Current topics in medicinal chemistry最新文献

{"title":"Research Progress in Chemical Synthesis and Biosynthesis of Bioactive Pyridine Alkaloids.","authors":"Ning Chen, Xinyu Ma, Bing Liu, Ting Zhu, Yuchen Liu, Ting Li","doi":"10.2174/0115680266385839250731040601","DOIUrl":"https://doi.org/10.2174/0115680266385839250731040601","url":null,"abstract":"<p><p>Pyridine alkaloids possess important biological activities and are widely used in fields such as medicine and pesticides. This paper comprehensively reviews the research progress in the chemical synthesis and biosynthesis of pyridine alkaloids. In terms of chemical synthesis, there are diverse synthesis methods for arylpyridine compounds. For example, 2,4,6-triarylpyridine can be synthesized by using iron-organic framework materials or other reagents. The 3-ethylsulfone pyridine compounds with aryltriazole structures can be synthesized through specific reactions. And 2- arylpyridine can also be synthesized in this way. Heterocyclic pyridine compounds can be prepared into their corresponding derivatives through multiple approaches. The synthesis of polysubstituted pyridine adopts reactions such as cycloaddition, Diels-Alder, condensation, cyclization, and aromatization. The synthesis of polypyridine focuses on the construction of new complexes. Other synthesis methods such as ultrasound-assisted synthesis are also introduced. The main biosynthesis pathways include the co-synthesis of polyketide synthase and non-ribosomal peptide synthase, the origin of lysine, the participation of aspartate, and the synthesis of thiopeptide antibiotics. Meanwhile, the biosynthesis pathways of pyridomycin, pyridine pigment compounds in functional red yeast rice, and vitamin B6 were also discussed, which provides a theoretical basis for further research and application of pyridine alkaloids.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834487","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":"Macrophage-Related GBP4 as a Novel Biomarker for Crohn's Disease: Insights from WGCNA, Mendelian Randomization, and Immunohistochemical Validation.","authors":"Heng Shi, Sisi Liu, Qin Peng","doi":"10.2174/0115680266369945250726090801","DOIUrl":"https://doi.org/10.2174/0115680266369945250726090801","url":null,"abstract":"<p><strong>Introduction: </strong>Crohn's disease (CD) is a complex inflammatory bowel disorder with incompletely understood mechanisms. This study aimed to identify novel biomarkers and elucidate macrophage-related pathogenesis in CD.</p><p><strong>Methods: </strong>Using gene expression data (GSE17928522) from the Gene Expression Omnibus (GEO) database, we compared 1135 CD patients with 180 healthy controls to identify altered gene expression profiles. Immune infiltration analysis was conducted to evaluate changes in immune cell subpopulations. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to construct gene co-expression networks and identify macrophage-associated modules. Mendelian randomization was used to validate the causal role of macrophages. For ex vivo validation, immunohistochemical staining of GBP4 protein expression was performed in colonic tissue samples from 6 CD patients (with ileal or colonic lesions). Non-lesional tissues from the same patients served as intra-individual controls to minimize inter-patient variability.</p><p><strong>Results: </strong>Our analysis revealed significant changes in immune cell subpopulations, particularly macrophages, within the CD microenvironment. A macrophage-associated module was identified, with GBP4 emerging as a critical gene. Immunohistochemical staining confirmed differential expression of GBP4 in CD tissue samples compared to controls.</p><p><strong>Discussion: </strong>This multi-modal study establishes GBP4 as a novel macrophage-associated biomarker for CD, supported by causal Mendelian randomization and immunohistochemical validation. The integration of WGCNA and genetic evidence strengthens the role of macrophage dysregulation in CD pathogenesis. Limitations include population bias in genomic data and small validation cohorts, but the consistency across methodologies underscores GBP4's potential as a therapeutic target.</p><p><strong>Conclusion: </strong>Our findings highlight GBP4 as a novel potential biomarker and therapeutic target in CD, providing insights into the immune-mediated mechanisms underlying the disease. These results contribute to a better understanding of CD pathogenesis and may lead to new therapeutic strategies.