Current pharmaceutical design最新文献

{"title":"Investigation into the Mechanisms of Paeoniae Radix Rubra in the Treatment of Venous Thrombosis Using Network Pharmacology, Bioinformatics, and Molecular Docking Techniques.","authors":"Shuo Xu, Ajiao Hou, Jiaxu Zhang, Jinhao Xue, Shiwen Gao, Hai Jiang, Liu Yang","doi":"10.2174/0113816128374345250521115849","DOIUrl":"https://doi.org/10.2174/0113816128374345250521115849","url":null,"abstract":"<p><strong>Objective: </strong>This study investigates the potential targets and mechanisms of Paeoniae Radix Rubra (PRR) in treating Venous Thrombosis (VTE) by employing network pharmacology, bioinformatics analysis, and molecular docking validation.</p><p><strong>Methods: </strong>Active components of PRR were identified via TCMSP. VTE-related genes were screened from GEO datasets, and WGCNA analyzed key modules. A Protein-Protein Interaction (PPI) network was constructed using Cytoscape, followed by immune infiltration analysis. Core targets were functionally annotated via GO and KEGG pathways. Molecular docking and molecular dynamics simulations validated interactions between PRR components and core targets.</p><p><strong>Results: </strong>A total of 30 active components of PRR and 21 potential targets for the treatment of VTE were identified. From the PPI network, 10 hub genes were screened. KEGG pathway enrichment analysis demonstrated that the target genes were significantly enriched in pathways, such as the cGMP-PKG signaling pathway, B cell receptor signaling pathway, Th1 and Th2 cell differentiation, and IL-17 signaling pathway. Molecular docking results revealed that MAPK1, NFATC1, and SELP all had good affinity with the screened active components. Among them, MAPK1 and beta-sitosterol exhibited the highest binding energy of -8.73 kcal/mol.</p><p><strong>Conclusion: </strong>Through this study, it was found that PRR may act on targets, such as MAPK1 and NFATC1, through components like beta-sitosterol and Stigmasterol. Among them, the complex (beta-sitosterol - MAPK1) may be the key active component that plays a role in treating VTE.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends in 4D Printed Shape Memory Biomaterials for Tissue Engineering Applications.","authors":"Deepak Kumar, Rishabha Malviya, Sathvik Belagodu Sridhar, Tarun Wadhwa, Sirajunisa Talath, Javedh Shareef","doi":"10.2174/0113816128374450250502051929","DOIUrl":"https://doi.org/10.2174/0113816128374450250502051929","url":null,"abstract":"<p><p>Shape memory polymers and stimuli-sensitive materials are utilised in 4D printing to develop tissue structures that are dynamic and flexible. The capability of these polymers to react to numerous stimuli like pH, light, and temperature increases the adaptability and usefulness of tissue engineering applications. The article aims at the application of smart SMPs in 4D printing for tissue engineering, emphasising their response to diverse physical and chemical stimuli. The current review article compiled data from previously reported studies by searching in commonly used electronic databases such as Scopus, Google Scholar, PubMed, Science Direct, etc. The authors have preferably considered the data from the last 10 years for inclusion. The study addresses developments in smart shape memory polymers and their transformational influence on biological applications. The integrated approach of 4D printing and shape memory biomaterials can potentially improve tissue engineering applications. Researchers can enhance tissue regeneration by utilising the responsive properties of these materials to physiological signals. This allows for the design of dynamic scaffolds that closely imitate the behaviour of real tissue, resulting in more efficient tissue regeneration. 4D-printed shape memory biomaterials have the potential to enhance tissue engineering via the use of dynamic and adaptable scaffolds. However, some obstacles must be overcome, such as material limitations and the capacity to scale up production, to achieve successful clinical implementation.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Split-Mouth, Randomized, Double-Blind Clinical Trial of a Gelatin Hemostatic Dental Sponge Containing Aloe Vera Nanoparticles for Controlling Bleeding After Mandibular Posterior Teeth Extraction.","authors":"Amir Zandesh, Mahsa Mehrpouya, Paniz Panahi, Naiemeh Motallebi, Simin Sharifi, Solmaz Maleki Dizaj, Mohammad Ali Ghavimi","doi":"10.2174/0113816128363906250407111215","DOIUrl":"https://doi.org/10.2174/0113816128363906250407111215","url":null,"abstract":"<p><strong>Introduction: </strong>Hemostatic dental sponges are biodegradable materials and fast hemostats that can help blood clotting in the surgical site and quick repair of the dental surgery site. In this study, we investigated the bleeding control (blood absorption ability and active bleeding) of a hemostatic gelatin sponge containing aloe vera nanoparticles as a hemostatic material after the removal of mandibular posterior teeth in a doubleblind, randomized trial.