Acta Pharmaceutica最新文献_第6页

Exploration of the chemical space of benzamide-based voltage-gated potassium channel K_v1.3 inhibitors. 苯酰胺基电压门控钾通道Kv1.3抑制剂的化学空间探索。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-07-03 Print Date: 2025-06-01 DOI: 10.2478/acph-2025-0019

Marzia Fois, Špela Pelcar, Joshua A Nasburg, Heike Wulff, Lucija Peterlin Mašič, Tihomir Tomašič

{"title":"Exploration of the chemical space of benzamide-based voltage-gated potassium channel Kv1.3 inhibitors.","authors":"Marzia Fois, Špela Pelcar, Joshua A Nasburg, Heike Wulff, Lucija Peterlin Mašič, Tihomir Tomašič","doi":"10.2478/acph-2025-0019","DOIUrl":"10.2478/acph-2025-0019","url":null,"abstract":"The voltage-gated potassium channel Kv1.3 is a key regulator of T-cell activation and a validated therapeutic target for autoimmune and inflammatory diseases. In this study, a ligand-based design strategy was employed to expand a library of benzamide-derived Kv1.3 inhibitors. Starting from a previously optimised thiophene-based inhibitor, structu ral modifications were introduced to the 2-methoxybenzamide moiety and the central tetrahydropyran or cyclohexane scaffold. A series of ketone, hydroxy, and carbamate derivatives was synthesised and evaluated for Kv1.3 inhibition using whole-cell patch-clamp electrophysiology. Structure-activity relationship analysis revealed that cis-isomers in the hydroxy series exhibited stronger activity than their trans counterparts, with some analogues displaying submicro-molar IC 50 values. In the carbamate series, trans-isomers were generally more potent, with trans-18 and trans-16 achieving IC 50 values of 122 and 166 nmol L-1, respectively. These results provide valuable insights into the design of Kv1.3 inhibitors and support further development of these compounds for immunomodulatory applications.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"75 2","pages":"219-233"},"PeriodicalIF":2.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558756","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}

引用次数: 0

Design, synthesis, and evaluation of a novel fluorescent probe for competitive fluorescence polarization assay to screen galectin-8 inhibitors. 一种新型荧光探针的设计、合成和评价，用于竞争性荧光偏振法筛选半乳糖凝集素-8抑制剂。

IF 1.4 4区医学

Acta Pharmaceutica Pub Date : 2025-07-03 Print Date: 2025-06-01 DOI: 10.2478/acph-2025-0010

Edvin Purić, Marina Marinović, Zala Kojek, Barbro Kahl-Knutson, Hakon Leffler, Ulf J Nilsson, Marko Anderluh, Janez Mravljak

引用次数: 0

Optimization of 6-(trifluoromethyl)pyrimidine derivatives as TLR8 antagonists. 6-（三氟甲基）嘧啶衍生物TLR8拮抗剂的优化。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-07-03 Print Date: 2025-06-01 DOI: 10.2478/acph-2025-0011

Nika Strašek Benedik, Valerij Talagayev, Troy Matziol, Ana Dolšak, Izidor Sosič, Günther Weindl, Gerhard Wolber, Matej Sova

{"title":"Optimization of 6-(trifluoromethyl)pyrimidine derivatives as TLR8 antagonists.","authors":"Nika Strašek Benedik, Valerij Talagayev, Troy Matziol, Ana Dolšak, Izidor Sosič, Günther Weindl, Gerhard Wolber, Matej Sova","doi":"10.2478/acph-2025-0011","DOIUrl":"10.2478/acph-2025-0011","url":null,"abstract":"Toll-like receptors (TLRs) are essential for the innate immune system as they recognize pathogen-associated molecular patterns and trigger immune responses. Overactivation of TLR8 by endogenous nucleic acids is associated with the development of autoimmune diseases and promotes inflammatory responses. This study presents the design, synthesis, and evaluation of a series of TLR8 antagonists based on the optimization of previously reported 6-(trifluoromethyl)pyrimidin-2-amines, with targeted modifications to further explore structure-activity relationships (SAR) and increase potency. A two-step synthesis involving nucleophilic aromatic substitution and Suzuki coupling was used to prepare two series of new compounds. The biological evaluation revealed that compounds 14 and 26 exhibited promising TLR8 antagonistic activity with IC 50 values of 6.5 and 8.7 μmol L- 1, respectively. Compound 14 showed reduced cell viability at higher concentrations, while compound 26 showed no cytotoxic effects, making it a promising candidate for further investigation.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":"159-183"},"PeriodicalIF":2.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959648","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}

