validation in clinical cohorts.</p><p><strong>Conclusion: </strong>The study identifies AREG as a key gene associated with sotorasib resistance in NSCLC, suggesting its potential as a biomarker and therapeutic target. Further research is needed to elucidate the mechanisms underlying AREG's role in resistance and to explore its clinical significance.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"dHG-5 Exhibits Dual Efficacy of Anti-Metastatic and Anti-hypercoagulability in Mice by Inhibiting Heparanase and Intrinsic Coagulation Pathway.","authors":"Ziheng Tong, Zhipeng Xu, Wen Yang, Huaizheng Song, Shuguo Zheng, Lutan Zhou","doi":"10.2174/0118715206413123250612185241","DOIUrl":"https://doi.org/10.2174/0118715206413123250612185241","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer metastasis and associated thrombosis are significant contributors to cancerrelated 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.</p><p><strong>Methods: </strong>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 antimetastatic and anti-hypercoagulability efficacy of dHG-5 was further tested in a 4T1 mammary carcinoma mouse model, with enoxaparin (LMWH) used as a control.</p><p><strong>Results: </strong>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 lowmolecular- weight heparin, dHG-5 selectively prolonged APTT with negligible effects on prothrombin time and thrombin time.</p><p><strong>Discussion: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer Efficacy and Metabolomic Profiling of Punica granatum Leaf Extracts: In vitro and In silico Approaches.","authors":"Mital Kaneria, Kalpna Rakholiya, Disha Patel, Margi Patel, Mohd Abul Kalam, Rabbani Syed, Vijay G Sambad, Drashti B Padariya, Ankit Faldu, Dipak Kumar Sahoo, Ashish Patel","doi":"10.2174/0118715206374500250728064151","DOIUrl":"https://doi.org/10.2174/0118715206374500250728064151","url":null,"abstract":"<p><strong>Introduction: </strong>Current research focuses on identifying and analyzing bioactive metabolites with significant therapeutic properties derived from Punic granatum L. (Pomegranate) leaves.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>PAC exhibited significant anticancer activity. The identified metabolites were screened, and 40 compounds from different categories were chosen for further in silico interaction studies.</p><p><strong>Discussion: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Overview of the Therapeutic Potential of Pyrimidine Analogues in the Management of Colorectal Cancer.","authors":"Sathishkumar M, Dhunmati K, Ramalakshmi N, Nalini C N, Dibenthiran S, Indrakumar S","doi":"10.2174/0118715206381536250709201255","DOIUrl":"https://doi.org/10.2174/0118715206381536250709201255","url":null,"abstract":"<p><p>Colorectal cancer is the fourth most prevalent cause of cancer-related fatalities, and cancer is still one of the major causes of death globally. Although pyrimidine analogues can target abnormal cellular growth, they have demonstrated potential as therapeutic treatments for a variety of malignancies, including colon cancer. A vital nitrogen-containing aromatic heterocyclic molecule, pyrimidine is an important target for cancer treatments since it is involved in the construction of DNA and RNA. Recent research has investigated the synthesis and assessment of a number of pyrimidine derivatives, demonstrating their capacity to block particular enzymes and pathways linked to the development of cancer. According to the review, a number of pyrimidine-based chemical families, such as 1H-pyrazolo, diarylpyrazolo, and bromo-pyrimidine derivatives, have shown strong anti-cancer properties in preclinical models, especially against lung and colon cancer cell lines. Moreover, these compounds' structure-activity relationship (SAR) studies show that changes made at important positions on the pyrimidine scaffold improve their anticancer efficacy. These findings highlight the significance of further study into pyrimidine analogues as promising candidates for cancer therapy.