</p><p><strong>Methods: </strong>A clinical trial was performed on 30 patients (13 males and 17 females) who were referred to the Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, for extraction of two mandibular molars. The plan was a split-mouth, randomized, double-blind clinical trial. To investigate the blood absorption ability of a hemostatic sponge containing aloe vera nanoparticles in each patient after tooth extraction, the sponge was placed in the socket of the extracted tooth. Sterile gauze was placed on the hemostat sponge containing aloe vera nanoparticles (test group). For the control group, the same process was repeated with a sponge without aloe vera nanoparticles. The number of used sterile gauzes was recorded and the mean excess blood weight was measured with a digital scale. Also, the amount of bleeding after 1 and 4 hours of tooth extraction was recorded for all patients as an active bleeding time.</p><p><strong>Results: </strong>The number of sterile gauzes used and the mean excess blood weight used in each group indicate blood absorption. The results showed that there was no significant difference in the amount of sterile gauze between the two groups (P=0.65). In both groups, the consumption of three sterile gauzes was the most frequent. However, the mean excess blood weight in the control group was significantly higher, which indicates the better efficiency of the test group (P=0.04). Besides, the examination of the patients showed that in none of the patients of the two groups, active bleeding was observed 1 and 4 hours after tooth extraction.</p><p><strong>Conclusion: </strong>The performance of the test sponge was better than the control sponge in controlling bleeding after tooth extraction. It seems that the obtained results cannot only be related to the presence of aloe vera nanoparticles. The differences in the bleeding control (blood absorption ability and the active bleeding time) for the used sponges can also influence the results. In addition, the use of aloe vera in the form of nanoparticles can contribute to early healing effects and other beneficial effects, such as antimicrobial effects in the toothextracted site.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Porphyrin-based MOFs for Gene Delivery in Cancer Therapy: Recent Advances and Progress.","authors":"Saina Kabiri, Rahmatollah Rahimi, M R Mozafari, Seyed Morteza Naghib","doi":"10.2174/0113816128359818250407020852","DOIUrl":"https://doi.org/10.2174/0113816128359818250407020852","url":null,"abstract":"<p><p>Cancer is one of the leading causes of death worldwide, which involves the uncontrolled growth of body cells. Cytotoxic chemotherapy drugs, such as tamoxifen, doxorubicin, methotrexate, and cisplatin, have shortcomings that have deprived these treatments of the desired efficiency to destroy tumor cells. Poor pharmacokinetics, severe side effects, and low targeting properties are examples of these shortcomings. Meanwhile, in the last few years, the use of nanocarriers in drug delivery systems has grown significantly. Porphyrins, also called life pigments, are classified as organic complexes. Due to their unique electrochemical and photophysical properties, they have been used in various fields, such as photodynamic therapy, fluorescence, and photoacoustic imaging. However, due to the limitations of these compounds in aqueous environments, such as aggregation by surface molecules, weak absorption in the biological spectral window, self-quenching, and poor chemical and optical stability, there are gaps in the clinical applications of porphyrins. To overcome these challenges, researchers have developed porphyrin-based MOFs. Metal-organic frameworks (MOFs), made of metal ions and clusters coupled with organic linkers, such as porphyrins, through self-assembly, retain the properties of porphyrins while offering additional advantages. Several synthetic approaches and significant advances have been made in the development of porphyrin-based MOFs, including combination therapies, advanced drug delivery, cancer therapy, and photodynamic therapy. Porphyrin-based metal-organic frameworks represent a transformative approach in cancer treatment by integrating multiple therapeutic functions, improving targeting mechanisms, ensuring safety, increasing drug delivery efficiency, and overcoming tumor biological barriers, such as hypoxia, and their day-to-day development promises the formation of more personalized and effective strategies.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association between Albumin, Globulin, Albumin-to-globulin Ratio, and Frailty in Middle-aged and Older Adults: Evidence from NHANES 2013-2014.","authors":"Lixin Sun, Cuie Li, Bin-Bin Feng, Yong-Yong Liu, Ruo-Wei Ma, Yu-Xuan Zhang, Guo-Cui Wu","doi":"10.2174/0113816128362350250423113437","DOIUrl":"https://doi.org/10.2174/0113816128362350250423113437","url":null,"abstract":"<p><strong>Aim: </strong>Inflammation and nutritional status have significant roles in frailty. While albumin and the albumin-to-globulin ratio (AGR) are recognized as inflammatory and nutritional biomarkers, and globulin is associated with inflammation, their relationships with frailty remain underexplored. This study explored the relationships between albumin, globulin, AGR, and frailty among middle-aged and older adults, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database.</p><p><strong>Methods: </strong>The study was a cross-sectional study with participants aged ≥45 years from the 2013-2014 NHANES database. The frailty assessment was based on a 36-item index of frailty constructed in NHANES, excluding nutritional indicators. The relationships between albumin, globulin, AGR, and frailty were analyzed using weighted multivariate regression analyses, smooth curve fitting, two-segment linear regression models, subgroup analyses, and interaction tests.</p><p><strong>Results: </strong>This study involved 1,506 middle-aged and older participants, with a frailty rate of 42.23%. Nonlinear relationships were identified between albumin, AGR, and frailty, while a linear relationship was observed between globulin and frailty. Two-segment linear regression models demonstrated that the inflection points for albumin and AGR were 3.90 and 1.91, respectively. On the left side of these inflection points, albumin and AGR were negatively associated with the prevalence of frailty. On the right side of these inflection points, albumin and AGR were not significantly associated with the prevalence of frailty.</p><p><strong>Conclusion: </strong>This study reveals two threshold effects on frailty in middle-aged and older adults: albumin and AGR. Below specific thresholds, both are linked to reduced frailty risk, but above these levels, neither shows a significant association. Globulin, however, consistently correlates with increased frailty. These findings highlight nonlinear relationships between albumin, AGR, and frailty, suggesting that maintaining optimal levels of these biomarkers may help prevent frailty.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mendelian Randomization Study on Serum Metabolites and Diabetic Nephropathy Risk: Identifying Potential Biomarkers for Early Intervention.","authors":"Siyuan Song, Jiangyi Yu","doi":"10.2174/0113816128377862250429045226","DOIUrl":"https://doi.org/10.2174/0113816128377862250429045226","url":null,"abstract":"<p><strong>Objective: </strong>In this study, the causation between serum metabolites and the risk of Diabetic Nephropathy (DN) was investigated by means of a Mendelian Randomization (MR) analysis.</p><p><strong>Method: </strong>Our data on diabetic nephropathy were obtained from the IEU OpenGWAS Project database, while serum metabolite data originated came from the GWAS summary statistics by Chen et al. The Inverse Variance Weighted (IVW) method was the main analysis approach, with Weighted Median (WME) and MREgger regression serving as supplementary approaches to construing the causalities between serum metabolites and the DN risk. In addition to the MR-Egger regression intercept, Cochran's Q test was utilized for sensitivity analysis, with P values used as the metric to assess the results.</p><p><strong>Results: </strong>In total, 14 SNPs regarding serum metabolites were chosen as Instrumental Variables (IVs). The IVW results indicated that levels of Behenoylcarnitine (C22), Arachidoylcarnitine (C20), and the ratio of 5-methylthioadenosine (MTA) to phosphate exerted a positive causal effect on the DN risk. Conversely, levels of 5-hydroxylysine, Butyrylglycine, 1-stearoyl-glycerophosphocholine (18:0), Isobutyrylglycine, 1-stearoyl-2- oleoyl-GPE (18:0/18:1), N2,N5-diacetylornithine, 2-butenoylglycine, 3-hydroxybutyroylglycine, N-acetylisoputreanine, the ratio of Arginine to Ornithine, and the ratio of Aspartate to Mannose exerted a negative impact of causality on the DN risk. By identifying these serum metabolites, high-risk patients can be recognized in the early stages of diabetic nephropathy, enabling preventive measures or delaying its progression. These findings also provide a solid foundation for further research into the underlying etiology of diabetic nephropathy.