Current pharmaceutical design最新文献

Homocysteine Blood Levels and Mandatory Folic Acid Fortification in Serbia. 塞尔维亚的同型半胱氨酸血药浓度和强制性叶酸强化剂。

IF 2.6 4区医学

Current pharmaceutical design Pub Date : 2024-10-03 DOI: 10.2174/0113816128326875240916050251

Zorana Vasiljevic, Natasa Zlatic, Dubravka Rajic, Predrag Mitrovic, Mihajlo Viduljevic, Dragan Matic, Milika Asanin, Sanja Stankovic

{"title":"Homocysteine Blood Levels and Mandatory Folic Acid Fortification in Serbia.","authors":"Zorana Vasiljevic, Natasa Zlatic, Dubravka Rajic, Predrag Mitrovic, Mihajlo Viduljevic, Dragan Matic, Milika Asanin, Sanja Stankovic","doi":"10.2174/0113816128326875240916050251","DOIUrl":"https://doi.org/10.2174/0113816128326875240916050251","url":null,"abstract":"Introduction/objective: The current study aims to investigate the blood Hcy levels in patients with CAD and hypertension in Serbia, a country with a high incidence and mortality of both diseases.Methods: The level of Hcy in the Serbian population was assessed in 123 patients with chronic coronary artery disease (CAD) and hypertension. There were 53 patients with chronic CAD and 70 patients with hypertension (HTA), but without CAD.Results: The Hcy levels were high in both groups of patients (the mean Hcy level of 16.0 ± 7.0 μmol/L) without a statistical difference between the patients in the CAD (14.9 ± 7.3 μmol/L) and hypertension (16.7 ± 6.7 μmol/L) groups. Hypercholesterolemia was found in 81% of the patients with CAD and 92.0% of the patients with HTA, as a common concern across both clinical conditions. It was also found that not a single conventional risk factor (diabetes, hypertension, the smoking status, the family history of CAD, and hyperlipidemia) may individually influence Hcy levels. By contrast, the low levels of vitamin B12 may be related to the high levels of Hcy.Conclusion: Given the fact that it is known that various factors interact and influence Hcy levels and associated cardiovascular risks, specific dietary habits, lifestyle and the other Serbia-specific possible factors were done.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Design of Novel Imidazole Derivatives as Potential Non-nucleoside Reverse Transcriptase Inhibitors Using Molecular Docking and Dynamics Strategies. 利用分子对接和动力学策略设计新型咪唑衍生物作为潜在的非核苷类逆转录酶抑制剂

IF 2.6 4区医学

Current pharmaceutical design Pub Date : 2024-10-01 DOI: 10.2174/0113816128322984240725055333

Priyanka Chandra, Swastika Ganguly, Pran Kishore Deb, Manik Ghosh

{"title":"Design of Novel Imidazole Derivatives as Potential Non-nucleoside Reverse Transcriptase Inhibitors Using Molecular Docking and Dynamics Strategies.","authors":"Priyanka Chandra, Swastika Ganguly, Pran Kishore Deb, Manik Ghosh","doi":"10.2174/0113816128322984240725055333","DOIUrl":"https://doi.org/10.2174/0113816128322984240725055333","url":null,"abstract":"Human Immunodeficiency Virus (HIV) has become an epidemic causing Acquired Immunodeficiency Syndrome (AIDS). Highly active antiretroviral therapy (HAART) consists of Nucleoside Reverse Transcriptase Inhibitors (NRTIS), Nucleotide Reverse Transcriptase Inhibitors (NtRTIS), and Non- Nucleoside Reverse Transcriptase Inhibitors (NNRTIS) with HIV Protease Inhibitors (HIV PIs). However, the emergence of resistant strains of NNRTIS necessitates the search for better HIV-1-RT inhibitors.Methods: In this study, a series of novel imidazoles (SP01-SP30) was designed using molecular docking inside the non-nucleoside inhibitory binding pocket (NNIBP) of the HIV-1-RT (PDB ID-1RT2) using Glide v13.0.137, Autodock Vina, and FlexX v2.1.3. Prime MMGBSA was used to study the free energy of binding of the inhibitors with the target enzyme. Molecular dynamics simulation studies were carried out to discover the dynamic behavior of the protein as well as to unveil the role of the essential amino acids required for the better binding affinity of the inhibitor within the NNIBP of the enzyme. The QikProp software module of Schrodinger and online SwissADME were also used to evaluate the drug-likeliness of these compounds.Results: The imidazole derivative SP08 is predicted to be the most promising design compound that can be considered for further synthetic exploitations to obtain a molecule with the highest therapeutic index against HIV-1-RT.Conclusion: The results of the current study demonstrate the robustness of our in-silico drug design strategy that can be used for the discovery of novel HIV-1-RT inhibitors.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Insight into Protein Engineering: From In silico Modelling to In vitro Synthesis. 洞察蛋白质工程：从硅学建模到体外合成。