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Potential of Next-generation Multi-functional Nanoplatforms for Breast Cancer.","authors":"Shreya Gupta, Tanmay J Urs, Navya Aggarwal, Shinjini Sen, Banashree Bondhopadhyay","doi":"10.2174/0118715206392103250715115020","DOIUrl":"https://doi.org/10.2174/0118715206392103250715115020","url":null,"abstract":"<p><p>The next-generation nanoparticles overcome the drawbacks of early nanoplatforms by integrating multiple functions, such as drug delivery, controlled drug release, and combination therapy, into a single system. This study examines the biomedical applications of quantum dots, carbon nanotubes, superparamagnetic iron oxide nanoparticles, and layered double hydroxides for the delivery of breast cancer drugs. They are termed as \"nextgeneration\" nanoparticles, as they are advanced nanocarriers that offer a comprehensive and alternative approach towards breast cancer treatment, providing enhanced specificity and efficacy compared to their predecessors. The development of these nanoplatforms has significantly enhanced drug bioavailability and reduced toxicity. A comprehensive analysis of a nanotechnology-based drug delivery system was conducted. The keywords used for this review were \"Breast Cancer\", \"Targeted Drug Delivery\", \"Quantum Dots\", \"Carbon Nanotubes\", \"Layer Double Hydroxides\", and \"Superparamagnetic Iron Oxide Nanoparticles\". The inclusion criteria consisted of studies focusing on breast cancer, targeted drug delivery, and therapeutic applications of these nanocarriers. In contrast, exclusion criteria included studies focusing on the synthesis of nanocarriers and the diagnostic applications of these nanostructures. The study underscores their mechanisms, limitations, and future development directions. Additionally, the study tracks the evolution of the nanocarriers since their early discovery. Next-generation nanocarriers (QDs, CNTs, SPIONs, and LDHs) have strong therapeutic potential owing to their precisely engineered properties, such as size, shape, morphology, and surface modifications. Their trigger-initiated drug release mechanisms enable targeted delivery with a better rate of tumor penetration, while their ability to co-deliver multiple therapeutic agents addresses drug resistance issues and provides synergistic effects. Comparative analyses have revealed that these advanced nanoplatforms significantly outperform early-generation carriers in terms of bioavailability, reduced toxicity, and treatment efficacy across various breast cancer types. Next-generation nanoplatforms offer unprecedented opportunities for targeted and efficient cancer treatment. Continued research and innovation are necessary to address existing challenges and to optimize their therapeutic potential for clinical applications.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Kinase Inhibitors in Cancer Neuroscience: Mechanisms, Therapeutic Potential, and Future Directions.","authors":"Manos C Vlasiou","doi":"10.2174/0118715206387712250711132221","DOIUrl":"https://doi.org/10.2174/0118715206387712250711132221","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer progression is increasingly understood to be influenced by neural mechanisms, including neurotransmitter signaling, neurotrophic factor activity, neuroinflammation, and neurogenic inflammation. These neurobiological interactions contribute to tumor proliferation, angiogenesis, and metastasis. Kinase inhibitors, a class of targeted therapies that block dysregulated kinase activity, have demonstrated promise not only in direct tumor suppression but also in modulating neural pathways associated with cancer progression.</p><p><strong>Methods: </strong>This review examines the role of kinase inhibitors in modulating cancer-associated neural mechanisms. A comprehensive literature search was conducted to identify studies exploring the effects of kinase inhibition on: (1) neurotransmitter signaling pathways; (2) neurotrophic factors such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF); (3) neuroinflammation through glial cell modulation; and (4) neurogenic inflammation. Additionally, we assessed the impact of kinase inhibitors on tumor-induced axonogenesis and stress-related signaling. Clinical relevance was evaluated through analysis of preclinical models, human case studies, and outcomes from relevant clinical trials.