引用次数: 0

Development and evaluation of novel InhA inhibitors inspired by thiadiazole and tetrahydropyran series of inhibitors. 以噻二唑和四氢吡喃系列抑制剂为灵感的新型InhA抑制剂的开发和评价。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-07-03 Print Date: 2025-06-01 DOI: 10.2478/acph-2025-0016

Martina Hrast Rambaher, Nina Gradišek, Rok Frlan, Izidor Sosič, Aljoša Bolje, Jakob Kljun, Martin Juhás, Stanislav Gobec, Stane Pajk

{"title":"Development and evaluation of novel InhA inhibitors inspired by thiadiazole and tetrahydropyran series of inhibitors.","authors":"Martina Hrast Rambaher, Nina Gradišek, Rok Frlan, Izidor Sosič, Aljoša Bolje, Jakob Kljun, Martin Juhás, Stanislav Gobec, Stane Pajk","doi":"10.2478/acph-2025-0016","DOIUrl":"10.2478/acph-2025-0016","url":null,"abstract":"Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a leading global health challenge, exacerbated by the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. One promising therapeutic target is the enzyme enoyl-acyl carrier protein reductase (InhA), which plays a vital role in the biosynthesis of mycolic acids, essential components of the bacterial cell wall. Direct inhibition of InhA offers a potential strategy for overcoming resistance mechanisms, particularly in cases where the activation of conventional drugs like isoniazid is compromised. This study investigates two novel series of InhA inhibitors based on thiadiazole and tetrahydropyran lead compounds, originally identified through high-throughput screening by GSK. Analogues were synthesised using the copper-catalysed azide-alkyne cycloaddition (CuAAC) click reaction, and their inhibitory activity was tested against InhA. Among the tested compounds, only one exhibited modest inhibitory activity, with an IC 50 of 11 µmol L-1, while others were inactive. Interestingly, during the synthetic efforts, a novel reaction was discovered between aryl methyl ketones and ethynylmagnesium bromide, yielding 1,3-diols, as confirmed by X-ray diffraction analysis. These findings underscore the challenges of optimising InhA inhibitors and highlight the potential of synthetic innovations in exploring new synthetic pathways.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"75 2","pages":"185-218"},"PeriodicalIF":2.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558755","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}

引用次数: 0

Impact of peroxide content in excipients and antioxidants on famotidine oxidative stability. 赋形剂和抗氧化剂中过氧化物含量对法莫替丁氧化稳定性的影响。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-07-03 Print Date: 2025-06-01 DOI: 10.2478/acph-2025-0020

Alen Gabrič, Žiga Hodnik, Janez Ilaš, Stane Pajk

{"title":"Impact of peroxide content in excipients and antioxidants on famotidine oxidative stability.","authors":"Alen Gabrič, Žiga Hodnik, Janez Ilaš, Stane Pajk","doi":"10.2478/acph-2025-0020","DOIUrl":"10.2478/acph-2025-0020","url":null,"abstract":"Famotidine, a widely used H2-receptor antagonist, exhibits sensitivity to oxidative degradation, particularly in the presence of excipients containing peroxide impurities. This study explores the oxidative stability of famotidine under various storage conditions, with a specific focus on excipients with varying peroxide contents. A stability-indicating liquid chromatography-mass spectrometry (LC-MS) method was developed to identify and quantify famotidine degradation products, providing detailed insights into oxidative pathways. In addition, Zeneth software was employed to predict potential degradation products, and its predictive accuracy was evaluated against experimental findings. Antioxidants, including ascorbic acid, propyl gallate, and ethylenediaminetetraacetic acid (EDTA), were incorporated into compressed compatibility mixtures to assess their effects on peroxide-mediated degradation. While propyl gallate and EDTA consistently reduced peroxide levels and enhanced stability, ascorbic acid unexpectedly acted as a pro-oxidant under stress conditions, accelerating peroxide formation in povidone. These findings provide critical insights into mitigating oxidative degradation in famotidine and other solid dosage forms, emphasizing the importance of selecting appropriate excipients, antioxidants, and predictive tools to ensure product stability.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"75 2","pages":"259-272"},"PeriodicalIF":2.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558757","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}

引用次数: 0

FOXD2-AS1 is modulated by METTL3 with the assistance of YTHDF1 to affect proliferation and apoptosis in esophageal cancer. METTL3在YTHDF1的辅助下调控FOXD2-AS1影响食管癌的增殖和凋亡。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-04-10 Print Date: 2025-03-01 DOI: 10.2478/acph-2025-0009

Zijin Wang, Xing Chen Liu, Zhen Gya Gao, Wo Da Shi, Wen Cai Wang

{"title":"FOXD2-AS1 is modulated by METTL3 with the assistance of YTHDF1 to affect proliferation and apoptosis in esophageal cancer.","authors":"Zijin Wang, Xing Chen Liu, Zhen Gya Gao, Wo Da Shi, Wen Cai Wang","doi":"10.2478/acph-2025-0009","DOIUrl":"https://doi.org/10.2478/acph-2025-0009","url":null,"abstract":"This study aims to investigate the regulatory mechanisms of METTL3, YTHDF1, and the long non-coding RNA FOXD2-AS1 in the proliferation and apoptosis of esophageal cancer, with the goal of providing a basis for molecular diagnosis and targeted therapies. Gene expression was evaluated using qRT-PCR (METTL3/14) and Western blot analysis. The Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and Transwell assay were employed to assess cell proliferation and apoptosis. The EpiQuik m6A RNA Methylation Quantification Kit was utilized to quantify total m6A levels. The interaction between YTHDF1, FOXD2-AS1, and METTL3 was confirmed using RNA Binding Protein Immunoprecipitation (RIP), Co-Immunoprecipitation (CO-IP), and RNA pull-down assays. Methylated RNA Immuno preci pitation (MeRIP) was employed to assess the m6A modification levels of FOXD2-AS1. Tissue samples from animal models were analyzed via Hematoxylin-eosin staining (HE) staining and immunohisto-chemistry to assess METTL3 expression. The expression of METTL3 was up-regulated in esophageal cancer tissues and cells. Flow cytometry and CCK-8 detection showed that silencing METTL3 could inhibit the proliferation of esophageal cancer cells but accelerate their apoptosis. MeRIP-qPCR and Prediction of m6A-modified sites indicated that METTL3 regulated the m6A modification of FOXD2-AS1. In vitro and in vivo experiments showed that YTHDF1 binds to METTL3 and regulates the m6A modification of FOXD2-AS1 to affect esophageal cancer. Our results indicate that METTL3 regulates FOXD2-AS1 in an m6A-dependent manner through its interaction with YTHDF1, thereby influencing EC proliferation and apoptosis. This suggests a potential therapeutic target for the treatment of esophageal cancer.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"75 1","pages":"69-86"},"PeriodicalIF":2.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957214","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}

引用次数: 0

The impact of blood lipids and statins on renal function and mortality in patients with diabetic nephropathy: A meta-analysis. 血脂和他汀类药物对糖尿病肾病患者肾功能和死亡率的影响：荟萃分析。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-04-10 Print Date: 2025-03-01 DOI: 10.2478/acph-2025-0002

Dongqin Tian, Qian Chen, Lingli Zeng, Yan Hao

{"title":"The impact of blood lipids and statins on renal function and mortality in patients with diabetic nephropathy: A meta-analysis.","authors":"Dongqin Tian, Qian Chen, Lingli Zeng, Yan Hao","doi":"10.2478/acph-2025-0002","DOIUrl":"10.2478/acph-2025-0002","url":null,"abstract":"The aim of this study is to explore the impact of blood lipids and statins on renal function and all-cause mortality in patients with diabetic nephropathy (DN). PubMed, Embase, Web of Science, and Cochrane Library were systematically searched until April 9, 2024, for relevant studies of blood lipids and statins on renal function and all-cause mortality in patients with DN. After the selection, total cholesterol levels (TC), total triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate (eGFR), urinary albumin excretion (UAE), serum creati-nine (SCR), end-stage renal disease (ESRD), and all-cause mortality indexes were extracted for finally meta-analysis. In total, 25 papers containing 21,411 patients with DN were finally included in this study. Levels of TC and LDL-C, which are continuous variables, were higher in DN patients who developed ESRD [TC/weighted mean difference (WMD) = 0.517, 95 % confidence interval (CI): (0.223, 0.812), p = 0.001; LDL-C/WMD = 0.449, 95%CI: (0.200, 0.698), p < 0.001]. In addition, this study also observed that statins may reduce UAE levels [WMD = -46.814, 95% CI: (-71.767, -21.861), p < 0.001]. Finally, the survey indicated that statins may be associated with an ESRD reduction [HR = 0.884, 95% CI: (0.784, 0.998), p = 0.045]. Blood lipids, particularly TC and LDL-C, may slow the progression of DN to ESRD. Besides, statins may protect the kidneys by lowering the excretion of UAE levels and reducing the risk of ESRD. Based on the above outcomes, the findings of this study provided robust evidence-based medical support for the future prevention, surveillance, and management of DN.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":"1-22"},"PeriodicalIF":2.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833403","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}

引用次数: 0

Cloning, expression, and purification of recombinant AKR1D1 for therapeutic applications. 用于治疗的重组AKR1D1的克隆、表达和纯化。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-04-10 Print Date: 2025-03-01 DOI: 10.2478/acph-2025-0003

Kristina Shutevska, Aleksandra Kapedanovska Nestorovska

{"title":"Cloning, expression, and purification of recombinant AKR1D1 for therapeutic applications.","authors":"Kristina Shutevska, Aleksandra Kapedanovska Nestorovska","doi":"10.2478/acph-2025-0003","DOIUrl":"10.2478/acph-2025-0003","url":null,"abstract":"AKR1D1, a key enzyme in the aldo-keto reductase superfamily, plays a dual role in both steroid metabolism and bile acid synthesis by catalyzing the NADPH-dependent reduction of carbon-carbon double bonds, specifically converting 3-ketosteroid hormones into 5β-steroids. Positioned at the critical intersection of steroid hormone and bile acid metabolism, AKR1D1 has the potential to profoundly influence metabolic homeostasis and drug metabolism. Despite its importance, the enzyme's therapeutic implications and role in drug metabolism remain underexplored. This study presents an optimized methodology for the cloning, expression, and purification of AKR1D1 using an Escherichia coli expression system. We identified optimal conditions for ligation and precise DNA sequencing, emphasizing the need for lower DNA concentrations and higher purity. Protein expression was evaluated in E. coli strains BL21 and Rosetta, with the highest yields achieved under extended incubation at 25 °C with controlled IPTG concentrations. Using freshly transformed cells was essential for maintaining consistent protein expression. The enzyme's activity was confirmed using a spectrofluorometric assay, demonstrating efficient reduction of testosterone to 5β-DHT. This optimized methodology facilitates the production of AKR1D1 with high specific activity, establishing a valuable platform for future research. It enables a deeper investigation into AKR1D1's contributions to drug metabolism and its therapeutic potential.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":"147-157"},"PeriodicalIF":2.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833396","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}

引用次数: 0

Comparative efficacy and safety of vedolizumab and antitumor necrosis factor alfa in patients with inflammatory bowel diseases: A meta‑analysis. vedolizumab和抗肿瘤坏死因子在炎症性肠病患者中的比较疗效和安全性：一项荟萃分析

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-04-10 Print Date: 2025-03-01 DOI: 10.2478/acph-2025-0004