IF 2.6 4区医学

Current pharmaceutical design Pub Date : 2024-10-01 DOI: 10.2174/0113816128349577240927071706

Anagha Balakrishnan, Saurav K Mishra, John J Georrge

{"title":"Insight into Protein Engineering: From In silico Modelling to In vitro Synthesis.","authors":"Anagha Balakrishnan, Saurav K Mishra, John J Georrge","doi":"10.2174/0113816128349577240927071706","DOIUrl":"https://doi.org/10.2174/0113816128349577240927071706","url":null,"abstract":"Protein engineering alters the polypeptide chain to obtain a novel protein with improved functional properties. This field constantly evolves with advanced in silico tools and techniques to design novel proteins and peptides. Rational incorporating mutations, unnatural amino acids, and post-translational modifications increases the applications of engineered proteins and peptides. It aids in developing drugs with maximum efficacy and minimum side effects. Currently, the engineering of peptides is gaining attention due to their high stability, binding specificity, less immunogenic, and reduced toxicity properties. Engineered peptides are potent candidates for drug development due to their high specificity and low cost of production compared with other biologics, including proteins and antibodies. Therefore, understanding the current perception of designing and engineering peptides with the help of currently available in silico tools is crucial. This review extensively studies various in silico tools available for protein engineering in the prospect of designing peptides as therapeutics, followed by in vitro aspects. Moreover, a discussion on the chemical synthesis and purification of peptides, a case study, and challenges are also incorporated.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An Updated Review Summarizing the Pharmaceutical Efficacy of Genistein and its Nanoformulations in Ovarian Carcinoma. 最新综述总结了染料木素及其纳米制剂对卵巢癌的药效。

IF 2.6 4区医学

Current pharmaceutical design Pub Date : 2024-10-01 DOI: 10.2174/0113816128332618240823044548

Pratibha Pandey, Seema Ramniwas, Shivam Pandey, Meenakshi Verma, Rahul Kumar, Sorabh Lakhanpal, Fahad Khan, Mohd Asif Shah

{"title":"An Updated Review Summarizing the Pharmaceutical Efficacy of Genistein and its Nanoformulations in Ovarian Carcinoma.","authors":"Pratibha Pandey, Seema Ramniwas, Shivam Pandey, Meenakshi Verma, Rahul Kumar, Sorabh Lakhanpal, Fahad Khan, Mohd Asif Shah","doi":"10.2174/0113816128332618240823044548","DOIUrl":"https://doi.org/10.2174/0113816128332618240823044548","url":null,"abstract":"Implementing lifestyle interventions as a primary prevention strategy is a cost-effective approach to reducing the occurrence of cancer, which is a significant contributor to illness and death globally. Recent advanced studies have uncovered the crucial role of nutrients in safeguarding women's health and preventing disorders. Genistein is an abundant isoflavonoid found in soybeans. Genistein functions as a chemotherapeutic drug against various forms of cancer, primarily by modifying apoptosis, the cell cycle, and angiogenesis and suppressing metastasis. Furthermore, Genistein has demonstrated diverse outcomes in women, contingent upon their physiological characteristics, such as being in the early or postmenopausal stages. The primary categories of gynecologic cancers are cervical, ovarian, uterine, vaginal, and vulvar cancers. Understanding the precise mechanism by which Genistein acts on ovarian cancer could contribute to the advancement of anti-breast cancer treatments, particularly in situations where no specific targeted therapies are currently known or accessible. Additional investigation into the molecular action of Genistein has the potential to facilitate the development of a plant-derived cancer medication that has fewer harmful effects. This research could also help overcome drug resistance and prevent the occurrence of ovarian cancers.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Camel FGF21 Protein Enhances FGF21 Signaling and its Targeted Compounds Screening. 骆驼 FGF21 蛋白增强 FGF21 信号转导及其靶向化合物筛选

IF 2.6 4区医学

Current pharmaceutical design Pub Date : 2024-09-30 DOI: 10.2174/0113816128332755240912041051

Yuan Gao, Fang Yong, Wangye Ji, Lili Zhang, Jibao Hou, Ruilin Ma, Shuqin Zhao, Huizhen Ge, Xiaoyu Wu