</p><p><strong>Conclusion: </strong>The translation of serum metabolites into clinical applications for DN aims to utilize changes in serum metabolites as biomarkers for early diagnosis, thereby monitoring the progression of DN and providing a foundation for personalized treatment. For instance, the development of serum metabolite diagnostic kits could be used for early detection and prevention of DN. Changes in metabolites can help identify different stages of DN.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the Potential of Gene Therapy for Duchenne Muscular Dystrophy.","authors":"Gyas Khan, Md Sadique Hussain","doi":"10.2174/0113816128386290250507101412","DOIUrl":"https://doi.org/10.2174/0113816128386290250507101412","url":null,"abstract":"<p><p>Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the DMD gene, leading to progressive muscle degeneration, loss of ambulation, cardiomyopathy, and early mortality. While advances in multidisciplinary care and pharmacological interventions, including corticosteroids and exon-skipping therapies, have improved patient outcomes, current treatments primarily provide symptomatic relief without addressing the underlying genetic defect. Gene therapy has emerged as a promising approach to modify disease progression, particularly through the use of adeno-associated virus (AAV)-mediated delivery of micro-dystrophin constructs. These truncated genes retain essential functional domains, enabling the restoration of dystrophin expression within the packaging limits of AAV vectors. Early-phase clinical trials have demonstrated encouraging safety profiles and transgene expression; however, challenges such as immune responses, variability in functional improvement, and long-term durability remain. Recent innovations, including optimized AAV capsids, immunomodulatory strategies, and genome editing technologies like CRISPR-Cas9, are actively being explored to overcome these barriers. Additionally, scalable vector manufacturing and the integration of real-world data are essential for broader clinical translation. This review synthesizes current advancements, clinical milestones, and future directions in gene therapy for DMD, emphasizing the need for precise dosing, long-term efficacy, and equitable access to fully realize the therapeutic potential of these evolving strategies.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Factors Influencing Cardiovascular Events and Mortality in Patients on Dialysis after Parathyroidectomy.","authors":"Taohong Yang, Yang Xue, Jianping Ren, XinYu Li, Wenting Xu, Guangyang Nie, Deguang Wang, Xuerong Wang","doi":"10.2174/0113816128390373250507062606","DOIUrl":"https://doi.org/10.2174/0113816128390373250507062606","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Renal secondary hyperparathyroidism (SHPT) represents a prevalent complication among dialysis patients, significantly impacting long-term prognosis. Parathyroidectomy (PTX) serves as a clinically effective therapeutic option for patients diagnosed with refractory secondary hyperparathyroidism.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aims to assess the impact of PTX on cardiovascular events (CVEs) and all-cause mortality in dialysis patients, as well as to analyze the incidence and potential determinants of postoperative cardiovascular events and all-cause mortality.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We collected data on 710 patients with renal secondary hyperparathyroidism who were treated with PTX between February 2011 and April 2019. A total of 633 patients who underwent PTX were finally included and matched with 462 patients who did not undergo PTX on a 1:1 basis according to age and follow-up duration. Ultimately, 179 pairs were successfully matched to investigate the differences in all-cause mortality and CVEs. The Logistic/Cox regression analyses were employed to identify independent factors associated with adverse CVEs and all-cause mortality among patients receiving PTX. Nomogram prediction models were constructed based on independent influencing factors.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among 633 patients who underwent PTX, 117 (18.5%) died and 192 (30.3%) experienced CVEs during median 5-year follow-up. No significant differences in cardiovascular/death events were observed between matched groups. In patients who underwent PTX, the logistic regression analysis revealed that age and history of diabetes mellitus were independent risk factors for CVEs. The pre-operative use of cinacalcet and/or calcitriol was associated with a reduced risk of CVEs. With respect to preoperative and postoperative calcium levels, the highest tertile was identified as a risk factor when compared with the lowest tertile. Cox regression showed age, diabetes history, and highest preoperative phosphorus tertile negatively correlated with survival, while albumin (ALB) was positively correlated. The predictive nomogram model had an area under the receiver operating characteristic (ROC) curve of 0.649 for CVE prediction. The areas under the ROC curve for predicting 3-, 5-, and 10-year mortality prediction were 0.865, 0.865, and 0.953, respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;PTX does not reduce the incidence of cardiovascular events and mortality in patients on maintenance dialysis. In patients who underwent PTX, older age, a history of diabetes mellitus, and higher preoperative calcium/postoperative calcium levels were independent risk factors for adverse CVEs; preoperative use of cinacalcet and/or calcitriol was a protective risk for CVEs. Older age, a history of diabetes mellitus, lower ALB levels, and hyperphosphatemia were independent risk factors for all-cause mortality following PTX. These predictive models may assist ","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence in Medicine and Imaging Applications.","authors":"Kuldeep Rajpoot","doi":"10.2174/0113816128381171250415171256","DOIUrl":"https://doi.org/10.2174/0113816128381171250415171256","url":null,"abstract":"<p><p>Artificial intelligence (AI) can completely transform drug development methods by delivering faster, more accurate, efficient results. However, the effective use of AI requires the accessibility of data of excellent quality, the resolution of ethical dilemmas, and an awareness of the drawbacks of AI-based techniques. Moreover, the application of AI in drug discovery is gaining popularity as an alternative to both the complex and time-consuming process of discovering as well as developing novel medications. Importantly, machine learning (ML) as well as natural language processing, for example, may boost both productivity as well as accuracy by analyzing vast volumes of data. This review article discusses in detail the promise of AI in drug discovery as well as offers insights into various topics such as societal issues related to the application of AI in medicine (e.g., legislation, interpretability and explainability, privacy and anonymity, and ethics and fairness), the importance of AI in the development of drug delivery systems, causability and explainability of AI in medicine, and opportunities and challenges for AI in clinical adoption, threat or opportunity of AI in medical imaging, the missing pieces of AI in medicine, approval of AI and ML-based medical devices.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Binding Interaction and Stability Analysis of Quercetin and its Derivatives as Potential Inhibitors of Triple Negative Breast Cancer (TNBC) against PARP1 Protein: An in-silico Study.","authors":"Md Alfaz Hossain, Fahmida Mariam Fariha, Md Arju Hossain, Md Reduanul Haque Kavey, Md Shamim, Md Mobinul Hoque, Ali Mohamod Wasaf Hasan, Md Ataur Rahman, Abdel Halim Harrath, Md Habibur Rahman","doi":"10.2174/0113816128373506250414160220","DOIUrl":"https://doi.org/10.2174/0113816128373506250414160220","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of estrogen and progesterone receptors (ER, PR) and low or absent HER2 expression, limiting treatment options. Quercetin, a flavonoid with anti-cancer properties, has the potential to be a therapeutic intervention.</p><p><strong>Objectives: </strong>The study aimed to explore the potential of Quercetin derivatives as therapeutic agents for TNBC using several computational methods.</p><p><strong>Methods: </strong>The study utilized PASS prediction, molecular docking, ADMET prediction, QSAR models, MD simulations, binding free energy, and DFT calculations to evaluate the efficacy of quercetin derivatives.</p><p><strong>Results: </strong>ADMET analysis confirmed the solubility, non-carcinogenicity, and low toxicity of four quercetin derivatives: LM01, LM02, LM05, and LM10. These derivatives exhibited strong binding affinity against TNBC protein PPAR1, with binding energies of -10.6, -10.7, -11.4, and -10 kcal/mol, respectively. MD simulations confirmed their stability, with consistent RMSD values and favorable RMSF values. Post-simulation calculations and reduced HOMO-LUMO energy gaps further supported their potential as promising candidates.</p><p><strong>Conclusion: </strong>Our computational findings suggest that quercetin derivatives, particularly LM01, LM02, and LM10, exhibit strong stability and binding affinity, positioning them as promising candidates for TNBC treatment. Further experimental validation is required to confirm their therapeutic potential.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062586","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}