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Screening of Herbs with Potential Modulation of NLRP3 Inflammasomes for Acute Liver Failure: A Study Based on the Herb-Compound-Target Network and the ssGSEA Algorithm. 筛选可能调节急性肝衰竭 NLRP3 炎症体的草药:基于草药-化合物-靶标网络和ssGSEA算法的研究
IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-11-08 DOI: 10.2174/0115680266331775241024064136
Haiya Ou, Susu Qiu, Xiaopeng Ye, Xiaotong Wang

Objective: NLRP3 inflammasomes are considered to be key factors in the pathogenesis of Acute Liver Failure (ALF). Some Traditional Chinese Medicines (TCMs) have shown protective and therapeutic effects against ALF by inhibiting NLRP3 inflammasomes. However, the inhibitory effects of most TCMs on ALF remain to be further elucidated. This study aimed to screen potential herbs that can treat ALF based on the inhibition of NLRP3 inflammasomes.

Methods: Initially, we constructed the target set for 502 herbs. Subsequently, based on the target set and the gene set related to the NLRP3 inflammasome, using the ssGSEA algorithm, we evaluated herb scores and NLRP3 scores in the ALF expression matrix and performed a preliminary herb screening based on score correlations. Through bioinformatics approaches, we identified the key targets for candidate herbs and determined core herbs based on the herb-compound-target network. Furthermore, molecular docking and molecular biology methods validated the screening results of the herbs.

Results: A total of 18 crucial targets associated with the inhibition of the NLRP3 inflammasome were identified, which included ALDH2, HMOX1, and VEGFA. Subsequently, based on these key targets, a set of 10 primary herbs was chosen, notably Qinghao, Duzhong, and Gouteng. Moreover, the results were verified through molecular docking and molecular dynamic simulation.

Conclusion: Ten key herbs have been identified as potential inhibitors of the NLRP3 inflammasome, offering insights into ALF therapy for drug development.

目的NLRP3炎性体被认为是急性肝衰竭(ALF)发病机制中的关键因素。一些中药通过抑制 NLRP3 炎性体对 ALF 具有保护和治疗作用。然而,大多数中药对 ALF 的抑制作用仍有待进一步阐明。本研究旨在基于对NLRP3炎性体的抑制作用,筛选治疗ALF的潜在中草药:方法:首先,我们构建了 502 种中草药的目标集。方法:首先,我们构建了 502 种中草药的靶向集;然后,基于靶向集和 NLRP3 炎症体相关基因集,利用 ssGSEA 算法评估了 ALF 表达矩阵中的中草药评分和 NLRP3 评分,并根据评分相关性进行了初步的中草药筛选。通过生物信息学方法,我们确定了候选药材的关键靶点,并根据药材-化合物-靶点网络确定了核心药材。此外,分子对接和分子生物学方法验证了药材筛选结果:结果:共发现了18个与抑制NLRP3炎性体相关的关键靶点,其中包括ALDH2、HMOX1和VEGFA。随后,根据这些关键靶点,选择了一组 10 味主药材,特别是秦艽、杜仲和钩藤。此外,还通过分子对接和分子动力学模拟对研究结果进行了验证:结论:十种主要中草药被确定为 NLRP3 炎症小体的潜在抑制剂,为 ALF 治疗的药物开发提供了启示。
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引用次数: 0
Computer-aided Drug Discovery of Epigenetic Modulators in Dual-target Therapy of Multifactorial Diseases. 多因素疾病双靶点治疗中表观遗传调节剂的计算机辅助药物发现。
IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-11-04 DOI: 10.2174/0115680266337668241025061804
Slavica Oljacic, Marija Popovic Nikolic, Brankica Filipic, Zarko Gagic, Katarina Nikolic

Numerous studies suggest that common genetic and epigenetic factors such as p53, histone deacetylase (HDAC), brain-derived neurotrophic factor (BDNF), the (Ataxia Telangiectasia mutated) ATM gene, cyclin-dependent kinase 5 (CDK5), glycogen synthase kinase 3 (GSK3) and altered expression of microRNA (miRNA) play a crucial role in cancer and neurodegeneration. As there is growing evidence that epigenetic aberrations in cancer and neurological diseases lead to complex pathophysiological changes, the simultaneous targeting of epigenetic and other related pathways by dual-target inhibitors may contribute to the discovery of more effective and personalized therapeutic options. Computer-Aided Drug Design (CADD) provides comprehensive bioinformatic, chemoinformatic, and chemometric approaches for the design of novel chemotypes of epigenetic dual-target inhibitors, enabling efficient discovery of new drug candidates for innovative treatments of these multifactorial diseases. The detailed anticancer mechanisms by which the epigenetic dual-target inhibitors alter metastatic and tumorigenic properties, influence the tumor microenvironment, or regulate the immune response are also presented and discussed in the review. To improve our understanding of the pathogenesis of cancer and neurodegeneration, this review discusses novel therapeutic agents targeting different molecular mechanisms involved in these multifactorial diseases.

大量研究表明,常见的遗传和表观遗传因素,如 p53、组蛋白去乙酰化酶(HDAC)、脑源性神经营养因子(BDNF)、(共济失调性远端神经病突变)ATM 基因、细胞周期蛋白依赖性激酶 5(CDK5)、糖原合酶激酶 3(GSK3)以及微 RNA(miRNA)表达的改变,在癌症和神经退行性疾病中起着至关重要的作用。越来越多的证据表明,癌症和神经系统疾病中的表观遗传畸变会导致复杂的病理生理变化,因此通过双靶点抑制剂同时靶向表观遗传和其他相关通路可能有助于发现更有效的个性化治疗方案。计算机辅助药物设计(CADD)为表观遗传双靶点抑制剂的新型化学型设计提供了全面的生物信息学、化学信息学和化学计量学方法,从而能够高效地发现新的候选药物,用于这些多因素疾病的创新治疗。综述还介绍并讨论了表观遗传双靶点抑制剂改变转移和致瘤特性、影响肿瘤微环境或调节免疫反应的详细抗癌机制。为了增进我们对癌症和神经变性发病机制的了解,本综述讨论了针对这些多因素疾病所涉及的不同分子机制的新型治疗药物。
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引用次数: 0
An Overview on Antifilarial Efficacy of Heterocyclic Motifs Encompassing Synthetic Strategies, SAR, and Commercialized Medications. 杂环基团的抗丝虫药效概述,包括合成策略、SAR 和商业化药物。
IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-11-01 DOI: 10.2174/0115680266321838241024073444
Sumit Tahlan, Sucheta Singh, Kailash C Pandey

Filariasis is one of the oldest, most dangerous, debilitating, disfiguring diseases and often ignores tropical disorders. It presents with a range of clinical symptoms, a low death rate, and a high morbidity rate, which contributes to social discrimination. This condition has major effects on people's socioeconomic circumstances. This illness is carried by mosquitoes that have spread malaria. Lymphatic filariasis, caused by Wuchereria bancrofti, Brugia malayi, and Brugia timori, is a crippling illness with serious social and economic consequences. The infection persisted despite therapy with conventional antifilarial medications such as diethylcarbamazine (DEC), albendazole, and ivermectin, which are mostly microfilaricides. Current treatments (ivermectin, diethylcarbamazine, and albendazole) have limited effectiveness against adult parasites and produce side effects; therefore, innovative antifilarial medications are urgently required. Hence, macrofilaricides, embryostatic agents, and improved microfilaricides are required. The following article discusses the typical synthetic methodologies established for antifilarial activity as well as their marketed pharmaceuticals, which will help researchers, medicinal chemists, and pharmaceutical scientists to develop new and effective antifilarial therapies. This review can help to identify new lead compounds and optimize existing commercial medications to improve their therapeutic efficacy. The majority of the studies addressed in this review concern the forms of filariasis, parasite life cycle, symptoms, medications used to treat filariasis, synthetic schemes, SAR, and results from the reported research.

丝虫病是最古老、最危险、最致残、最毁容的疾病之一,也是经常被忽视的热带疾病。它有一系列临床症状,死亡率低,发病率高,造成社会歧视。这种疾病对人们的社会经济状况有重大影响。这种疾病由传播疟疾的蚊子携带。淋巴丝虫病由班氏乌切瑞绦虫(Wuchereria bancrofti)、马来氏布鲁格绦虫(Brugia malayi)和蒂莫里氏布鲁格绦虫(Brugia timori)引起,是一种致残性疾病,具有严重的社会和经济后果。尽管使用了传统的抗丝虫药物(如乙酰甲胺嗪(DEC)、阿苯达唑和伊维菌素,这些药物主要是微丝蚴杀虫剂),但感染依然存在。目前的治疗方法(伊维菌素、乙酰甲胺嗪和阿苯达唑)对成虫的疗效有限,而且会产生副作用,因此迫切需要创新的抗丝虫药物。因此,需要大丝虫杀虫剂、胚胎抑制剂和改良的微丝杀虫剂。以下文章讨论了抗丝虫活性的典型合成方法及其上市药物,这将有助于研究人员、药物化学家和制药科学家开发新的、有效的抗丝虫疗法。这篇综述有助于确定新的先导化合物,并优化现有的商业药物以提高其疗效。本综述中涉及的大部分研究涉及丝虫病的形式、寄生虫的生命周期、症状、用于治疗丝虫病的药物、合成方案、SAR 以及报告的研究成果。
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引用次数: 0
Targeting c-Met in Cancer Therapy: Unravelling Structure-Activity Relationships and Docking Insights for Enhanced Anticancer Drug Design. 癌症治疗中的 c-Met 靶向:揭示结构-活性关系和对接洞察力,加强抗癌药物设计。
IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-10-31 DOI: 10.2174/0115680266331025241015084546
Surbhi Singh, Vaibhav Nigam, Shivani Kasana, Balak Das Kurmi, Ghanshyam Das Gupta, Preeti Patel

The c-Met receptor, a pivotal player in oncogenesis and tumor progression, has become a compelling target for anticancer drug development. This review explores the intricate landscape of Structure-Activity Relationship [SAR] studies and molecular binding analyses performed on c-Met inhibitors. Through a comprehensive examination of various chemical scaffolds and modifications, SAR investigations have elucidated critical molecular features essential for the potent inhibition of c-Met activity. Additionally, molecular docking studies have provided invaluable insights into how c-Met inhibitors interact with their target receptor, facilitating the rational design of novel compounds with enhanced efficacy and selectivity. This review highlights key findings from recent SAR and docking studies, particularly focusing on the structural determinants that govern inhibition potency and selectivity. Furthermore, the integration of computational methodologies with experimental approaches has accelerated the discovery and optimization of c-Met inhibitors, fostering the advancement of promising candidates for clinical applications. Overall, this review underscores the pivotal role of SAR and molecular docking studies in advancing our understanding of c-Met inhibition and guiding the rational design of next-generation anticancer agents targeting this pathway.

c-Met 受体在肿瘤发生和发展过程中起着关键作用,已成为抗癌药物开发的一个引人注目的靶点。本综述探讨了对 c-Met 抑制剂进行的结构-活性关系研究和分子结合分析的复杂情况。通过对各种化学支架和修饰的全面研究,SAR 研究阐明了有效抑制 c-Met 活性所必需的关键分子特征。此外,分子对接研究为了解 c-Met 抑制剂如何与其靶受体相互作用提供了宝贵的见解,有助于合理设计具有更强疗效和选择性的新型化合物。这篇综述重点介绍了近期 SAR 和对接研究的主要发现,尤其关注影响抑制效力和选择性的结构决定因素。此外,计算方法与实验方法的整合加快了 c-Met 抑制剂的发现和优化,促进了有希望的候选药物的临床应用。总之,这篇综述强调了 SAR 和分子对接研究在促进我们对 c-Met 抑制作用的理解以及指导针对这一途径的下一代抗癌药物的合理设计方面所起的关键作用。
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引用次数: 0
Triazole scaffold-based DPP-IV Inhibitors for the management of Type-II Diabetes Mellitus: Insight into Molecular Docking and SAR. 基于三唑支架的 DPP-IV 抑制剂用于治疗 II 型糖尿病:分子对接和 SAR 见解。
IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-10-31 DOI: 10.2174/0115680266339313241021053225
Saniya Shamim, Ozair Alam, Mukund Jha, Shagufi Nazar, Vishal Mathur, Shaheen Ali, Anam Iliyas, Kailash Chandra, Shaikh Mohd Aatif Jamil Ahmed, Mohd Javed Naim, Bushra Parveen

Diabetes mellitus, characterized as a chronic metabolic disorder or a polygenic syndrome; is increasing at a very fast pace among every group of the population worldwide. It arises due to the inability of the body to produce enough insulin (the hormone responsible for controlling blood sugar levels) or inability to utilize the insulin, leading to hyperglycaemic condition, which, if left uncontrolled gives rise to chronic microvascular and macrovascular complications like retinopathy, neuropathy, nephropathy, coronary artery disease, cognitive impairment, etc. Several therapeutic approaches are available for the treatment of diabetes; among which dipeptidyl peptidase (DPP-IV) inhibitors (gliptins) hold a significant place. DPP-IV is a multifunctional enzyme or a serine exopeptidase that plays an imperative role in cleaving bioactive molecules. DPP-IV causes the breakdown of incretin hormone (GLP-1: Glucagon-like peptide 1 and GIP: Glucose-dependent insulinotropic peptide) that is essential for controlling glycaemic levels in the body. Inhibition of DPP-IV enzyme (DPP-IV inhibitors: Sitagliptin, Saxagliptin, Linagliptin, Alogliptin) prevents this breakdown, thereby controlling blood glucose levels and saving the patients from deleterious effects of prolonged hyperglycaemic conditions. Triazole-based DPP-IV inhibitors are a significant class of drugs used to treat Type 2 diabetes mellitus in a dose-dependent manner. Clinical trials have demonstrated their efficacy as monotherapy or in combination with other antidiabetic agents. This review highlights the molecular docking studies and structure-activity relationship of potential synthetic derivatives that may act as lead molecules for future drug discovery and yield drug molecules with enhanced efficacy, potency and reduced toxicity profile.

糖尿病是一种慢性代谢紊乱或多基因综合征,在全球各个人群中的发病率都在快速上升。糖尿病是由于人体无法产生足够的胰岛素(负责控制血糖水平的激素)或无法利用胰岛素而导致的高血糖状态,如果不加以控制,会引起慢性微血管和大血管并发症,如视网膜病变、神经病变、肾病变、冠状动脉疾病、认知障碍等。目前有多种治疗糖尿病的方法,其中二肽基肽酶(DPP-IV)抑制剂(格列吡嗪)占有重要地位。DPP-IV 是一种多功能酶或丝氨酸外肽酶,在分解生物活性分子方面发挥着重要作用。DPP-IV 会导致增量素激素(GLP-1:胰高血糖素样肽 1 和 GIP:葡萄糖依赖性促胰岛素肽)的分解,而增量素激素对控制体内血糖水平至关重要。抑制 DPP-IV 酶(DPP-IV 抑制剂:西他列汀、沙格列汀、利纳列汀、阿格列汀)可防止这种分解,从而控制血糖水平,使患者免受长期高血糖的有害影响。三唑类 DPP-IV 抑制剂是以剂量依赖方式治疗 2 型糖尿病的一类重要药物。临床试验证明了它们作为单一疗法或与其他抗糖尿病药物联用的疗效。本综述重点介绍了潜在合成衍生物的分子对接研究和结构-活性关系,这些衍生物可能成为未来药物发现的先导分子,并产生具有更强疗效、效力和毒性特征的药物分子。
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引用次数: 0
An Insight into the Structure-Activity Relationship of Benzimidazole and Pyrazole Derivatives as Anticancer Agents. 苯并咪唑和吡唑衍生物作为抗癌剂的结构-活性关系透视。
IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-10-31 DOI: 10.2174/0115680266343336241021080438
Shital M Patil, Piyush Nikalje, