BMC Pharmacology & Toxicology最新文献

{"title":"Comparative analysis of safety and efficacy between brand and generic lamotrigine products in the Saudi market.","authors":"Haya Alotaibi, Sarah Sulaiman Alenazi, Sarah Alrubia, Maria Arafah, Nourah Alzoman, Aliyah Almomen","doi":"10.1186/s40360-025-00963-7","DOIUrl":"10.1186/s40360-025-00963-7","url":null,"abstract":"<p><strong>Background: </strong>Epilepsy is one of the most chronic neurological disorders worldwide. In 2023, the World Health Organization (WHO) estimates that approximately 50 million individuals globally would be affected by epilepsy. Furthermore, it was suggested that as many as 70% of patients could experience a life without seizure if they received appropriate treatment. Lamotrigine (LTG) is one of the newer antiepileptic drugs. It has been globally marketed under the name Lamictal^00AE. Due to the increasing demand for transformation between brand and generic products, this study aims to evaluate the product safety and efficacy on liver enzymes, as well as the behavioral effects and pharmacokinetics of lamotrigine, specifically the brand Lamictal^00AE and its generics available in the Saudi market.</p><p><strong>Methods: </strong>Male albino mice with an average weight of 24 g will be randomly divided into groups (n = 6) for pharmacokinetic study, liver enzyme analysis, and behavioral evaluation of brand Lamictal^00AE and generics. One-way ANOVA and Bonferroni's post hoc test will be used to compare results in the different animal groups. Statistical significance p-values will be determined at P < 0.05.</p><p><strong>Results: </strong>The study found that generics had a significant difference PK parameters were compared to those of Lamictal^00AE, which was mostly found in generics 1 and 2. Liver analysis revealed liver enzyme elevation in all generics compared to the brand Lamictal^00AE, which was primarily pronounced in AST and GGT with generic 2, and an increase in ALT, ALP, and GGT was primarily found in generic 1. The behavioral study indicates higher seizure attacks in generics compared to the brand Lamictal^00AE, with an increase in mortality rates mainly observed with generics 1 and 2.</p><p><strong>Conclusions: </strong>This research finds that there is a significant difference in safety and efficacy between brand and generic lamotrigine products in terms of liver enzyme tests, behavioral analysis, and PK parameters. Future studies to evaluate lamotrigine brand and generic drugs in humans are recommended.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"125"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of adverse event profiles for cefotaxime: a disproportionality analysis using the FDA adverse event reporting system.","authors":"Cheng Jiang, Jiancheng Qian, Yingyan Lu, Junxian Zheng","doi":"10.1186/s40360-025-00960-w","DOIUrl":"10.1186/s40360-025-00960-w","url":null,"abstract":"<p><strong>Background: </strong>Cefotaxime has been widely used in the clinical treatment of infections. However, there is still a lack of systematic researches for the adverse event profiles of cefotaxime through large-scale post-marketing monitoring.</p><p><strong>Methods: </strong>This study investigated the adverse event profiles for cefotaxime in the Food and Drug Administration Adverse Event Reporting System database, delving into clinical characteristics, adverse event signals and variations in these signals across subgroups.</p><p><strong>Results: </strong>Compared with Asia, Europe and America more commonly reported once-daily frequency. New severe hepatobiliary disorders were observed in neonates, children, or underweight elderly patients even when using adjusted doses below 1 g. Significant variations in adverse event signals were identified in relation to continent, dose, onset time, and outcome.</p><p><strong>Conclusions: </strong>The existence of non-recommended frequency in Europe and America warrants clinical attention when using cefotaxime. The identification of new severe hepatobiliary disorders highlights the critical need for personalized dosing strategies and intensified liver function monitoring for neonates, children, and elderly individuals with lower body weights. Furthermore, the differences in adverse event signals across subgroups underscore the necessity of developing targeted monitoring protocols. Further research is required to validate the association.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"129"},"PeriodicalIF":2.