ADMET and DMPK最新文献

{"title":"Titanium dioxide nanoparticle-modified screen-printed electrode for erlotinib determination.","authors":"Pooja Das Manjulabhai, Sruthi Mundangadan, Maria Paul, Srinivedha Lal, Namitha Ramalal, Mariya Anto, Dhanya Gangadharan","doi":"10.5599/admet.3437","DOIUrl":"10.5599/admet.3437","url":null,"abstract":"<p><strong>Background and purpose: </strong>Erlotinib (ERL), a first-generation epidermal growth factor receptor tyrosine kinase inhibitor drug that is used in non-small cell lung cancer treatment, requires precise therapeutic drug monitoring owing to its narrow therapeutic window and significant inter-patient pharmacokinetic variability; existing chromatographic methods, while robust, are resource-intensive and incompatible with point-of-care settings, necessitating the development of simpler, cost-effective electroanalytical alternatives.</p><p><strong>Experimental approach: </strong>A titanium dioxide nanoparticle-modified screen-printed electrode (TiO₂NP@SPE) was fabricated via a facile single-step modification and comprehensively characterized by scanning electron microscopy - energy dispersive X-ray Analysis, Fourier transform infrared spectroscopy, X-ray diffraction and electrochemical impedance spectroscopy; electrochemical performance was evaluated by cyclic voltammetry and differential pulse voltammetry, and analytical validation was performed in human serum using the standard addition method.</p><p><strong>Key results: </strong>The TiO₂NP@SPE demonstrated markedly enhanced electron transfer kinetics over the bare SPE, yielding a well-defined linear response with a competitive limit of detection, high sensitivity, and intra- and inter-day serum recoveries within acceptable precision limits, alongside excellent selectivity against physiologically relevant interferents and structurally related anticancer agents.</p><p><strong>Conclusion: </strong>This work developed a disposable screen-printed electrode sufficient to achieve sensitive, selective, and accurate quantification of ERL in human serum using TiO₂NP@SPE as a promising, clinically translatable platform for point-of-care therapeutic drug monitoring in oncology; future efforts should address the elevated detection limit relative to the bare electrode and extend validation to real patient plasma samples to fully confirm clinical applicability.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"14 ","pages":"3437"},"PeriodicalIF":5.1,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786998","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":"Bimetallic metal organic framework modified screen printed electrode for simultaneous voltammetric determination of calcium folinate and methotrexate.","authors":"Ameer Mahmood Shaker, Batool Nassir Hamran, Ala'a R Shaker, Hussein Ali Al-Bahrani","doi":"10.5599/admet.3487","DOIUrl":"10.5599/admet.3487","url":null,"abstract":"<p><strong>Background and purpose: </strong>Calcium folinate (CFT) is a medication used as an antidote to methotrexate (MTT) and as a vitamin against anaemia. MTT is used to treat a variety of carcinomas, including acute lymphoblastic leukaemia, head and neck cancer, gastric cancer, breast cancer and choriocarcinoma.</p><p><strong>Experimental approach: </strong>A nanocomposite made of Fe and Mg linked to a 1,4-benzene dicarboxylate ligand metal organic framework (FeMg-BDC MOF) was created for this investigation. Using field emission scanning electron microscopy, the morphology and structure of the Mg-BDC MOF were examined. Next, a screen-printed electrode modified with a synthetic nanocomposite (FeMg-BDC MOF/SPE) was used as the working electrode for voltammetric detection of CFT.</p><p><strong>Key results: </strong>The FeMg-BDC MOF/SPE demonstrated high electrocatalytic activity for CFT oxidation as compared to unmodified SPE. The limit of detection is 0.04 μM, and under ideal conditions, the oxidation peak currents of CFT show a linear relationship with its concentration in the range of 0.1 to 390.0 μM. Additionally, when MTT was present, the FeMg-BDC MOF/SPE demonstrated good activity toward CFT determination. The separation of the oxidation peak potentials (255 mV) indicates that differential pulse voltammetry can be used to detect these two medications simultaneously.</p><p><strong>Conclusion: </strong>The devised sensor's applicability was confirmed with outstanding results using CFT and MTT assays in pharmaceutical specimens and urine samples.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"14 ","pages":"3487"},"PeriodicalIF":5.1,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786874","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":"From nanoscale to clinic: The growing impact of nanotechnology in translational drug delivery.","authors":"Ronny Vargas, Fabiola Martos-Kikut, Noelia Martinez-Martinez, Esteban Lara-Guerrero, Catalina Lizano-Barrantes, Jorge Andrés Pacheco-Molina, Miquel Romero-Obon, Khadija Rouaz-El-Hajoui, Encarna García-Montoya, Pilar Pérez-Lozano, Carlos Suñé, Marc Suñé-Pou","doi":"10.5599/admet.3495","DOIUrl":"10.5599/admet.3495","url":null,"abstract":"<p><strong>Background and purpose: </strong>From the early use of liposomes in the 1960s to modern nucleic acid delivery platforms, nanotechnology has shown its value in drug delivery and diagnostic applications. A wide range of nanostructures has been investigated for drug delivery, including inorganic, polymeric and lipid-based nanomaterials. While some of these nanomaterials have reached more advanced stages of clinical development, some even reaching commercialization, new alternatives are continuously being explored.</p><p><strong>Approach: </strong>This review describes the different categories of nanomaterials being used as nanocarriers and provides concrete representative examples of commercially approved products.</p><p><strong>Key results: </strong>Current trends of nanotechnology developments in the pharmaceutical market largely focus on the treatment of cancer, infectious diseases, central nervous system disorders and cardiovascular diseases. At the same time, lipid nanoparticle platforms are gaining relevance in current development pipelines. However, some of the main challenges limiting clinical translation include manufacturability, scale-up, long-term stability, regulatory uncertainty, intellectual property issues and the lack of representative preclinical study models.</p><p><strong>Conclusion: </strong>Nanotechnology has become a fundamental breakthrough in medicine, especially for advanced therapies such as gene silencing or gene editing alternatives. All things considered, no universal nanocarrier fits all biomedical applications; the evolution of the field depends on several platforms demonstrating their individual potential.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"14 ","pages":"3495"},"PeriodicalIF":5.1,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786912","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":"Extracellular vesicles and their translational therapeutic potential.","authors":"Riya Mukherjee, Ramendra Pati Pandey, Chung Ming Chang","doi":"10.5599/admet.3328","DOIUrl":"10.5599/admet.3328","url":null,"abstract":"<p><strong>Background and purpose: </strong>Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising cell-free therapy for osteoarthritis (OA). However, their transition into clinical therapeutics is constrained by unstandardized pharmacokinetics and heterogeneous preclinical reporting.</p><p><strong>Experimental approach: </strong>A meta-analysis of preclinical in vivo OA models evaluating MSC-EV therapy was conducted. Study quality was rigorously assessed using MISEV 2023 (Minimal Information for Studies of Extracellular Vesicles, 2023) criteria and the SYRCLE (Systematic Review Centre for Laboratory animal Experimentation) risk-of-bias tool. Quantitative synthesis was performed for the Osteoarthritis Research Society International (OARSI) histological score, reporting pooled mean differences (MDs) and 95 % confidence intervals (95% CIs), along with heterogeneity (<i>I</i> ² statistic) and microRNA (miRNA) cargo analysis.</p><p><strong>Key results: </strong>MSC-EV administration conferred robust structural protection against cartilage degradation. Quantitative synthesis of human-derived MSC-EVs (26 studies) significantly reduced OARSI scores (MD -3.27, 95% CI -4.66 to -1.88; <i>p</i> < 0.0001). Similarly, quantitative synthesis of animal-derived MSC-EVs (8 studies) demonstrated an even more profound effect (MD -5.58, 95% CI -7.13 to -4.03; <i>p</i> < 0.0001). Non-parametric Trim-and-Fill analysis estimated zero missing studies in both datasets, confirming that these effect sizes are highly robust to publication bias. Despite these robust efficacy signals, significant heterogeneity (<i>I</i> ² > 84 %) persisted. Meta-regression revealed that arbitrary dosage metrics, whether reported by particle count or protein concentration, failed to reliably predict treatment efficacy, highlighting severe gaps in dose-exposure standardization.</p><p><strong>Conclusion: </strong>MSC-EVs demonstrate highly potent, cross-species efficacy in attenuating OA progression. However, clinical translation is critically bottlenecked by a lack of ADMET (absorption, distribution, metabolism, excretion and toxicity) compliance. Future research must prioritize standardized particle-based dosing, in vivo pharmacokinetic tracking, and rigorous cargo-function validation to enable regulatory approval.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"14 ","pages":"3328"},"PeriodicalIF":5.1,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786922","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":"Experimentally derived biomimetic chromatographic descriptors for drug-induced phospholipidosis liability prediction.","authors":"Chrysanthos Stergiopoulos, Valko Klara","doi":"10.5599/admet.3460","DOIUrl":"10.5599/admet.3460","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and purpose: &lt;/strong&gt;Drug-induced phospholipidosis (PLD) is a complex intracellular liability commonly associated with the lysosomal accumulation of cationic amphiphilic drugs and remains an important concern in drug development because of its implications for safety, intracellular disposition, and compound prioritization. Although cationic amphiphilicity, membrane interactions, and lysosomal trapping are established features of PLD, experimentally accessible descriptors that capture PLD-relevant membrane affinity remain valuable for early-stage risk assessment. This study aimed to evaluate whether biomimetic chromatographic descriptors can improve the prediction and interpretation of PLD liability by providing experimentally derived information on membrane affinity and protein-binding-related distributional behavior.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Experimental approach: &lt;/strong&gt;A curated dataset of 65 compounds with experimentally reported PLD responses was analyzed using multiple linear regression and ordinal classification approaches. PLD potency was expressed as pEC₅₀, while ordinal models classified compounds into non-inducers, weak/moderate inducers, and strong inducers. Membrane affinity was quantified using immobilized artificial membrane chromatography, expressed as CHI IAM, while protein-related interactions were represented by human serum albumin affinity, log &lt;i&gt;k&lt;/i&gt; &lt;sub&gt;HSA&lt;/sub&gt;, and α&lt;sub&gt;1&lt;/sub&gt;-acid glycoprotein affinity, log k&lt;sub&gt;AGP&lt;/sub&gt;. Biomimetic chromatographic descriptors were compared with conventional physicochemical parameters, including log P and log D, to assess their relative predictive and mechanistic value.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Key results: &lt;/strong&gt;CHI IAM-containing models showed strong predictive performance for PLD potency, with external predictivity reaching Q&lt;sup&gt;2&lt;/sup&gt; &lt;sub&gt;ext&lt;/sub&gt; = 0.823. CHI IAM alone also performed strongly, achieving Q&lt;sup&gt;2&lt;/sup&gt; &lt;sub&gt;ext&lt;/sub&gt; = 0.821, indicating that membrane affinity captures a major component of PLD-relevant behavior. In ordinal classification models, CHI IAM alone provided robust discrimination of PLD severity, with a test accuracy of 0.769, macro F1 score of 0.778, and macro-AUC of 0.923. Protein-binding descriptors, particularly log k&lt;sub&gt;AGP&lt;/sub&gt;, showed moderate predictive value but offered limited, model-dependent improvement once membrane affinity was considered. Conventional lipophilicity descriptors did not outperform the biomimetic membrane-affinity descriptor.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Biomimetic chromatographic descriptors provide experimentally derived, mechanistically interpretable surrogates for assessing early-stage PLD liability. CHI IAM offers a practical approximation of membrane-affinity behavior relevant to lysosomal phospholipid accumulation and PLD risk. Protein-binding descriptors may provide complementary information related to distributional phenotypes, but their added value appears less consistent than that of membrane af","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"14 ","pages":"3460"},"PeriodicalIF":5.1,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786910","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":"Zn-Ni metal-organic framework nanosheets@graphene oxide nanocomposite: A promising voltammetric platform for sensitive determination of doxorubicin.","authors":"Tahereh Kondori, Niloufar Akbarzadeh-T, Somayeh Tajik, Hadi Beitollahi","doi":"10.5599/admet.3384","DOIUrl":"10.5599/admet.3384","url":null,"abstract":"<p><strong>Background and purpose: </strong>Doxorubicin (DOX) serves as an anthracycline-based chemotherapy drug to treat multiple types of cancers and sarcomas, which include lung, breast, bladder, leukaemia, liver, head and neck cancers.</p><p><strong>Experimental approach: </strong>The electroanalysis of the trace level of DOX in this study was conducted using a Zn-Ni metal-organic framework nanosheets@graphene oxide nanocomposite (Zn-Ni MOF NSs@GO) after the modification of a screen-printed carbon electrode (Zn-Ni MOF NSs@GO/SPCE). Using chronoamperometry, cyclic voltammetry and differential pulse voltammetry, the electrochemical characteristics of the sensor as constructed for DOX measurement were examined.</p><p><strong>Key results: </strong>Consequently, the composite sensor demonstrated exceptional electrocatalytic performance in oxidizing DOX within a concentration range of 0.004 to 190.0 μM, with a detection limit of 0.001 μM. It was found that the Zn-Ni MOF NSs@GO/SPCE was effective at determining DOX in real samples, with good recovery values in the 97.1 to 102.0 % range.</p><p><strong>Conclusion: </strong>The designed sensor with cost-effective and good performance could be valuable for therapeutic drug monitoring and clinical diagnostics.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"14 ","pages":"3384"},"PeriodicalIF":5.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787029","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":"Comprehensive review of biosynthesis, plant function, metabolism and new therapeutic bioactivities of flavonoids.","authors":"Iman Permana Maksum, Tati Herlina, Teruna J Siahaan, Yaya Rukayadi, Meiske Naomi Mamuaja","doi":"10.5599/admet.3404","DOIUrl":"10.5599/admet.3404","url":null,"abstract":"<p><strong>Background and purpose: </strong>Flavonoids are polyphenolic secondary metabolites synthesized via the phenylpropanoid pathway, serving as a vital biological \"immune system\" for plants by providing UV-B protection, antimicrobial defence, and pollinator attraction.</p><p><strong>Experimental approach: </strong>This review examines how these plant-based survival tools translate into potent therapeutic agents for human health through a literature review using Google Scholar, Scopus and ScienceDirect, with keywords alone or in combination with other terms.</p><p><strong>Key results: </strong>Current research demonstrates that flavonoids possess diverse bioactivities, including antioxidant, anti-inflammatory neuroprotective properties, with significant efficacy in mitigating cardiovascular disease, diabetes and cancer. Despite these benefits, the clinical application of flavonoids is currently hindered by limited bioavailability, which prevents consistent therapeutic concentrations in the human body, and a lack of standardized regulatory dosing.</p><p><strong>Conclusion: </strong>This paper identifies three critical pillars for future innovation in the development of structural analogs to (a) improve intestinal absorption, (b) explore drug synergy for enhancing conventional medical treatments and (c) evaluate the microbiome interactions to facilitate personalized nutrition. By integrating plant biochemistry with clinical pharmacology, flavonoids can be transitioned from general dietary components into precise, evidence-based therapies.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"14 ","pages":"3404"},"PeriodicalIF":5.1,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786902","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":"Mechanisms of action of the hexane extract of <i>Hypericum brasiliense</i> and its component uliginosin B against drug-resistant <i>Staphylococcus aureus</i>.","authors":"Julia Chaves Scaffo, Sofia Trindade Mussi da Silva, Vitor Won-Held Rabelo, Leandro Stefano Sangenito, Lucas da Silva Abreu, Thaís P Mello, Leandro Rocha, André Luis Souza Dos Santos","doi":"10.5599/admet.3333","DOIUrl":"10.5599/admet.3333","url":null,"abstract":"<p><strong>Background and purpose: </strong>Microbial resistance is a major global health concern. Methicillin-resistant Staphylococcus aureus is particularly relevant due to its clinical significance, virulence and adaptability. In the search for novel antimicrobial agents, natural products emerged as important sources of bioactive molecules. Previous studies have identified <i>Hypericum brasiliense</i> as a plant with promising antibacterial properties.</p><p><strong>Experimental approach: </strong>We evaluated the susceptibility, mechanisms of action and toxicity of <i>H. brasiliense</i> hexane extract (heHb) and the isolated compounds uliginosin B (uliB), isouliginosin B and japonicin A against reference and drug-resistant <i>S. aureus</i> isolates.</p><p><strong>Key results: </strong>The heHb and uliB demonstrated strong antibacterial activity, exhibiting MICs of 3.125 to 6.25 μg mL^-1 and MBCs of 6.25 to 12.5 μg mL^-1. Isouliginosin B displayed moderate activity (MIC = 12.5 μg mL^-1; MBC ≤50 μg mL^-1), whereas japonicin A was inactive. Transmission and scanning electron microscopy revealed pronounced ultrastructural alterations in bacterial cells following exposure to either heHb or uliB, and these exposures induced oxidative stress without compromising plasma membrane integrity. Conversely, the antioxidant N-acetylcysteine partially restored bacterial growth. Docking analysis suggested that uliB might act as a competitive substrate for the NADH-2 enzyme and cytochrome bd oxidase. Moreover, heHb and uliB inhibited biofilm formation and disrupted mature biofilms. Cytotoxicity assays (Vero and HaCaT lineages) showed CC₅₀ >90 μg mL^-1, and haemolysis occurred only at the highest concentrations. <i>In vivo</i> assessment using <i>Galleria mellonella</i> confirmed low toxicity. ADMET predictions indicated a favourable pharmacokinetic profile for uliB.</p><p><strong>Conclusion: </strong>UliB is likely a key bioactive compound of <i>H. brasiliense</i>, with promising therapeutic potential against S. aureus.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"14 ","pages":"3333"},"PeriodicalIF":5.1,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786843","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 detection of illicit sibutramine adulteration in herbal weight-loss products using an AgNPs-ErGO modified electrode.","authors":"Nguyen Dang Thuy Anh, Vo Thi Cam Le, Huynh Van Chung, Ngo Thi Thanh Xuan, Hoang Thi Minh Nguyet, Pham Thi Thanh Ha, Ha Thuy Trang, Le Hoang Hao, Dao Thi Cam Minh, Nguyen Hai Phong, Dinh Quang Khieu","doi":"10.5599/admet.3433","DOIUrl":"10.5599/admet.3433","url":null,"abstract":"<p><strong>Background and purpose: </strong>Sibutramine is a synthetic anti-obesity drug that has been banned or restricted in many countries due to serious cardiovascular risks. However, its illegal adulteration in herbal weight-loss products remains a public health concern. This study aimed to develop a simple, sensitive, and reliable electrochemical method for the determination of sibutramine in herbal weight-loss products using a silver-nanoparticle-electrochemically reduced graphene oxide modified glassy carbon electrode.</p><p><strong>Experimental approach: </strong>Graphene oxide, electrochemically reduced graphene oxide, silver nanoparticles and AgNPs-ErGO nanocomposite were synthesized and characterized using X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy combined with energy dispersive X-ray spectroscopy, Raman spectroscopy and high-resolution transmission electron microscopy. The AgNPs-ErGO-modified glassy carbon electrode was fabricated and used for sibutramine detection by linear sweep voltammetry. Experimental parameters affecting the analytical signal were optimized. The method was validated according to AOAC guidelines and compared with an HPLC-DAD reference method.</p><p><strong>Key results: </strong>The AgNPs-ErGO/GCE exhibited improved electrochemical response toward sibutramine compared with bare and other modified electrodes. The developed method showed good selectivity, linearity, precision, accuracy, and sensitivity for sibutramine determination. Application to commercial herbal weight-loss samples demonstrated the suitability of the proposed method for real sample analysis, with results comparable to those obtained by HPLC-DAD.</p><p><strong>Conclusion: </strong>The AgNPs-ErGO/ /GCE-based electrochemical method provides a rapid, cost-effective, and reliable approach for detecting sibutramine adulteration in herbal weight-loss products. This work contributes to the development of practical analytical tools for quality control and consumer safety monitoring.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"14 ","pages":"3433"},"PeriodicalIF":5.1,"publicationDate":"2026-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786853","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":"Cholinesterases inhibition profiles with Ugi-derived peptidemimetics: A combined experimental and computational study.","authors":"Alma Ramić, Toni Divjak, Lucija Hadrović, Matej Pavlinić, Ana Matošević, Anita Bosak, Jakov Borovec, Bruna Bakota, Tomica Hrenar, Ines Primožič","doi":"10.5599/admet.3292","DOIUrl":"10.5599/admet.3292","url":null,"abstract":"<p><strong>Background and purpose: </strong>Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are crucial enzymes implicated in various neurological disorders, including Alzheimer's disease. Developing selective inhibitors for either enzyme is one of the key therapeutic strategies. This study aimed to synthesize and evaluate a novel series of peptidomimetics for their ability to inhibit both human AChE and BChE, with a focus on identifying compounds exhibiting joint inhibitory activity or selectivity for BChE.</p><p><strong>Experimental approach: </strong>Eleven peptidomimetics were synthesized using the Ugi four-component reaction. <i>In vitro</i> enzyme inhibition assays were performed to determine the dissociation constants (<i>K</i> _i) for both human AChE (hAChE) and human BChE (hBChE). Principal component analysis was employed to analyse the inhibition data and map compound selectivity. To investigate the molecular interactions between the peptidomimetics and the BChE active site, quantum-chemical docking simulations were conducted.</p><p><strong>Key results: </strong>All synthesized compounds exhibited reversible, micromolar inhibition of both hAChE and hBChE. Two compounds demonstrated significant BChE selectivity, with 279- and 169-fold higher preference for BChE, respectively. Principal component analysis revealed distinct clusters correlating with preferential binding to either enzyme. Docking simulations supported these findings, highlighting key stabilizing interactions (primarily π-π stacking) between the peptidomimetics and BChE, explaining superior selective and joint inhibitory activity.</p><p><strong>Conclusion: </strong>This work demonstrates the successful synthesis and characterization of novel peptidomimetics with varying degrees of hAChE and hBChE inhibition, including compounds with notable BChE selectivity. The combination of experimental data and computational modelling provides valuable insights into the structural basis of enzyme inhibition and establishes a foundation for rational design of more potent and selective cholinesterase inhibitors based on the designed scaffold.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"14 ","pages":"3292"},"PeriodicalIF":5.1,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786929","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}