Anti-cancer agents in medicinal chemistry最新文献

{"title":"CD98 Light Chain LAT1 Tracers in PET-CT Diagnosis of Cancer Patients.","authors":"Pu Xia","doi":"10.2174/0118715206381956250622145301","DOIUrl":"https://doi.org/10.2174/0118715206381956250622145301","url":null,"abstract":"<p><p>Amino acid-based PET tracers have become vital tools for non-invasive tumor imaging, offering greater specificity and sensitivity than conventional 18F-FDG. These tracers target amino acid transporters, particularly L-type Amino Acid Transporter 1 (LAT1), which is overexpressed in rapidly proliferating tumor cells. Various 18F-labeled amino acid tracers have been explored for imaging different malignancies, including gliomas, neuroendocrine tumors, and lung cancers. This review summarizes the performance of LAT1-specific radiotracers, comparing their uptake ratios, sensitivity, and specificity in cancer diagnosis. These tracers have led to significant advancements in tumor imaging, providing better diagnostic accuracy, enhanced tumor delineation, and reduced interference from inflammatory tissue. Although promising, the clinical utility of these tracers requires further research and clinical trials to refine their applications and optimize their role in routine clinical practice. Continued development will be crucial in making these tracers more effective and widely applicable for cancer diagnosis and treatment planning.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558886","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":"Secondary Malignancies of Chimeric Antigen Receptor T-cell Therapy: A Multidimensional Analysis of Mechanisms, Risk Factors, and Treatment Strategies.","authors":"Ye Kang, Da-Sheng Dang, Xue Sun, Xiao Zhang","doi":"10.2174/0118715206378956250618182616","DOIUrl":"https://doi.org/10.2174/0118715206378956250618182616","url":null,"abstract":"<p><p>Chimeric Antigen Receptor T-cell (CAR-T) therapy represents a pioneering advancement in immunotherapy, demonstrating substantial clinical success in the treatment of hematologic malignancies, particularly in B-cell hematologic malignancies. This therapeutic approach involves the genetic modification of a patient's Tcells to express receptors specific to tumor antigens, thereby enabling the CAR T-cells to identify and eradicate tumor cells, which significantly enhances the patient's treatment prognosis. Despite the remarkable efficacy of CAR-T therapy, concerns regarding its safety have emerged during clinical implementation. Notably, research has indicated that CAR T-cell therapy may be associated with the development of secondary primary malignancies, prompting considerable apprehension within the clinical community regarding the long-term adverse effects of this treatment modality. This article aims to investigate the potential mechanisms responsible for the induction of secondary primary malignancies by CAR T-cells, evaluate the associated risk factors, and discuss therapeutic strategies to mitigate this issue. Furthermore, the article will explore future research directions focused on optimizing the safety profile of CAR-T therapy, thereby providing a theoretical foundation for the development of safer and more effective therapeutic interventions.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526171","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":"Screening of Bioactive Fractions from Balanites aegyptiaca and Pterocarpus Marsupium for Anticancer Effects in HepG2 and U87MG Cels.","authors":"Divya Vashishth, Mansi Yadav, Ajay Kumar, Gulshan Rohilla, Minakshi Vashist, Sudhir Kumar Kataria","doi":"10.2174/0118715206396025250614030603","DOIUrl":"https://doi.org/10.2174/0118715206396025250614030603","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer is a group of diseases caused by uncontrollable cell growth. Herbal medicines, derived from plants, have been used for centuries across cultures for their therapeutic benefits, effectively treating conditions like cancer. This study represents the anticancer effects of fractions of some medicinal plant extracts along with their apoptotic studies and their induction through p53-mediated Bax and Bcl-2 mRNA expression in HepG2 and U87MG cells.