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determination of the latent geometry of atorvastatin pharmacokinetics by transfer entropy to identify bottlenecks.","authors":"Paola Lecca, Angela Re","doi":"10.1186/s40360-025-00948-6","DOIUrl":"10.1186/s40360-025-00948-6","url":null,"abstract":"<p><strong>Background: </strong>In mathematics, a physical network (e.g. biological network, social network, IT network, communication network) is usually represented by a graph. The determination of the metric space (also referred to as latent geometry) of the graph and the disposition of its nodes on it provide important information on the reaction propensity and consequently on the possible presence of bottlenecks in a system of interacting molecules, such as it happens in pharmacokinetics. To determine the latent geometry and the coordinates of nodes, it is necessary to have the dissimilarity or distance matrix of the network, an input that is not always easy to measure in experiments.</p><p><strong>Results: </strong>The main result of this study is the mathematical and computational procedure for determining the distance/dissimilarity matrix between nodes and for identifying the latent network geometry from experimental time series of node concentrations. Specifically, we show how this matrix can be calculated from the transfer entropy between nodes, which is a measure of the flow of information between nodes and thus indirectly of the reaction propensity between them. We implemented a procedure of spectral graph embedding to embed the distance/dissimilarity matrix in flat and curved metric spaces, and consequently to determine the optimal latent geometry of the network. The distances between nodes in the metric space describing the latent geometry can be analyzed to identify bottlenecks in the reaction system. As a case study for this procedure, we consider the pharmacokinetics of atorvastatin, as described by recent studies and experimental time data.</p><p><strong>Conclusions: </strong>The method of determining distances between nodes from temporal measurements of node concentrations through the calculation of transfer entropy makes it possible to incorporate the information of kinetics (inherent in the time series) in the construction of the distance/dissimilarity matrix, and, consequently, in the determination of the network latent geometry, a characterisation of the network itself that is intimately connected to its dynamics, but which has so far been scarcely investigated and taken into account. The results on the case study of the pharmacokinetics of atorvastatin corroborate the usability and reliability of the method within certain limits of the experimental errors on the data.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 Suppl 1","pages":"123"},"PeriodicalIF":2.8,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-treatment of β-carotene with acetamiprid provides protection against acetamiprid induced hepatic and renal toxicity via modulation of the antioxidant system.","authors":"Eatemad A Awadalla, Yahia A Amin, Rana A Ali, Samia A Gbr, Wafaa Ibraheem Gelany, Amna H M Nour","doi":"10.1186/s40360-025-00953-9","DOIUrl":"10.1186/s40360-025-00953-9","url":null,"abstract":"<p><strong>Background: </strong>Acetamiprid (ACMP), one of the most widely used and effective insecticides globally, can pose potential toxicity to mammals. β-carotene (βC) is a prominent carotenoid precursor to vitamin A and exhibits antioxidant properties. This study evaluated the protective effect of βC as an antioxidant against ACMP toxicity in rats.</p><p><strong>Methods: </strong>A total of 40 male albino rats were divided into four groups: the control group received 1% DMSO; the βC group received 100 mg/kg of β-carotene; the ACMP group received 40 mg/kg of acetamiprid; and the ACMP + βC group received both ACMP and βC. Liver and kidney tissues were used for biochemical analyses (total oxidative stress [TOS] and total antioxidant capacity [TAC]), as well as histopathological, histochemical, and immunohistochemical analyses (MPO immunostaining).</p><p><strong>Results: </strong>The ACMP group, compared to the control and βC groups, showed a significant increase in TOS levels (p < 0.001) in both liver and kidney tissue homogenates, along with a significant decrease in TAC in the same tissues. The ACMP + βC group exhibited significantly lower TOS levels (p < 0.01) and significantly higher TAC levels (p < 0.05) than the ACMP group in the liver and kidney tissue homogenates. Furthermore, histopathological alterations were observed in both organs. Changes such as congestion of central veins and blood sinusoids in the liver were noted. In most cases, hepatocytes exhibited basophilic cytoplasm, vacuolar cytoplasm, and pyknotic nuclei. Renal alterations included atrophy of the renal corpuscle, reduced glomerular cellularity, marked dilation of the urinary space, desquamated epithelial cells in the tubular lumen, inflammatory cell infiltration, and congestion of interstitial blood capillaries. In contrast, the ACMP + βC group showed significant improvements in these histopathological changes. MPO immunostaining revealed a significant increase in the ACMP group compared to the other three groups.