</p><p><strong>Results: </strong>Kinase inhibitors were found to significantly modulate neural factors that facilitate tumor growth. Specifically, they can suppress neurotrophic signaling (e.g., NGF/TrkA, BDNF/TrkB), inhibit glial activation, reduce pro-inflammatory cytokine production, and block neurotransmitter-induced proliferation. Inhibition of stress-responsive kinases such as p38 MAPK and JNK also disrupted tumor-associated axonogenesis and inflammation. Clinical trials demonstrate improved outcomes in cancers such as glioblastoma, breast cancer, and pancreatic cancer when kinase inhibitors are employed with consideration of neural mechanisms.</p><p><strong>Discussion: </strong>These findings support the emerging concept of targeting the neural tumor microenvironment as a therapeutic strategy. Kinase inhibitors represent a dual-action approach, suppressing both cancer cell intrinsic growth pathways and the neural factors that sustain them. However, several challenges persist, including resistance mechanisms, variability in patient neural profiles, and off-target effects. Future research should focus on the development of neural-specific kinase inhibitors, the use of neural biomarkers for therapy selection, and the integration of neuro-oncology into personalized treatment plans.</p><p><strong>Conclusion: </strong>Kinase inhibitors offer a promising frontier in cancer treatment by targeting neural mechanisms that contribute to tumor progression. While current evidence is encouraging, further investigation is required to optimize their use within neuro-oncology. Personalized approaches and novel targets within the neural-cancer axis will be essential for translating thi","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative Nanocarriers: Magnetosomes in the Fight against Cancer.","authors":"Shivani Yadav, Manoj Kumar Mishra","doi":"10.2174/0118715206377167250709062942","DOIUrl":"https://doi.org/10.2174/0118715206377167250709062942","url":null,"abstract":"<p><p>Recent advancements in medication formulations and drug delivery systems over the past two decades have improved patient adherence and pharmacological responses. Efficient, target-specific medication delivery remains challenging, with many current systems designed to minimize drug loss and degradation. Magnetosomes, as nanocarriers, show promise for delivering antibodies, vaccine DNA, and siRNA, enhancing the stability of chemotherapeutics, and enabling targeted delivery to malignant tumors. Targeted drug delivery is crucial in cancer treatment, as anticancer drugs often cannot differentiate between healthy and malignant cells, causing side effects and systemic toxicity. Magnetosome-based drug delivery offers a potential solution, minimizing adverse effects and promoting drug accumulation at the target site. This review covers the design, development, and advancements in magnetosome-based drug delivery for cancer therapy.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyamines in Cancer: Mechanisms, Metabolic Targets, and Therapeutic Opportunities.","authors":"Azmi Yerlikaya","doi":"10.2174/0118715206390332250711060007","DOIUrl":"https://doi.org/10.2174/0118715206390332250711060007","url":null,"abstract":"<p><strong>Introduction: </strong>Polyamine metabolism is essential for cancer cell growth, with enzymes like ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) playing key roles in polyamine (PA) biosynthesis. These polyamines (putrescine, spermidine, and spermine) regulate vital cellular processes, including DNA replication, protein synthesis, and cell cycle progression. Dysregulated polyamine metabolism is common in cancer, making ODC and AdoMetDC attractive therapeutic targets. This review highlights polyamines' role in cancer and explores combination therapies targeting polyamine metabolism and critical signaling pathways for improved clinical outcomes.</p><p><strong>Methods: </strong>A comprehensive analysis of both historical and recent literature on polyamine metabolism in cancer was performed using PubMed, which provides access to over 37 million citations from biomedical literature. Expression data for key polyamine biosynthetic enzymes, ODC and AdoMetDC, were obtained from the UALCAN portal - an interactive web resource for the analysis of cancer OMICS data. The IUPAC names of drugs and inhibitors targeting the polyamine pathway were retrieved from the PubChem database and used to generate molecular structures using the BIOVIA Draw 2025 program. Additionally, the ClinicalTrials.gov database was explored to identify ongoing and completed clinical research studies, as well as to gather detailed information on therapeutic agents targeting polyamine metabolism.