</p><p><strong>Methods: </strong>The fractionation of crude methanolic extracts was done using Column Chromatography and Thin Layer Chromatography. The fractions were analysed for cytotoxicity against both the cell lines by MTT assay. Cancer cells were treated with 2 most active fractions and their mechanism of apoptosis induction was assessed by Flow Cytometry studies and the mRNA expression levels of p53, Bax, and Bcl-2 were determined by Reverse Transcriptase PCR. The presence of phytoconstituents in the active fractions was analysed by GC-MS.</p><p><strong>Results: </strong>The active fractions revealed the apoptosis induction in both the cell lines and the RT-PCR studies suggested the mechanism of apoptosis induction through upregulation of p53 and Bax and downregulation of Bcl-2 mRNA. The GC-MS analysis of active fractions from Balanites aegyptiaca and Pterocarpus marsupium revealed the presence of phytochemicals such as 4-O-Methylmannose, Oleic acid, Erucic acid, etc. which might have contributed to the anti-proliferative and apoptotic effects of these fractions.</p><p><strong>Discussion: </strong>4-O-Methylmannose was the major component identified with the highest peak area of 59%. The fractions from all the 4 plant extracts demonstrated significant cytotoxic effects on the liver (HepG2) and brain (U87MG) cancer cell lines, with particular emphasis on the active fractions BA FII, PM FII, and PM FIII. Additionally, the mechanisms of apoptosis induction through the modulation of p53, Bax, and Bcl-2 pathways, along with the presence of bioactive compounds further support the anticancer efficacy of these plant extracts. Also, to the best of our knowledge, this is the first study on fractions of Balanites aegyptiaca and Pterocarpus marsupium against U87MG cells.</p><p><strong>Conclusion: </strong>The results highlight the promising potential of plant-derived natural products as anticancer agents. These findings provide valuable insight into the potential of herbal medicines and encourage further exploration of plant-based therapies for cancer treatment.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537811","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":"Unveiling the Vital Role of ACTA2-AS1 in Human Cancers: Molecular Mechanisms and Clinical Applications.","authors":"Haodong He, Lumei Xiang, Baoqin Pi, Jingjie Yang, Wenjin Peng, Moyu Li, Haoran Liu, Xinyan Zheng, Haoyi Liu, Yuxiang Peng, Pengbo Zhang, Jiahe Zhang, Xin Chen, Yanlin Zhang, Meiyan Shuai, Feng Xu, Yan Cai, Chengfu Yuan","doi":"10.2174/0118715206381499250607114710","DOIUrl":"https://doi.org/10.2174/0118715206381499250607114710","url":null,"abstract":"<p><strong>Background: </strong>The smooth muscle α‑actin 2‑antisense 1 (ACTA2-AS1), also known as ZXF1, is an emerging cancer-associated long non-coding RNA (lncRNA) that has garnered significant attention in recent years. ACTA2-AS1 is situated on human chromosome 10 at location 10q23.31, comprising five exons and a single transcript. The aberrant expression of ACTA2-AS1 has been noted in 10 malignant tumors, correlating significantly with unfavorable clinicopathological characteristics and poor patient prognosis.</p><p><strong>Objective: </strong>This review encapsulates recent progress in ACTA2-AS1 research, examining its expression profile, biological functions, molecular mechanisms, and anticipated influence on cancer diagnosis, treatment, and prognosis, emphasizing its potential as a novel therapeutic target based on lncRNA and its prognostic utility as a biomarker.</p><p><strong>Methods: </strong>Based on a comprehensive search of the PubMed database for the biological function of lncRNA ACTA2-AS1 in malignant tumors, the current research is systematically summarized and critically analyzed.</p><p><strong>Results: </strong>ACTA2-AS1 plays a complex role in various biological processes in tumor cells, encompassing proliferation, apoptosis, and cell cycle arrest. It also contributes to migration, invasion, epithelial-mesenchymal transition (EMT), and drug resistance. Mechanistically, ACTA2-AS1 influences oncogenic or tumor-suppressive effects via a complex regulatory network. It can adsorb specific 5 miRNAs as competitive endogenous RNAs (ceRNAs), thereby mitigating the suppression of downstream mRNA targets implicated in tumorigenesis (e.g., SOX7, KLF9, CXCL2, BCL2L11, etc.) and modulating their downstream signaling pathways (e.g., Wnt5a/PKC, SMAD3, mTOR, etc.), demonstrating a broad spectrum of dual roles in carcinogenesis and tumor suppression.</p><p><strong>Conclusion: </strong>ACTA2-AS1 is a promising biomarker and molecular target for the treatment of cancer.