</p><p><strong>Conclusion: </strong>Co-treatment with β-carotene and acetamiprid reduced ACMP-induced toxicity by enhancing antioxidant capacity and reducing oxidative stress.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"122"},"PeriodicalIF":2.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Naringin mitigated doxorubicin-induced kidney injury by the reduction of oxidative stress and inflammation with a synergistic anticancer effect.","authors":"Nahla S Gad, Sameh M Shabana, Maggie E Amer, Azza I Othman, Mohamed A El-Missiry","doi":"10.1186/s40360-025-00947-7","DOIUrl":"10.1186/s40360-025-00947-7","url":null,"abstract":"<p><strong>Background: </strong>The pathophysiology and severity of kidney impairment due to doxorubicin (DOX) treatment are markedly influenced by oxidative stress and inflammation. Naringin (NG), a natural flavonoid, has anti-inflammatory and antioxidant properties. The nephroprotective effect of NG on DOX-induced kidney toxicity was investigated to increase its utility in clinical settings.</p><p><strong>Methods: </strong>DOX toxicity was induced by a single ip injection (15 mg/kg) and for possible protection NG (100 mg/Kg) was used.</p><p><strong>Results: </strong>Kidney damage and dysfunction were indicated by an elevation in the levels of creatinine, urea, uric acid, and the activity of ALP and LDH in serum, KIM-1, and NAGAL in kidney, and a significant decrease in nephrin and podocin in renal tissue. These disrupted glomerular and tubular function indicators were remarkably ameliorated by oral administration of NG (100 mg/kg) daily for 10 days before DOX treatment and continued for an additional four days post-Dox treatment. The nephroprotective effect of NG was confirmed by the improvement of histopathological and PAS histochemical investigations. The mitigating impact of NG was verified by normalization of the redox balance, evidenced by a significant amelioration of ROS levels, oxidative stress markers (MDA, PC, 8-OHdG), and antioxidants (GSH, GPx, GR), as well as upregulation of Nrf2 expression in kidney. Furthermore, NG significantly prevented the increase in the inflammatory mediators (IL-6, IL-1β, TNF-α, and NF-κB) and upregulated the anti-inflammatory IL-10 in DOX-treated rats. The expression of TGF-β1 and the apoptotic protein caspase-3 in the kidneys significantly decreased as a result of the improvement in redox state in renal tissue. Additionally, NG demonstrated anticancer effects and their combination showed synergistic anticancer impact on larynx and colon cancer cell lines in vitro study.</p><p><strong>Conclusions: </strong>NG demonstrated remarkable protection of kidney against DOX treatment.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"121"},"PeriodicalIF":2.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nano-encapsulated ferulic acid in sesame protein isolate alleviates acrylamide-induced liver toxicity and genotoxicity in rats via oxidative stress and DNA damage modulation.","authors":"Hend A Essa, Elham Ali, Fatma El Zahraa Abd El Hakam, Engy M Akl","doi":"10.1186/s40360-025-00946-8","DOIUrl":"10.1186/s40360-025-00946-8","url":null,"abstract":"<p><strong>Background: </strong>Acrylamide (ACR) induces hepatotoxicity and genotoxicity through oxidative stress and inflammatory processes.</p><p><strong>Aims: </strong>This study explores the potential of ferulic acid encapsulated in sesame protein isolate (SPI) and its nanoform as a non-toxic, effective therapy for ACR-induced oxidative liver injury in rats.</p><p><strong>Methods: </strong>SPI was prepared from defatted sesame flour. SPI exposed to ultrasonic waves to obtain nano SPI, and then ferulic acid was added to form capsules. Fourier transforms infrared spectra, scaning electron microscope, and polarizing optical microscope were used in investigating functional groups and surface morphology of both encapsulations respectively. Rats were divided into four groups, each consisting of six animals: normal control, ACR-treated (20 mg/kg/day), sesame protein encapsulated ferulic acid-treated, and sesame protein nano-encapsulated ferulic acid-treated groups. Both encapsulated forms were administered daily in the diet alongside ACR for two weeks. Liver function indices, oxidative stress biomarkers, DNA fragmentation, comet assay, and histopathological and immunohistochemical examinations were performed.</p><p><strong>Results: </strong>The encapsulation efficiency of the nano-encapsulated form was higher than that of the other forms. Both encapsulated forms significantly improved liver function, elevated levels of GSH, GPx, SOD, and CAT were observed, along with decreased concentrations of MDA, interleukin-6, and tumor necrosis factor-α. The treatments also provided protection against DNA damage and genotoxicity, alleviated histological damage, and reduced liver toxicity and genotoxicity.</p><p><strong>Conclusion: </strong>Both encapsulated forms, especially the nanoform, significantly mitigated liver toxicity. These findings underscore their potential as effective natural therapies for liver damage caused by ACR, and supporting liver health.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"120"},"PeriodicalIF":2.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of adding fenofibrate versus curcumin to glimepiride in patients with type 2 diabetes: a randomized controlled trial.","authors":"Eman M Nada, Nashwa M El-Gharbawy, Haidy Abbas, Rehab H Werida","doi":"10.1186/s40360-025-00950-y","DOIUrl":"10.1186/s40360-025-00950-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Type 2 diabetes is a recognized risk factor for the development of cardiovascular disease. Fenofibrate and curcumin were found to be effective in improving hyperlipidemia in patients with diabetes. This study aimed to evaluate the effect of adding fenofibrate versus curcumin on weight, glycemic status, lipids profile, high-sensitivity C-reactive protein (hs-CRP), fetuin-A, and sirtuin 1 in patients with type 2 diabetes treated with glimepiride.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method: &lt;/strong&gt;In a double-blind, randomized control trial, 60 patients with type 2 diabetes mellitus were randomly assigned into three groups: Group I was given placebo; Group II curcumin 1100 mg; Group III fenofibrate 160 mg (each administered orally once daily) to ongoing glimepiride 4 mg therapy administered orally once daily for three months. Inclusion criteria were as follows: patients aged 35-70 years, those with uncontrolled type 2 diabetes, hyperlipidemia, and those treated with glimepiride 4 mg. Exclusion criteria were as follows: other types of diabetes, pregnancy, abnormal liver or kidney function tests, using other anti-diabetes medications, and non-adherence to medications. At baseline and after three months of intervention, anthropometric measurements were measured, and blood samples were collected for biochemical analysis of blood glucose, glycated hemoglobin (HbA1c), lipid profile, hs-CRP, fetuin-A, and sirtuin 1. Paired t-test and one-way ANOVA were used for normally distributed data. However, the Wilcoxon signed-rank and the Kruskal-Wallis tests were used to analyze non-normally distributed data.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Three months after the intervention, when the three groups were compared, no significant differences were found regarding weight, body mass index, fasting blood glucose, two-hour postprandial glucose (2 h-PPG), and HbA1c (p &gt; 0.05). Compared to placebo, significant decreases were observed in total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), very-low-density lipoprotein cholesterol (VLDL-C), coronary risk index (CRI), atherogenic index (AI), and hs-CRP and increasing sirtuin 1 in the fenofibrate (p &lt; 0.001) and curcumin (p &lt; 0.05) groups. High-density lipoprotein cholesterol (HDL-C) levels in the fenofibrate group were found to be significantly higher than in the placebo group (p &lt; 0.001). Furthermore, when compared to curcumin, fenofibrate significantly reduced waist circumferences and fetuin-A and increased sirtuin 1 (p &lt; 0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Both fenofibrate and curcumin are effective at decreasing lipid profiles and improving inflammatory markers in patients with type 2 diabetes. Fenofibrate might have a superior effect in reducing waist circumference, decreasing fetuin-A, and increasing sirtuin 1.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Trial registration: &lt;/strong&gt;This trial was registered (August 27, 2020) on clinical trial.","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"119"},"PeriodicalIF":2.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated network toxicology, machine learning and molecular docking reveal the mechanism of benzopyrene-induced periodontitis.","authors":"Wen Wenjie, Li Rui, Zhuo Pengpeng, Deng Chao, Zhang Donglin","doi":"10.1186/s40360-025-00961-9","DOIUrl":"10.1186/s40360-025-00961-9","url":null,"abstract":"<p><strong>Background: </strong>Environmental pollutants, particularly from air pollution and tobacco smoke, have emerged as significant risk factors. Benzopyrene (BaP), a Group 1 carcinogen, is ubiquitously present in these pollutants, yet its molecular mechanisms in periodontitis remain largely unexplored.</p><p><strong>Methods: </strong>We investigated these mechanisms through an integrated approach combining network toxicology, machine learning, and molecular docking analyses. Data from SwissTargetPrediction, CTD databases, and GEO datasets were analyzed to identify potential targets. Three machine learning algorithms (Support Vector Machine, Random Forest, and LASSO regression) were applied for core target identification, followed by Molecular docking analyses.</p><p><strong>Results: </strong>We identified 11 potential targets associated with BaP-induced periodontitis, primarily involved in cellular response to lipopolysaccharide, endoplasmic reticulum function, and cytokine activity, particularly in IL-17 and TNF signaling pathways. Machine learning analysis identified three core targets: CXCL12, CYP24A1, and HMGCR. Molecular docking demonstrated strong binding affinities between BaP and these targets (binding energies <-5.0 kcal/mol). A diagnostic nomogram based on these core targets achieved high prediction accuracy (AUC = 0.922).</p><p><strong>Conclusions: </strong>This first comprehensive analysis of BaP-induced periodontitis using an integrated computational approach elucidates potential molecular mechanisms and identifies specific therapeutic targets. The diagnostic nomogram developed offers a promising tool for clinical periodontitis risk assessment, providing new perspectives on understanding the impact of environmental pollutants on periodontal health.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"118"},"PeriodicalIF":2.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Comparative study on drug encapsulation and release kinetics in extracellular vesicles loaded with snake venom L - amino acid oxidase.","authors":"Divya Ramesh, Shankar M Bakkannavar, Vinutha R Bhat, K Sreedhara Ranganath Pai, Krishna Sharan","doi":"10.1186/s40360-025-00956-6","DOIUrl":"10.1186/s40360-025-00956-6","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"117"},"PeriodicalIF":2.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Silico drug evaluation by molecular docking, ADME studies and DFT calculations of 2-(6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)-N, N-dipropylacetamide.","authors":"Veysel Tahiroğlu, Kenan Gören, Mehmet Bağlan","doi":"10.1186/s40360-025-00958-4","DOIUrl":"10.1186/s40360-025-00958-4","url":null,"abstract":"<p><p>In this study, the structural, electronic, pharmacokinetic, and biological properties of molecule 2-(6-kloro-2-(4-klorofenil)imidazo[1,2-a]piridin-3-il)-N, N-dipropilasetamid (Alpidem), an imidazopyridine derivative anxiolytic known for its high BZ₁ (benzodiazepine-1) receptor affinity and low adverse effect profile, were comprehensively investigated by density functional theory (DFT) and in-silico methods. The alpidem molecule was optimized using the 6-311G(d, p) basis set with the B3LYP and B3PW91 methods; information on the stability and chemical reactivity of the structure was obtained via the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), molecular electrostatic potential (MEP) maps, natural bonding orbital (NBO) analysis, non-linear optical (NLO) properties, and Mulliken charge distributions. Comparative analysis of two different methods has shown that the results are consistent with each other and provide reliable data. In addition, the drug similarity, bioavailability score, bioactivity values, absorption, distribution, metabolism, and excretion (ADME) profiles of the Alpidem molecule were calculated, and it was determined that the Alpidem molecule has pharmacologically favorable properties. Within the scope of molecular docking analyses, its interactions with two different enzymes (PDB ID: 2Z5X and 4BDT) associated with Alzheimer's disease were evaluated. The binding energy values obtained were - 8.00 kcal/mol (2Z5X) and - 9.60 kcal/mol (4BDT), respectively, and the strong binding affinity, especially with the 4BDT protein, suggests that Alpidem may be a potential inhibitor candidate in Alzheimer's disease. This multi-level theoretical study demonstrates that Alpidem is a drug repurposing molecule not only as an anxiolytic but also in neurodegenerative diseases and provides important data that will shed light on experimental studies. The results of this multi-level theoretical study show that Alpidem is a drug repurposing molecule not only as an anxiolytic but also in neurodegenerative diseases and provides important data that will shed light on experimental studies.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"116"},"PeriodicalIF":2.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}