{"title":"Camel FGF21 Protein Enhances FGF21 Signaling and its Targeted Compounds Screening.","authors":"Yuan Gao, Fang Yong, Wangye Ji, Lili Zhang, Jibao Hou, Ruilin Ma, Shuqin Zhao, Huizhen Ge, Xiaoyu Wu","doi":"10.2174/0113816128332755240912041051","DOIUrl":"https://doi.org/10.2174/0113816128332755240912041051","url":null,"abstract":"Introduction: The hormone Fibroblast Growth Factor 21 (FGF21), as a novel glucose and lipid metabolism regulator, has become a promising therapeutic target for metabolic disorders. Camel, the characteristic species adapted to arid and semi-arid desert climates, has shown exceptional ability for the regulation of lipid reserve and utilization.Methods: This study found camel FGF21 to have a stronger regulatory effect for downstream signaling compared to human and mouse through sequence analysis and FGF21 signal downstream markers detection. FGF21 protein has been found to have one potential drug-binding pocket, which has been predicted using the CavityPlus online platform. Four small compounds, resorcinol monoacetate, tropisetron, nylidrin, and stiripentol, targeting FGF21 protein have been screened by molecular docking using the UCSF DOCK6 program.Results: The inhibitory concentration 50% (IC50) values of the four small compounds have been determined by MTT assay and the values have been simulated by the software GraphPad Prism. The biological effect testing has indicated the four compounds to be involved in the regulation of the FGF21 signaling pathway and serve as agonists for FGF21 signaling transduction. While the blocking experiment of compound and protein cotreatment has indicated the four small compounds to not inhibit FGF21-induced pathway activation. Even, resorcinol monoacetate and stiripentol have shown to synergistically activate downstream signaling pathways with the FGF21 protein.Conclusion: This study has provided new ideas for developing therapeutic strategies based on FGF21 protein modification and exploring novel disease treatment strategies based on the compounds-protein combination.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retinoic Acid Improves Vascular Endothelial Dysfunction by Inhibiting PI3K/AKT/YAP-Mediated Ferroptosis in Diabetes Mellitus. 维甲酸通过抑制 PI3K/AKT/YAP 介导的糖尿病铁蜕变改善血管内皮功能障碍

IF 2.6 4区医学

Current pharmaceutical design Pub Date : 2024-09-27 DOI: 10.2174/0113816128313964240728155100

Man Zhang, Yun Liu, Yu Liu, Bailin Tang, Hongxin Wang, Meili Lu

{"title":"Retinoic Acid Improves Vascular Endothelial Dysfunction by Inhibiting PI3K/AKT/YAP-Mediated Ferroptosis in Diabetes Mellitus.","authors":"Man Zhang, Yun Liu, Yu Liu, Bailin Tang, Hongxin Wang, Meili Lu","doi":"10.2174/0113816128313964240728155100","DOIUrl":"https://doi.org/10.2174/0113816128313964240728155100","url":null,"abstract":"Background: Vascular endothelial dysfunction is the initial factor involved in cardiovascular injury in patients with diabetes. Retinoic acid is involved in improving vascular complications in patients with diabetes, but its protective mechanism is still unclear. This study aimed to evaluate the effect and mechanism of All-Trans Retinoic Acid (ATRA) on endothelial dysfunction induced by diabetes.Methods: In the present study, streptozotocin (STZ)-induced diabetic rats and high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs) were observed, and the effects of ATRA on HG-induced endothelial dysfunction and ferroptosis were evaluated.Results: ATRA treatment improved impaired vasorelaxation in diabetic aortas in an endothelium-dependent manner, and this effect was accompanied by an increase in the NO concentration and eNOS expression. Ferroptosis, characterized by lipid peroxidation and iron overload induced by HG, was improved by ATRA administration, and a ferroptosis inhibitor (ferrostatin-1, Fer-1) improved endothelial function to a similar extent as ATRA. In addition, the inactivation of phosphoinositol-3-kinase (PI3K)/protein kinases B (AKT) and Yes-Associated Protein (YAP) nuclear localization induced by HG were reversed by ATRA administration. Vascular ring relaxation experiments showed that PI3K/AKT activation and YAP inhibition had similar effects on ferroptosis and endothelial function. However, the vasodilative effect of retinoic acid was affected by PI3K/AKT inhibition, and the inhibitory effects of ATRA on ferroptosis and the improvement of endothelial function were dependent on the retinoic acid receptor.Conclusion: ATRA could improve vascular endothelial dysfunction by inhibiting PI3K/AKT/YAP-mediated ferroptosis induced by HG, which provides a new idea for the treatment of vascular lesions in diabetes.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Herbal Remedies for Hepatic Inflammation: Unravelling Pathways and Mechanisms for Therapeutic Intervention. 治疗肝脏炎症的草药：揭示治疗干预的途径和机制。

IF 2.6 4区医学

Current pharmaceutical design Pub Date : 2024-09-27 DOI: 10.2174/0113816128348771240925100639

Istuti Saraswat, Anjana Goel

引用次数: 0

Advancing Pharmaceutical Science with Artificial Neural Networks: A Review on Optimizing Drug Delivery Systems Formulation. 利用人工神经网络推进制药科学：优化给药系统配方综述》。

IF 2.6 4区医学

Current pharmaceutical design Pub Date : 2024-09-26 DOI: 10.2174/0113816128301129240911064028

Simin Salarpour, Soodeh Salarpour, Mehdi Ansari Dogaheh

{"title":"Advancing Pharmaceutical Science with Artificial Neural Networks: A Review on Optimizing Drug Delivery Systems Formulation.","authors":"Simin Salarpour, Soodeh Salarpour, Mehdi Ansari Dogaheh","doi":"10.2174/0113816128301129240911064028","DOIUrl":"https://doi.org/10.2174/0113816128301129240911064028","url":null,"abstract":"Drug Delivery Systems (DDS) have been developed to address the challenges associated with traditional drug delivery methods. These DDS aim to improve drug administration, enhance patient compliance, reduce side effects, and optimize target therapy. To achieve these goals, it is crucial to design DDS with optimal performance characteristics. The final properties of a DDS are determined by several factors that go into formulating a pharmaceutical preparation. Thus, optimizing these factors can lead to the ideal DDS formulation. Artificial Neural Networks (ANN) are computational models that mimic the function of biological neurons and neural networks and perform mathematical operations on inputs to generate outputs. ANN is widely used in medical sciences for modeling disease diagnosis and treatment, dose adjustment in combination therapy, medical education, and other fields. In the pharmaceutical sciences, ANN has gained significant attention for designing and optimizing pharmaceutical formulations. This article reviews the use of ANN in the design and optimization of pharmaceutical formulations, specifically DDS. Since DDS is highly diverse, different factors are examined for each type of DDS. These factors are considered independent and dependent parameters for each ANN model, and various examples are provided. By utilizing ANN, it is possible to establish the relationship between the formulation factors and the resulting DDS characteristics, ultimately leading to the development of optimized DDS.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recent Advances in the Management of Malignant Melanoma. 恶性黑色素瘤治疗的最新进展。

IF 2.6 4区医学

Current pharmaceutical design Pub Date : 2024-09-26 DOI: 10.2174/0113816128342395240924093413

Marcio F Chedid, Jane Mattei

引用次数: 0

Lipid-based Non-viral Vector: Promising Approach for Gene Delivery. 脂质非病毒载体：有望实现基因传递的方法

IF 2.6 4区医学

Current pharmaceutical design Pub Date : 2024-09-24 DOI: 10.2174/0113816128324084240828084904

Anupama Panday, Bhupendra Dixena, Nishant Jain, Akhlesh Kumar Jain

{"title":"Lipid-based Non-viral Vector: Promising Approach for Gene Delivery.","authors":"Anupama Panday, Bhupendra Dixena, Nishant Jain, Akhlesh Kumar Jain","doi":"10.2174/0113816128324084240828084904","DOIUrl":"https://doi.org/10.2174/0113816128324084240828084904","url":null,"abstract":"Objectives: The present review aims to discuss various strategies to overcome intracellular and extracellular barriers involved in gene delivery as well as the advantages, challenges, and mechanisms of gene delivery using non-viral vectors. Additionally, patents, clinical studies, and various formulation approaches related to lipid-based carrier systems are discussed.Methods: Data were searched and collected from Google Scholar, ScienceDirect, Pubmed, and Springer.Results: In this review, we have investigated the advantages of non-viral vectors over viral vectors. The advantage of using non-viral vectors are that they seek more attention in different fields. They play an important role in delivering the genetic materials. However, few nonviral vector-based carrier systems have been found in clinical settings. Challenges are developing more stable, site-specific gene delivery and conducting thorough safety assessments to minimize the undesired effects.Conclusion: In comparison to viral vectors, nonviral vector-based lipid nanocarriers have more advantages for gene delivery. Gene therapy research shows promise in addressing health concerns. Lipid-based nanocarriers can overcome intracellular and extracellular barriers, allowing efficient delivery of genetic materials. Non-viral vectors are more attractive due to their biocompatibility, ease of synthesis, and cost-effectiveness. They can deliver various nucleic acids and have improved gene delivery efficacy by avoiding degradation steps. Despite limited clinical use, many patents have been filed for mRNA vaccine delivery using non-viral vectors.","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0