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798386","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":"Comprehensive Analysis of TSPAN11: A Potential Prognostic and Immunotherapy Biomarker in Colorectal Cancer.","authors":"Pengjun Sun, Dongbing Li, Jiajia Yan","doi":"10.2174/0115680266392910250728013705","DOIUrl":"https://doi.org/10.2174/0115680266392910250728013705","url":null,"abstract":"<p><strong>Introduction: </strong>Colorectal cancer (CRC) remains a significant global health challenge due to its high incidence and mortality rates. The disease's complexity and heterogeneity impede early diagnosis and effective treatment. The study aims to investigate the role of Tetraspanin 11 (TSPAN11) in CRC, exploring its potential as a prognostic biomarker and immunotherapy target through bioinformatics analysis and experimental validation.</p><p><strong>Methods: </strong>Pan-cancer patient data were obtained from The Cancer Genome Atlas (TCGA) and the GSE71187 dataset, including 672 CRC tissues and 51 adjacent normal tissues. Differential expression analysis, Kaplan-Meier survival analysis, gene set enrichment analysis (GSEA), and immune infiltration assessment were performed. TSPAN11 expression was validated in CRC cell lines using quantitative reverse transcription PCR (qRT-PCR).</p><p><strong>Results: </strong>TSPAN11 was significantly downregulated in CRC tissues compared to normal tissues (p < 0.001), with lower expression associated with poorer overall survival (OS; p = 0.011) and disease- specific survival (DSS; p = 0.038). Multivariate analysis identified TSPAN11 as an independent prognostic factor (p = 0.045). TSPAN11 expression was linked to key pathways such as ECM receptor interaction and TGF-β signaling, and correlated with immune infiltration, immune checkpoint genes, tumor mutational burden (TMB), microsatellite instability (MSI), and drug sensitivity.</p><p><strong>Discussion: </strong>The findings suggest that TSPAN11 may influence CRC progression through multiple biological pathways and immune-related mechanisms. Its downregulation is associated with poorer prognosis and immune evasion, highlighting its potential as a biomarker and therapeutic target. However, validation in larger cohorts and elucidation of underlying mechanisms are needed to confirm these results and translate them into clinical practice.</p><p><strong>Conclusion: </strong>TSPAN11 may serve as a promising prognostic biomarker and immunotherapy target in CRC. Its associations with clinical outcomes, immune features, and drug sensitivity underscore its potential for improving CRC diagnosis and treatment strategies.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798385","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":"Natural Oil and Polycystic Ovary Syndrome: A Comprehensive Review of Therapeutic Benefits.","authors":"Punam Kumari, Pervej Alom Barbhuiya, Ireenia Warjri, Manash Pratim Pathak","doi":"10.2174/0115680266370871250726131232","DOIUrl":"https://doi.org/10.2174/0115680266370871250726131232","url":null,"abstract":"<p><strong>Introduction: </strong>Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting 70-75% of women. This condition is frequently linked with large and dysfunctional ovaries, high levels of androgens, and insulin resistance. A variety of conventional treatments, including metformin, oral contraceptives, and anti-androgen agents, have been used to treat PCOS and its complications, but they have been linked to several negative side effects, including hyperkalemia, weight gain, cardiovascular and hepatic toxicity, vitamin B12 and folic acid deficiency. As a result, there is growing interest in natural methods as complementary or alternative approaches to mitigate these side effects. According to several studies, traditionally used Natural oils (NOs) from various sources have been utilized to identify their ameliorating characteristics against PCOS. The paper aims to study pre-clinical investigations and clinical studies of NOs from different sources against PCOS and gives a comprehensive overview of controlling PCOS. Also, it highlights and tabulates the prominent bioactive phytoconstituents from the reported NOs and their mechanism of action.</p><p><strong>Methods: </strong>For this review purpose, the authors have gone through a vast number of scientific literature from different scientific databases like Google Scholar, ScienceDirect, Web of Science, and PubMed.</p><p><strong>Result: </strong>Mentha spicata L., Foeniculum vulgare Mill., Linum usitatissimum L., Nigella sativa L., Bambusa bambos (L.) Voss, Thuja occidentalis L., Syzygium aromaticum L., Pimpinella anisum L., Rosa canina L., Cocos nucifera L., Oenothera biennis L., Corylus avellana L., and fish oil have been reported to have anti-PCOS activity by maintaining body weight, testosterone, LH, FSH levels, and improving ovarian cysts.