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473758","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":"Advances in Metal-based Nanotechnology-based Optical Therapy for the Targeted Treatment of Colorectal Cancer.","authors":"Huiling Zuo, Yuhang Jiao, Fengyu Wang, Junzi Wu, Wenling Chen","doi":"10.2174/0118715206378631250611101427","DOIUrl":"https://doi.org/10.2174/0118715206378631250611101427","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is one of the most prevalent gastrointestinal malignancies in the world. To overcome clinical challenges, such as high postoperative recurrence rates and prominent resistance to chemotherapy, new therapeutic strategies are urgently needed. Phototherapy, particularly Photodynamic Therapy (PDT) and Photothermal Therapy (PTT), has unique advantages in selectively killing tumor cells. However, traditional Photosensitizers (PSs) and Photothermal Agents (PTAs) have inherent defects, such as limited tissue penetration depth, poor optical stability, and insufficient targeting ability, which severely restrict phototherapy in clinical applications. Significant advancements have been made in enhancing the phototherapeutic effects of metal nanomaterials in recent years. This progress can be attributed to their tunable optical properties, exceptional Photothermal Conversion Efficiency (PCE), and unique Surface Plasmon Resonance (SPR) effects. In this review, we systematically summarized the latest progress in research on the use of metal nanomaterials for the optical diagnosis and treatment of colorectal cancer. We focused on the mechanism by which typical nanomaterials such as gold, silver, and platinum enhance the therapeutic effect of PDT/PTT. Additionally, a comprehensive analysis was conducted to evaluate the application and potential of nano-optical sensitizers incorporating metallic cores such as gold, silver, iridium, platinum, iron, zinc, copper, ruthenium, and titanium for the diagnosis and treatment of Colorectal Cancer (CRC). This review may provide theoretical guidance for developing new-generation optical diagnostic and therapeutic strategies for treating colorectal cancer.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473756","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":"Exploring Natural Coumarins: Breakthroughs in Anticancer Therapeutics.","authors":"Emine Terzi, Beyza Ecem Oz-Bedir, Jean Yves Winum","doi":"10.2174/0118715206385367250610045200","DOIUrl":"https://doi.org/10.2174/0118715206385367250610045200","url":null,"abstract":"<p><p>Natural coumarins, a class of compounds found abundantly in various plants, are emerging as promising candidates in fight against cancer. Their ability to target multiple cancer-related processes has drawn significant interest from researchers. Natural coumarins exhibit anticancer effects through mechanisms such as inducing apoptosis, which is the programmed death of cancer cells, inhibiting cell proliferation, and disrupting angiogenesis, the process by which tumors develop their own blood supply to sustain growth. What makes coumarins particularly intriguing is their broad-spectrum activity against various types of cancer cells, from breast to lung to colon cancers. They interact with key molecular pathways that drive tumor progression, making them versatile agents in cancer therapy. Additionally, unlike many conventional chemotherapy drugs, natural coumarins generally have lower toxicity, which could translate to fewer side effects for patients. This characteristic makes them attractive as potential standalone treatments or as complementary therapies that enhance the efficacy of existing drugs while minimizing harm to normal cells. Ongoing research continues to explore the therapeutic potential of natural coumarins to better understand their full therapeutic potential and how they might work in combination with other anticancer agents. As the body of evidence grows, these natural compounds could become integral components of more effective and less harmful cancer treatment regimens, offering new hope for patients facing this challenging disease. This review was conducted by systematically analyzing the existing literature on natural coumarins and their anticancer potential.