Yafang Li, Jin Ding, Chong Lu, Yiping Hong, Qunying Wang

{"title":"Comparative efficacy and safety of vedolizumab and antitumor necrosis factor alfa in patients with inflammatory bowel diseases: A meta‑analysis.","authors":"Yafang Li, Jin Ding, Chong Lu, Yiping Hong, Qunying Wang","doi":"10.2478/acph-2025-0004","DOIUrl":"10.2478/acph-2025-0004","url":null,"abstract":"This meta-analysis directly compares the efficacy and safety of vedolizumab and tumor necrosis factor-α (TNF-α) inhibitors for patients with inflammatory bowel disease (IBD), contrary to the previous one which provided an indirect comparison. In this meta-analysis, only the studies that directly compared two treatments (vedolizumab and TNF-α inhibitors) to each other (head-to-head approach) were considered. A comprehensive literature search was conducted using the following databases: PubMed, Embase, the Cochrane Library, and Web of Science. The pooled estimates of efficacies and safety were calculated as relative risk (RR) and 95 % confidence interval (CI). The presence of bias in the published material was evaluated using Begg's test. Sensitivity analysis was used to evaluate the pooled results' robustness. In total, 32 eligible studies were finally included. Results showed that the efficacy of vedolizumab was superior to TNF-α inhibitors in clinical remission [1.26, 95 % CI: 1.15-1.39]. Moreover, the vedolizumab group showed a reduced incidence of severe adverse events (RR = 0.63, 95 % CI: 0.42-0.94) compared to TNF-α inhibitors. Our results revealed superior efficacy and safety of vedolizumab compared to TNF-α inhibitors, which provided direct evidence for the use of vedolizumab in IBD treatment. Future studies are needed to confirm our findings.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":"23-40"},"PeriodicalIF":2.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603302","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}

引用次数: 0

Application of network pharmacology, bioinformatics, computational molecular docking, and experimental validation to study the anticancer effects of oleanolic acid in oral squamous carcinoma cells. 应用网络药理学、生物信息学、计算分子对接、实验验证等方法研究齐墩果酸对口腔鳞癌细胞的抗癌作用。

IF 2.1 4区医学

Acta Pharmaceutica Pub Date : 2025-04-10 Print Date: 2025-03-01 DOI: 10.2478/acph-2025-0005

Ting Yin, Hao Wang, Yaqin Zou

{"title":"Application of network pharmacology, bioinformatics, computational molecular docking, and experimental validation to study the anticancer effects of oleanolic acid in oral squamous carcinoma cells.","authors":"Ting Yin, Hao Wang, Yaqin Zou","doi":"10.2478/acph-2025-0005","DOIUrl":"https://doi.org/10.2478/acph-2025-0005","url":null,"abstract":"Oleanolic acid (OA) has demonstrated anticancer effects across various cancers, with some derivatives advancing to clinical trials. Howe ver, its precise mechanisms of action remain unclear, especially in oral squamous cell carcinoma (OSCC). This study employed network pharmacology, bioinformatics, molecular docking, dynamics simulations, and experimental validation to explore OA's anticancer effects in OSCC and elucidate its mechanism of action. OA's pharmacokinetic and physicochemical properties were assessed using SwissADME and Molsoft, revealing high oral bioavailability and GI absorption. SwissTargetPrediction and SuperPred identified protein targets, whereas GeneCards provided OSCC-related targets. A Venn diagram showed 34 overlapping targets between OA and OSCC. STRING and Cytoscape were used to construct a protein-protein interaction (PPI) network with 32 nodes and 164 edges, identifying HSP90AA1, STAT3, HSP90AB1, PI3KR1, and NFKB1 as key hub genes. Gene ontology and KEGG enrichment analyses highlighted relevant biological processes, molecular functions, and pathways. Molecular docking and dynamics simulations confirmed the strong binding of OA to hub targets. Experimental validation showed that OA inhibited cell viability and colony formation in a dose-dependent manner, induced apoptosis, and downregulated HSP90AA1, STAT3, and PI3KR1 proteins. In conclusion, this comprehensive study combining network pharmacology, bioinformatics, molecular simulations, and experimental assays provides valuable insights into OA's anticancer potential and detailed mechanism of action in OSCC.","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"75 1","pages":"41-68"},"PeriodicalIF":2.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952184","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}

引用次数: 0