ADMET and DMPK最新文献

{"title":"Nano-biomaterials in cancer therapy: Advances in targeting and overcoming cancer stem cell resistance.","authors":"Marzieh Dehghani, Behnam Hajipour-Verdom, Fatemeh Rahimzadeh, Parviz Abdolmaleki","doi":"10.5599/admet.3007","DOIUrl":"10.5599/admet.3007","url":null,"abstract":"<p><strong>Background and purpose: </strong>Cancer remains a leading cause of death globally, with long-term treatment success hindered by metastasis, recurrence, and therapy resistance. A central driver of these limitations is cancer stem cells (CSCs) - a rare subpopulation of tumour cells endowed with self-renewal and differentiation potential. CSCs contribute critically to tumour progression, metastatic spread, and resistance to conventional therapies, yet no clinically validated strategies currently exist to accurately detect or selectively eliminate them.</p><p><strong>Review approach: </strong>The paper systematically examined the literature on CSC origin, phenotypic characterization, isolation techniques, and mechanisms underlying resistance, including dormancy, enhanced DNA repair, apoptosis evasion, and microenvironmental protection. Particular attention was given to recent advances in nanomaterial-based strategies - metallic, carbon, and organic nanocarriers, designed to improve CSC-specific drug delivery, reactive oxygen species generation, pathway inhibition, and modulation of the CSC niche.</p><p><strong>Key results: </strong>Current CSC markers and in vivo models remain ambiguous and poorly standardized, limiting translational progress. Nanotechnology provides promising solutions by enabling targeted delivery and multi-functional therapy integration, yet most systems are still at the preclinical stage, constrained by issues of biocompatibility, targeting precision, and manufacturing scalability.</p><p><strong>Conclusion: </strong>Multifunctional nanoplatforms hold substantial potential to overcome CSC-driven resistance, improve therapeutic selectivity, and reduce recurrence. However, rigorous optimization and clinical validation are essential before these technologies can be integrated into routine oncology. This review advances understanding by outlining the intersection of CSC biology and nanomedicine, emphasizing translational pathways for CSC-targeted cancer therapy.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 5","pages":"3007"},"PeriodicalIF":4.3,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12662239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZnO-modified carbon paste electrode for electrochemical sensing of dopamine in the presence of tyrosine.","authors":"Ali Obaid Imarah, Nada Hasan, Mustafa G Alabbasi","doi":"10.5599/admet.3010","DOIUrl":"10.5599/admet.3010","url":null,"abstract":"<p><strong>Background and purpose: </strong>Dopamine, 3,4-dihydroxyphenylalanine, functions as a catecholamine neurotransmitter in the brain, sending messages to other neurons to regulate information transmission to other areas of the brain, govern movement, and alter brain activity. Tyrosine undergoes an enzymatic process in the pharmaceutical industry to produce dopamine. Thus, it is crucial to measure both tyrosine and dopamine in bodily fluids simultaneously.</p><p><strong>Experimental approach: </strong>In this work, we demonstrate the production of ZnO nanoparticles using a straightforward solvothermal technique. A straightforward, quick, and sensitive electrochemical sensing platform for dopamine detection was then created using the produced ZnO nanoparticles.</p><p><strong>Key results: </strong>Cyclic voltammetry comparison revealed that the ZnO/carbon paste electrode considerably enhanced the dopamine oxidation process compared to the unmodified carbon paste electrode (CPE). With a low detection limit of 0.003 μM, the ZnO/CPE sensor's linear response for voltammetric dopamine determination was found to be between 0.01 and 480.0 μM.</p><p><strong>Conclusion: </strong>The modified CPE effectively demonstrates its great accuracy in tyrosine-induced dopamine detection.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 6","pages":"3010"},"PeriodicalIF":4.3,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12755311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing through the blood-brain barrier: mechanisms, challenges and drug delivery strategies.","authors":"Ronny Vargas, Noelia Martinez-Martinez, Catalina Lizano-Barrantes, Jorge Andrés Pacheco-Molina, Encarna García-Montoya, Pilar Pérez-Lozano, Josep Mª Suñé-Negre, Carlos Suñé, Marc Suñé-Pou","doi":"10.5599/admet.2988","DOIUrl":"10.5599/admet.2988","url":null,"abstract":"<p><strong>Background and purpose: </strong>The delivery of therapeutics to the central nervous system (CNS) remains a major challenge due to the restrictive nature of the blood-brain barrier (BBB), a key evolutionary feature that preserves brain homeostasis. This review seeks to synthesize current knowledge on BBB composition, physiology, and transport mechanisms, and critically analyses drug delivery strategies aimed at overcoming this barrier and enabling effective CNS therapies.