</p><p><strong>Discussion: </strong>NOs derived from plant and animal sources show promise in treating PCOS by balancing hormone levels, enhancing ovarian morphology, and alleviating metabolic symptoms. However, significant clinical trials and molecular research are required to evaluate their therapeutic potential, identify suitable dosages, investigate their precise mechanisms of action, and ensure long-term safety and efficacy in PCOS management.</p><p><strong>Conclusion: </strong>Further research is needed to understand the molecular mechanisms of NOs responsible for anti-PCOS activity. Studies are needed to concentrate on their mechanisms of action, routes of impact, safe dosage, and potential side effects to ensure their efficacy and safety in treating PCOS.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793694","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 Review on Discovery, Development, the Chemistry of Quinolones, and Their Antimicrobial Resistance.","authors":"Gayatri S Patil, Kiran N Gaikwad, Shailendra S Suryawanshi, Parixit Bhandurge","doi":"10.2174/0115680266355989250730072511","DOIUrl":"https://doi.org/10.2174/0115680266355989250730072511","url":null,"abstract":"<p><p>Quinolones, discovered in the 1970s, have played a critical role in revolutionizing the treatment of bacterial infections due to their broad-spectrum antimicrobial activity. Over the decades, these compounds have been extensively studied, resulting in the development of numerous new derivatives. This review explores the history and development of quinolones, focusing on their Structure-Activity Relationship (SAR), mechanisms of action, and the challenges posed by antimicrobial resistance. The key resistance mechanisms include mutations in DNA gyrase and topoisomerase IV, which reduce drug binding, plasma-mediated mechanisms, and chromosomal changes that decrease drug uptake or retention. These mechanisms highlight the need for innovative approaches to design quinolones to overcome these resistance pathways. This review also provides an understanding of the SAR of quinolones and, by integrating historical advancements and current challenges, it provides a foundation for the development of next-generation quinolone derivatives with improved efficacy and minimized resistance.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793692","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":"Research Progress on the Mechanisms of Traditional Chinese Medicine in Preventing and Treating HCC Invasion and Metastasis Based on Lipid Metabolic Reprogramming.","authors":"Mengke Wang, Hanning Lyu, Yuxin Liu, Yang Sun","doi":"10.2174/0115680266366687250730060318","DOIUrl":"https://doi.org/10.2174/0115680266366687250730060318","url":null,"abstract":"<p><p>Hepatocellular Carcinoma (HCC) represents a common malignant tumor worldwide, having a profound effect on human health. The processes of invasion and spreading to distant sites are critical malignant biological behaviors exhibited by tumors. The metabolic environment is intricately linked to the initiation, invasion, and subsequent dissemination of tumor cells, with a particular emphasis on lipid metabolism. Lipid metabolism plays a vital role in mediating membrane structure, providing energy, and facilitating signal transduction. It not only delivers energy sources for tumor cells but also establishes conditions conducive to the initiation, progression, and spread of HCC. To meet their energy demands, tumor cells undergo a process of lipid metabolic reprogramming, characterized here as abnormal lipid metabolism. Therefore, a comprehensive investigation into the mechanisms underpinning lipid metabolic reprogramming and its influence on HCC growth and dissemination is crucial for the prevention, early detection, and identification of novel therapeutic targets for HCC. This article initially delineates the metabolic pathways of fatty acids within cells during the development and progression of HCC. It then reviews recent advancements in understanding abnormal lipid metabolism, focusing on the associated genes, enzymes, proteins, and metabolic products that promote HCC progression and spread. Furthermore, a brief overview of the Tumor Immune Microenvironment (TIME) in HCC is provided, highlighting the interactions between Tumor-Associated Macrophages (TAMs) and HCC lipid metabolic reprogramming, as well as their effects on HCC growth and dissemination. Lastly, it examines the treatments targeting abnormal lipid metabolism in HCC utilizing Traditional Chinese Medicine (TCM) and natural products, offering new perspectives for targeting HCC lipid metabolic reprogramming to inhibit spread and invasion.