</p><p><strong>Results: </strong>Aberrant polyamine metabolism in cancer is driven by oncogenic pathways like MYC, Akt, and mTOR. MYC upregulates <i>ODC1</i>, promoting polyamine dysregulation. Defects in enzymes such as MTA phosphorylase (MTAP) enhance cancer cell sensitivity to inhibitors of purine/pyrimidine synthesis and the ubiquitin-proteasome pathway, suggesting alternative therapeutic strategies.</p><p><strong>Discussion: </strong>Therapeutic strategies combining polyamine biosynthesis inhibition with targeting nucleotide synthesis or proteasome function have shown synergistic potential. However, the dual nature of polyamines - supporting both, tumor growth and ferroptotic cell death - poses a therapeutic challenge. Balancing these effects is key to designing effective interventions. Advancing this field requires not only selective inhibitors but also a deeper understanding of context-dependent polyamine functions in tumor biology.</p><p><strong>Conclusion: </strong>Developing more potent inhibitors with improved drug-like properties is crucial for advancing polyamine- targeted therapies and positioning this field at the forefront of cancer research.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Synthesis and Biological Evaluation of New 4-(4-(Methylsulfonyl) Phenyl)-6-Phenylpyrimidin-2-Amine Derivatives as Selective Cyclooxygenase (COX-2) Inhibitors.","authors":"Shabnam Farzaneh, Mohammad Saeed Kordi, Mahsa Azami Movahed, Maryam Bayanati, Afshin Zarghi","doi":"10.2174/0118715206380378250709112246","DOIUrl":"https://doi.org/10.2174/0118715206380378250709112246","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Discussion: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Therapeutic Potential of Cisplatin- and Rutin-Loaded Nanoliposomes against Colorectal Cancer Cells.","authors":"Abdulazeez M Al-Mashhadani, Ali Al-Samydai, Ibrahim Al-Deeb, Simone Carradori, Hanan Azzam, Hussein S Janabi, Dana Al Qudah, Walhan Alshaer, M R Mozafari","doi":"10.2174/0118715206388843250709121645","DOIUrl":"https://doi.org/10.2174/0118715206388843250709121645","url":null,"abstract":"<p><strong>Introduction: </strong>Colorectal cancer is an important cause of cancer-related mortality, necessitating innovative therapies to improve efficacy and reduce side effects. This study explores the potential of Cisplatin and Rutin-loaded nanoliposomes (Cis-NLs and Rut-NLs) for anti-colorectal cancer activity.</p><p><strong>Methods: </strong>Cis-NLs and Rut-NLs were prepared using thin-film hydration, achieving encapsulation efficiencies of 95.5% and 62.5%, respectively. Drug release studies revealed controlled profiles, with Cis-NLs showing a complete release (100%) and Rut-NLs reaching 23.48% over 48 hours. Stability assessments demonstrated minimal changes in size, polydispersity index (PDI), and zeta potential over three months. Encapsulation efficiency decreased slightly for Cis-NLs (92.87%) and significantly for Rut-NLs (26.55%). Several tests were performed to evaluate the biological activity of this combination on colorectal cancer cells and HDF cells to check its selectivity.</p><p><strong>Results: </strong>In vitro cytotoxicity studies on HT29 colorectal cancer cells revealed IC50 values of 1.72 μg/mL for free Cisplatin, 2.35 μg/mL for Cis-NLs, >100 μg/mL for free Rutin, and 63.33 μg/mL for Rut-NLs. A combination of Cis-NLs and Rut-NLs reduced the IC50 to 2.2 μg/mL. Selective toxicity evaluation using human dermal fibroblasts showed an IC50 of 79.24 μM for cisplatin, reduced to 63.3 μM in Cis-NLs, with Rut-NLs demonstrating negligible toxicity.</p><p><strong>Discussion: </strong>Wound healing assays confirmed significant inhibition of cell migration, with wound closure reduced from 62.41% in controls to 34.35% in treated groups. Utilizing nanotechnology, liposomal formulations were synthesized to enhance drug delivery and therapeutic synergy.</p><p><strong>Conclusion: </strong>These results highlight the potential of Cisplatin and Rutin-loaded nanoliposomes as a combination therapy for colorectal cancer.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}