</p><p><strong>Approach: </strong>We conducted a comprehensive narrative review integrating evidence on BBB anatomy, transport and permeability mechanisms, drug delivery optimization strategies, with a particular focus on nanotechnology-based systems, and preclinical evaluation models.</p><p><strong>Key results: </strong>We highlight how a deeper understanding of BBB architecture and dynamic regulation can inform rational design of targeted strategies. Drug delivery approaches are summarized and compared, with emphasis on the potential of nanotechnology-based platforms to enhance CNS drug delivery. Translational considerations, including scalability, reproducibility, and regulatory requirements, are critically addressed. Major challenges identified include receptor saturation, competition with endogenous ligands, disease-specific variability in BBB permeability, and the limited predictive value of current preclinical models. Emerging tools, such as organ-on-chip (for evaluation) and microfluidic mixing (for manufacturing nanomaterials), offer promising means to improve physiological relevance and accelerate translation.</p><p><strong>Conclusion: </strong>Progress in BBB research has laid the groundwork for innovative therapies, but significant hurdles remain. Advancing CNS drug delivery will require collaborative work refining transport-targeting mechanisms, developing standardized preclinical models, and integrating fundamental research, applied nanomedicine, and regulatory science to open new opportunities for treating neurological and psychiatric disorders and brain tumours.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 5","pages":"2988"},"PeriodicalIF":4.3,"publicationDate":"2025-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12662247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pembrolizumab in PD-L1-positive advanced non-small cell lung carcinoma: A meta-analysis of survival benefits and immune-related toxicity events patterns.","authors":"Alendra Chakramurty, Adetya Rahma Dinni, Ihda Silvia, Aprilyan Laras Cantika, Citrawati Dyah Kencono Wungu","doi":"10.5599/admet.2956","DOIUrl":"10.5599/admet.2956","url":null,"abstract":"<p><strong>Background and objective: </strong>Pembrolizumab has shown significant therapeutic benefit in advanced non-small cell lung cancer (NSCLC), but it remains uncertain which patients will benefit the most, and recent data suggest that programmed death-ligand 1 (PD-L1) expression as a single predictive biomarker is insufficient. This systematic review and meta-analysis looked at the safety and efficacy of pembrolizumab in PD-L1-positive advanced NSCLC patients, with a particular focus on disparities in treatment response to PD-L1 level of expression and demographic characteristics.</p><p><strong>Method: </strong>According to the PRISMA 2020 guidelines, six large databases were searched up to March 2025 for randomized controlled trials comparing pembrolizumab with chemotherapy in patients with such conditions. Overall survival (OS) and progression-free survival (PFS) were chosen as primary outcomes, and overall response rate (ORR) and safety profiles as secondary endpoints. A meta-analysis was conducted using a random-effects model, and the Cochrane risk of bias (ROB2) tool was employed to evaluate study quality. Seven randomized controlled trials involving 4,900 patients were included in the analysis.</p><p><strong>Key results: </strong>Pembrolizumab had a substantially better performance compared to chemotherapy for all the measures of efficacy: OS (hazard ratio (HR) 0.65, 95 % confidence interval (CI): 0.57 to 0.73, <i>P</i> < 0.00001), PFS (HR 0.55, 95 % CI: 0.42 to 0.72, <i>P</i> < 0.0001) and ORR (relative risk 2.10, 95 % CI: 1.51 to 2.93, <i>P</i> < 0.0001). Subgroup analysis showed greater survival benefit in patients younger than 65 years (OS HR 0.55) compared to patients aged 65 and older (OS HR 0.72), and in females (OS HR 0.44) compared to males (OS HR 0.67). Of most significant importance, those with PD-L1 expression <1 % also saw considerable benefit in survival (OS HR 0.60), casting doubts over the existing biomarker-based selection criteria.</p><p><strong>Conclusion: </strong>In conclusion, pembrolizumab achieves clinically meaningful survival benefits and an acceptable toxicity in PD-L1-positive advanced NSCLC. The high efficacy observed even in low PD-L1 expressers, and demographic differences in drug response, suggest that existing patient selection criteria could potentially be extended. These findings justify the application of a more advanced approach involving multiple biomarkers for more precise treatment allocation.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 5","pages":"2956"},"PeriodicalIF":4.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12662249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficient electrochemical determination of dopamine in the presence of uric acid in real samples using tungsten disulfide nanostructure modified electrode.","authors":"Ibrahim Ayad Jihad, Thekrayat Joodi Jassim, Zainab Naeif Mageed","doi":"10.5599/admet.2968","DOIUrl":"10.5599/admet.2968","url":null,"abstract":"<p><strong>Background and purpose: </strong>Research on the detection of uric acid (URA) and dopamine (DPA) is ongoing because of the difficulties posed by their closely overlapping oxidation potentials. Tungsten disulfide nanostructures have become attractive electrode materials to address this problem due to their low toxicity, low cost, easy production, and strong catalytic activity.</p><p><strong>Experimental approach: </strong>For voltammetric detection of compounds, we present the creation of an electrochemical sensor based on a glassy carbon electrode modified with tungsten disulfide nanostructures.</p><p><strong>Key results: </strong>According to electrochemical analyses, the manufactured sensor performed exceptionally well, having a broad LDR of 0.03 to 600.0 μM and a low LOD of 10 nM for DPA.</p><p><strong>Conclusion: </strong>The effective detection of compounds in real samples, such as injections and urine, with acceptable recovery rates further confirmed the suggested sensor's practical usefulness. In addition to offering a viable method for creating tungsten disulfide-based modified electrodes, this study holds promise for future applications in bioanalytical sensing and clinical diagnostics.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 6","pages":"2968"},"PeriodicalIF":4.3,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12755309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a carbon paper-based electrochemical immunosensor for trimethoprim detection in fishery species: monitoring antibiotic contaminants.","authors":"Maria Freitas, Vitória Dibo, Rita Ribeiro, Cristina Delerue-Matos, Simone Morais, Álvaro Torrinha","doi":"10.5599/admet.2962","DOIUrl":"10.5599/admet.2962","url":null,"abstract":"<p><strong>Background and purpose: </strong>Monitoring antibiotic drugs in the environment is particularly relevant given their role in fostering microbial resistance, impacting aquatic species and human health. Therefore, this work addresses the lack of a sustainable and cost-effective analytical approach and reports the development of a competitive electrochemical immunosensor for the rapid analysis of trimethoprim (TMP), an aquatic contaminant of emerging concern, overcoming the limitations of conventional methods that are often costly and time-consuming.</p><p><strong>Experimental approach: </strong>A miniaturized 3-electrode system was developed to support the analyses of a low-volume sample (200 μL), using a low-cost carbon-paper working electrode, pencil graphite lead auxiliary electrode and a stainless-steel needle reference electrode. Scanning electron microscopy was used to characterize the transducer, revealing a network of randomly arranged carbon fibres, significant for efficient antibody immobilization. For the immunoassay construction, an anti-TMP antibody was physically adsorbed to a small-sized transducer (<i>d</i> = 4 mm) for the specific recognition of TMP, followed by incubation with the enzyme-conjugate (horseradish peroxidase) and the enzyme-substrate (tetramethylbenzidine).</p><p><strong>Key results: </strong>The analytical signal was recorded by chronoamperometry (1-minute reaction) and yielded a limit of detection of 34 ng L^-1. The 45-minute assay demonstrates accuracy (92.0 to 103.2 % in fishery species including codfish, mackerel, crab, and hake), reproducibility (6.1 and 9.3 % for repeatability and inter-day variation coefficient) and high selectivity (bias less than 5 %) analysis. The sensor's performance was validated against a conventional Enzyme-Linked Immunosorbent Assay.</p><p><strong>Conclusion: </strong>This study introduces a sustainable electrochemical immunosensor, offering a portable and eco-friendly alternative for the rapid detection of TMP in fishery species, addressing the limitations of traditional methods.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 6","pages":"2962"},"PeriodicalIF":4.3,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12755313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A simple UiO-66-NH₂@MWCNTs based electrochemical sensor for the sensitive detection of metronidazole.","authors":"Noor Abd Alkhudhur Salman, Israa A Jassem, Isam Nghaimesh Taeb","doi":"10.5599/admet.2940","DOIUrl":"10.5599/admet.2940","url":null,"abstract":"<p><strong>Background and purpose: </strong>Metronidazole (MRNZ) is a highly efficacious pharmacological agent for treating protozoal infections, including trichomoniasis, giardiasis, and disorders caused by anaerobic bacteria.</p><p><strong>Experimental approach: </strong>In the present investigation, a solvothermal approach is employed to synthesize a composite of multiwalled carbon nanotubes (MWCNTs-COOH) with UiO-66-NH₂, resulting in the formation of UiO-66-NH₂@MWCNTs. Given the exceptional electrocatalytic characteristics of the UiO-66-NH₂@MWCNTs nanocomposite, it was selected as the sensing material and subsequently integrated onto the surface of a bare screen-printed carbon electrode.</p><p><strong>Key results: </strong>Under optimal experimental conditions, the developed electrochemical sensor exhibited outstanding metrics of repeatability, stability, selectivity, and reproducibility for detection across an extensive concentration range, specifically from 0.5 to 350.0 μM, while achieving a limit of detection of 0.1 μM. Furthermore, the practical application of the sensor was rigorously assessed using MRNZ tablet samples and urine specimens, resulting in a commendable recovery rate of MRNZ, ranging from 97.3 to 104.0 %.</p><p><strong>Conclusion: </strong>This research elucidates a straightforward, expedited, and significant methodology for the application of UiO-66-NH₂@MWCNTs within the domain of electrochemical sensing.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 6","pages":"2940"},"PeriodicalIF":4.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12755316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction between albumin originating from persons with uncontrolled diabetes mellitus type 2 and food antioxidants.","authors":"Miloš Šunderić, Dragana Dekanski, Olgica Nedić","doi":"10.5599/admet.2892","DOIUrl":"10.5599/admet.2892","url":null,"abstract":"<p><strong>Background and purpose: </strong>Dietary interventions are a cornerstone in the management of type 2 diabetes mellitus. The efficiency, however, depends on pharmacokinetic factors, including the interaction of food ingredients with plasma proteins. The concept of this study was to investigate the binding effects of three pronounced antioxidants present in the Mediterranean diet: resveratrol, (dihydro)lipoic acid and oleuropein, with albumin isolated from persons with diabetes (HbA1c 63±7 mmol/mol, or 7.9±0.6%) and healthy persons, carrying its intrinsic ligands.</p><p><strong>Experimental approach: </strong>Spectrofluorometric analysis, native electrophoresis and immunoblotting were performed with albumin before and after the interaction with antioxidants.</p><p><strong>Key results: </strong>Fluorescence spectra of the protein from two study groups were similar, whereas a spectrum of methylglyoxal-modified albumin (<i>in vitro</i> oxidised) was different. Calculated binding constants were also similar for the two study groups for all three ligands. Kinetic fluorescence measurements revealed significantly altered activity of albumin-bound (dihydro)lipoic acid in persons with diabetes compared to healthy individuals, and no significant difference in the activity of resveratrol in expressing antioxidant protection of albumin upon its exposure to oxidative stress.</p><p><strong>Conclusions: </strong>Although the findings should be further validated using other antioxidants and glycated albumin derived from persons stratified according to the severity of a disease, the results have documented that <i>in vitro</i> methylglyoxal-oxidised albumin, routinely employed for diabetes-simulated investigations, was shown not to reflect this pathophysiological condition properly and not to be adequate for the assessment of relevant nutritional/biochemical potential of food antioxidants.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 5","pages":"2892"},"PeriodicalIF":4.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12662243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrochemical sensing and quantification of theobromine in cocoa products at polyvaline functionalized graphite paste sensor electrode.","authors":"Battira Madappa Sharmila, Jamballi G Manjunatha","doi":"10.5599/admet.2928","DOIUrl":"10.5599/admet.2928","url":null,"abstract":"<p><strong>Background and purpose: </strong>Theobromine (THB), an alkaloid present in various plants, is widely used in pharmaceutical formulations and food products. Increased consumption leads to health risks in both humans and animals.</p><p><strong>Experimental approach: </strong>An electrochemically polymerized polyvaline-modified graphite paste sensor (PVMGPS) was developed in this work to investigate the mechanistic and kinetic pathways of the electrooxidation of THB. Electrochemical impedance spectroscopy and scanning electron microscopy were used for characterizing the designed sensors. The fabricated PVMGPS under optimal conditions produced enhanced current responses compared to the bare graphite paste sensor (BGPS). Multiple parameters were investigated using cyclic voltammetry and differential pulse voltammetry.</p><p><strong>Key results: </strong>The electroactive surface areas of the BGPS and PVMGPS were evaluated as 0.025 and 0.252 cm², respectively. The study of the effect of pH of phosphate buffer solution (PBS) and further analysis revealed that the electro-oxidation involves equivalent numbers of electrons and protons. Scan rate dependence revealed that the oxidation of THB proceeds through diffusion-controlled kinetics. The limit of detection and limit of quantification were evaluated to be 1.22 and 4.08 μM, respectively. Moreover, the voltammetric assay demonstrated a good recovery rate, proving the efficacy of the proposed sensor in detecting THB-containing food samples.</p><p><strong>Conclusions: </strong>The outcome of the analysis substantiated the efficacy, selectivity and sensitivity of the developed novel sensor for THB detection.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 6","pages":"2928"},"PeriodicalIF":4.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12755312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New xanthone and chemical constituents from the aerial parts of <i>Mallotus glomerulatus</i> and their cytotoxicity in MCF-7 and MDA-MB-231 breast cancer cells.","authors":"Napason Chabang, Chanikarn Wongwitayasombat, Patoomratana Tuchinda, Bamroong Munyoo, Niwat Kangwanrangsan, Suradej Hongeng, Bodee Nutho, Sitthivut Charoensutthivarakul, Phongthon Kanjanasirirat","doi":"10.5599/admet.2901","DOIUrl":"10.5599/admet.2901","url":null,"abstract":"<p><strong>Background and purpose: </strong>Breast cancer remains a significant global health burden, especially in low-resource settings where standard therapies are limited. This study aimed to explore <i>Mallotus glomerulatus</i>, a lesser-known Thai medicinal plant, as a potential source of novel anti-breast cancer agents.</p><p><strong>Experimental approach: </strong>A phytochemical investigation of <i>M. glomerulatus</i> resulted in the isolation and structural characterization of a novel xanthone (Compound <b>1</b>) and cleistanthin A (Compound <b>10</b>) using UV, IR, NMR, and HRMS techniques. Cytotoxicity of the compounds was evaluated in vitro against MCF-7 (ER-positive) and MDA-MB-231 (triple-negative) breast cancer cell lines, along with HepG2 liver cells. Molecular docking studies were conducted to assess their interaction with vacuolar H⁺-ATPase (V-ATPase).</p><p><strong>Key results: </strong>Compound <b>1</b> demonstrated selective cytotoxicity toward MCF-7 cells, whereas cleistanthin A exhibited potent cytotoxicity against both breast cancer lines, with nanomolar IC₅₀ values and a high selectivity index (>100) for MDA-MB-231 compared to HepG2 cells. Docking analysis revealed favourable binding of both compounds at the a-c subunit interface of V-ATPase, suggesting a mechanism involving proton pump inhibition and lysosomal dysfunction.</p><p><strong>Conclusion: </strong>The findings highlight <i>M. glomerulatus</i>, particularly cleistanthin A, as a promising source of safe and affordable anti-breast cancer compounds with potential therapeutic value. Further studies on the mechanism and <i>in vivo</i> efficacy are warranted.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 5","pages":"2901"},"PeriodicalIF":4.3,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12662241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}