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793695","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":"Elucidating the Role of Galectin-3 in the Recurrence of Primary Sclerosing Cholangitis Post-Liver Transplantation as a Potential Therapeutic Target.","authors":"Rozita Khodashahi, Asieh Hatefi Olaee, Gordon A Ferns, Mohsen Aliakbarian, Mohammad-Hassan Arjmand","doi":"10.2174/0115680266378899250630063559","DOIUrl":"https://doi.org/10.2174/0115680266378899250630063559","url":null,"abstract":"<p><p>Primary sclerosing cholangitis (PSC) occurs in approximately 25% of patients post-liver transplantation (LT) and is associated with significant morbidity and mortality. Hepatic duct cholestasis following recurrent PSC may lead to the development of liver cirrhosis and the need for liver retransplantation. To date, the exact etiology of the recurrence of PSC post-LT remains unknown, and it is not currently possible to predict which patients are at risk for recurrence of PSC. Extracellular Galectin-3 (Gal-3) acts as a damage-associated molecular pattern (DAMP) when released into the extracellular matrix (ECM) by injured liver cells. Gal-3 plays a crucial role in immune responses and inflammation by binding and cross-linking surface proteins of neutrophils and macrophages, facilitating the chemotaxis of immune cells to the site of injury, and activating the macrophage inflammasome complex. In addition, Gal-3, by activation of hepatic satellite cells (HSC) to myofibroblast phenotype, induces profibrotic molecules, such as transforming growth factor beta (TGF-β) and increases the expression of collagens in the ECM, leading to liver fibrogenesis. According to the evidence, targeting Gal-3 may have important therapeutic potential in preventing the progression of recurrence in PSC and cholestatic progression post-LT.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793693","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":"Total Synthesis of Biologically Potent Peptides and their In Silico Studies: A TAG Approach.","authors":"Ramya M, Veeranjaneyulu Avula, Kiran Kumar B, Nagendra G","doi":"10.2174/0115680266377804250721145504","DOIUrl":"https://doi.org/10.2174/0115680266377804250721145504","url":null,"abstract":"<p><strong>Introduction: </strong>Current trends in peptide synthesis protocols have emerged as the most attractive domain in the field of pharma and medicine. Since most of the peptide/peptidomimeticbased molecules serve as potential candidates for many diseases, as they are bioavailable molecules.</p><p><strong>Methods: </strong>We present the synthesis of bioactive peptides through TAGGING approach with the help of TAG-OH as a linker to the Nα-protected amino acid.</p><p><strong>Results: </strong>FRDEHKK and NKDRG are two peptides that possess antioxidant and antiproliferative activity, and their in-silico investigations reveal that they exhibit anticancer properties when bound to the AXL kinase and EGFR proteins.</p><p><strong>Discussion: </strong>This TAG method enables the easy isolation of peptides at each step as solids, and all the impurities were washed off by simple filtration. The method allows a bulk-scale preparation of the peptides without any difficulty, and hence the protocol is highly efficient for the production of peptides of therapeutic importance.</p><p><strong>Conclusion: </strong>The two peptides FRDEHKK and NKDRG were isolated as fine solids with 82% and 85% yield and were characterized by NMR and MASS spectroscopy. In-silico studies reveal FRDEHKK and NKDRG peptides exhibit good affinity towards EGFR and AXL kinase.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788518","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":"Pharmaceutical Sciences Encompass A Wide Range of Techniques and Methodologies.","authors":"Uma Agarwal, Swati Paliwal, Rajiv Kumar Tonk","doi":"10.2174/0115680266397266250725101317","DOIUrl":"https://doi.org/10.2174/0115680266397266250725101317","url":null,"abstract":"<p><p>Pharmaceutical research and development encompass a series of interconnected steps that are crucial for creating safe and effective drug candidates targeting specific diseases. This process involves rigorous testing and evaluation to ensure that the drugs developed meet safety standards and therapeutic efficacy. The significance of this systematic approach lies in its ability to address the complications of various diseases, ultimately leading to advancements in medical treatment and patient care. The successful development of a drug candidate is contingent upon thorough research, which includes preclinical studies and clinical trials, ensuring that the final product is both reliable and beneficial for patients. The review emphasizes the importance of a systematic approach in the pharmaceutical research and development sector. It highlights the interconnected steps necessary for the successful development of drugs, underscoring the critical need for safety and efficacy in pharmaceutical products. The primary objective is to ensure that the drugs developed meet the standards required for public use, thereby enhancing public health outcomes. Overall, the review serves as a guide for stakeholders in the pharmaceutical industry to prioritize safety and effectiveness throughout the drug development process. With an emphasis on the interrelated processes in the drug development process and the significance of new and advanced approaches, this article highlights the evidence based on the importance of a systematic and structured approach in drug development. It points out that a systematic approach is crucial in pharmaceutical Research and Development (R&D) to ensure successful outcomes. It is essential to continuously update and understand these steps to keep pace with advancements in the field. Additionally, staying informed about the development of new and advanced techniques at each stage of drug R&D is vital for enhancing efficiency and effectiveness. This comprehensive literature review was conducted using databases such as PubMed and Scopus, focusing on research published up to January 2025. Continuous upgrades in awareness about R&D and innovative procedures within the industry are essential. It highlights the importance of following systematic methods to ensure that R&D practices remain relevant and practical. Moreover, this understanding is necessary for the safe and effective creation of pharmaceuticals. Ultimately, enhancing this awareness is likely to improve the overall effectiveness of R&D processes.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783718","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":"Preliminary Study on GZMA- and GSDMB-Associated Pyroptosis and CD8+ T Cell-Mediated Immune Evasion in Skin Cutaneous Melanoma.","authors":"Jianqin Chen, Zhirong Huang, Fengfeng Xie, Jing Liu, Wen Sun, Jingli Xu, Wenfang Xie","doi":"10.2174/0115680266416033250731102049","DOIUrl":"https://doi.org/10.2174/0115680266416033250731102049","url":null,"abstract":"<p><strong>Background: </strong>Skin cutaneous melanoma (SKCM) is a life-threatening malignancy, and pyroptosis-mediated inflammatory response is associated with SKCM progression. We aimed to uncover the underlying pathogenesis of SKCM based on pyroptosis features.</p><p><strong>Method: </strong>The single-cell and bulk RNA-seq data and clinical information of SKCM patients were downloaded from the TCGA and GEO databases, and the REACTOME_ PYROPTOSIS.v2024.1.Hs.gmt from the MSigDB database was used for Gene Set Enrichment Analysis (GSEA). Differentially expressed gene (DEG) analysis was performed utilizing the \"limma\" R package, and the \"GSVA\" R package was used for the analysis of pyroptosis pathway activation. In addition, scRNA-seq analysis and cell communication analysis were carried out by employing the \"Seurat\" R package and \"CellChat\" R package, respectively. Gene expression was measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR), while cell counting kit-8 (CCK-8), wound healing, and Transwell assays were carried out to assess cell proliferation, migration, and invasion, respectively.</p><p><strong>Results: </strong>DEGs analysis detected no significant pyroptosis-related DEGs. Analysis of the expression of two representative pyroptosis genes (GZMA and GSDMB) revealed that GZMA was significantly upregulated in the SKCM tissues, but the expression of GSDMB was downregulated. The pyroptosis pathway was not activated in the tumor group. In addition, we observed that high expression of GZMA and GSDMB was closely associated with a favorable outcome in SKCM. The two genes were downregulated in SKCM cells, while the overexpression of GZMA significantly impaired the proliferation, migration, and invasion ability of SKCM cells. Nine main cell subpopulations were identified, and GZMA was specifically overexpressed in CD8+ T cells. Gene function analysis revealed that specific genes of CD8+ T cells were enriched in cell death-related and inflammation activation pathways. Cell communication demonstrated that CD8+ T cells interacted with melanocytes through the CD99-CD99 and HLA-C-KIR2DL3 ligand-receptor pairs.</p><p><strong>Conclusion: </strong>Based on the pyroptosis features in SKCM, this study found that blocking GZMA proteins in CD8+ T cells within melanocytes may be the underlying pathogenesis for tumor immune escape in cancer.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774875","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}