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473757","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":"Determination of PD-L1 Expression in Circulating Tumor Cells of Hypopharyngeal and Laryngeal Cancers and Correlation with Tissue Detection.","authors":"Chen Li, Hongyu Zhu, Qin Lin, Wei Chen, Xiaoting Huang, Desheng Wang","doi":"10.2174/0118715206340244250605061005","DOIUrl":"https://doi.org/10.2174/0118715206340244250605061005","url":null,"abstract":"<p><strong>Background: </strong>PD-L1 plays a pivotal role as an immunoregulatory checkpoint within the immune system, exerting a critical influence on the internal functioning and survival mechanisms of cancer cells. This study aimed to elucidate the clinical significance of PD-L1 expression in Circulating Tumor Cells (CTCs) derived from individuals afflicted with Hypopharyngeal and Laryngeal Cancers (HLC), as well as its potential implications for clinical practice.</p><p><strong>Objective: </strong>The aim of this study was to verify the relationship between the expression of PD-L1 in CTCs in HLC and the consistency in tissue and the preliminary clinical application.</p><p><strong>Methods: </strong>A laboratory-based experimental study was carried out at Fujian Medical University Union Hospital. CTCs were identified using an immunomagnetic positive sorting methodology. Simultaneous detection was conducted on the CTC levels among PD-L1 positive patients, aiming to ascertain the dynamic relationship between real-time CTC fluctuations and the clinicopathological indices of the patients. This investigation encompassed a cohort of 38 individuals, wherein PD-L1 expression analysis was executed to delineate CTC variations in PD-L1- positive patients.</p><p><strong>Results: </strong>The constructed immunolipid magnetic nano-beads demonstrated pronounced efficacy in capturing CTCs, and the lipid nanoparticles exhibited noteworthy capture efficiency coupled with minimal cytotoxic effects. The assessment of PD-L1 expression consistency between CTCs and tissue specimens revealed a substantial agreement surpassing 70%. Furthermore, inhibition of PD-L1 yielded a significant elevation in the cytokine TNF- α levels, accompanied by a concomitant reduction in IL-10 levels.</p><p><strong>Conclusion: </strong>The CTC sorting system devised in this investigation boasts attributes of remarkable specificity and sensitivity. By virtue of PD-L1 expression analysis, it holds the potential to offer instructive implications for tailoring individualized treatments in clinical scenarios.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282033","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":"HSP Inhibitor Sensitize Resistant MCF-7 Cells to Doxorubicin through Suppressing HSP90AB4P Pseudogene and HSPB1 Expression.","authors":"Kubra Acikalin Coskun, Lütfi Tutar, Elif Cansu Abay, Levent Gülüm, Ayşe Büşranur Çelik, Mehmet Gumus, İrfan Koca, Yusuf Tutar","doi":"10.2174/0118715206374072250530103333","DOIUrl":"https://doi.org/10.2174/0118715206374072250530103333","url":null,"abstract":"<p><strong>Introduction: </strong>Doxorubicin, a first-line chemotherapeutic agent, often faces resistance in breast cancer subtypes, leading to treatment failure. HSPs (Heat shock proteins), especially HSP90, and their pseudogenes like HSP90AB4P have been implicated in fostering resistance mechanisms by regulating apoptotic and survival pathways in cancer cells. The aim of this study is to investigate how inhibiting HSPs using a novel pyro-salicylic acid derivative (7A) can sensitize doxorubicin-resistant breast cancer cells (MCF-7/ADR) to chemotherapy.</p><p><strong>Methods: </strong>The potential role of HSP inhibitor with doxorubicin at different concentrations was tested to reveal synergetic and additive effects by combination index (CI) analysis. Cell cycle analysis, apoptosis assays, and gene expression profiling via PCR arrays supported the impact of 7A over MCF-7/ADR cells' molecular pathways.</p><p><strong>Results: </strong>HSP inhibitor efficiently suppressed doxorubicin resistance over invasive breast ductal carcinoma and has a synergetic effect. The inhibitor decreases HSP90AB4P and small HSPB1 expression efficiently.</p><p><strong>Conclusion: </strong>Our findings demonstrate that 7A suppresses doxorubicin resistance in MCF-7/ADR cells by reducing the expression of HSP90AB4P and small HSPB1, leading to an increase in apoptosis and cell cycle arrest. The combination of 7A and doxorubicin exhibits a synergistic effect (CI < 1), enhancing cytotoxicity and overcoming resistance mechanisms. The cells are driven to apoptosis and the inhibitor significantly decreases doxorubicin resistance. Targeting HSPB1 and its pseudogene HSP90AB4P with 7A offers a promising therapeutic strategy to overcome doxorubicin resistance in breast cancer.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282035","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":"Exploring the Therapeutic Potential of Ocimum sanctum and Phanera variegata in Breast Cancer Treatment: A Promising Natural Approach.","authors":"Tohfa Siddiqui, Md Nasar Mallick, Vikram Sharma","doi":"10.2174/0118715206375507250603074251","DOIUrl":"https://doi.org/10.2174/0118715206375507250603074251","url":null,"abstract":"<p><p>Breast cancer is one of the most common malignancies affecting women worldwide. It is a complex, heterogeneous disease, classified into several subtypes, including hormone receptor-positive and triple-negative breast cancer (TNBC), each with distinct therapeutic challenges. TNBC, in particular, is characterized by its aggressive nature and lack of targeted therapies due to the absence of estrogen, progesterone, and HER2 receptors. This review explores the potential of natural plant-based compounds, especially focusing on Clove Basil (Ocimum sanctum) and Phanera variegata, in combating breast cancer. These plants have been traditionally used for their medicinal properties and are now being studied for their anticancer effects. Ocimum sanctum has demonstrated significant antiproliferative and pro-apoptotic effects against breast cancer cells, particularly the MCF-7 line, through mitochondrial pathway activation and gene regulation. Similarly, Phanera variegata exhibits potential through its rich content of flavonoids and other bioactive compounds, which have been shown to induce apoptosis, reduce tumor growth, and offer antioxidant benefits. The review highlights how these plant extracts, with their multiple mechanisms, including immune modulation and direct cytotoxic effects, hold promise as adjunctive or alternative therapies in breast cancer treatment, particularly for hard-to-treat subtypes like TNBC. Continued research into their molecular pathways and therapeutic efficacy could lead to new, less toxic treatment options.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282034","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":"Novel Heterocyclic Compounds Exhibit Potent Antileukemic Activity through Selective Induction of Apoptosis and HDAC8 Interaction in AML Cells.","authors":"Túlio R Freitas, Fernanda de F S de Oliveira, Caique Lopes Duarte, Larissa R S P Baliza, Edward K S Gonçalves, Silmara N de Andrade, Diego P Sangi, Fernando de P Varotti, Adriano de P Sabino","doi":"10.2174/0118715206370289250313062830","DOIUrl":"https://doi.org/10.2174/0118715206370289250313062830","url":null,"abstract":"<p><strong>Introduction: </strong>Heterocyclic compounds serve as the structural framework for many commercially available drugs and are well known for their antitumor properties.</p><p><strong>Aim: </strong>This study aimed to evaluate the cytotoxic effects, apoptosis induction, changes in cell cycle progression, and gene expression alterations of new heterocyclic compounds and their precursors against the acute monocytic leukemia cell line THP-1 through in vitro experimentation and computational approaches.</p><p><strong>Methods: </strong>The study employed cytotoxicity assays, flow cytometry analyses, gene expression evaluations, oral bioavailability studies, and molecular modeling. Among the compounds tested, 6, 25, and 26 demonstrated the greatest potency and selectivity, exhibiting substantially increased cytotoxicity (1.18 μM < IC50 < 7.66 μM) against the THP-1 cell line. Investigations into apoptosis induction and cell cycle changes revealed that these compounds primarily caused an increase in the number of THP-1 cells undergoing apoptosis after 48 hours of treatment. Additionally, compounds 6 and 25 induced an accumulation of cells in the G0/G1 phase in the same cell line.</p><p><strong>Results: </strong>Regarding gene expression, a shift in the expression profile of genes associated with apoptotic mechanisms was observed. Furthermore, in silico analysis revealed that these three active compounds potentially interact with histone deacetylase 8 (HDAC8), a protein known to be associated with cancer.</p><p><strong>Conclusion: </strong>These findings underscore the potential of these compounds as candidates for the development of novel therapeutic approaches in oncology.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257172","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}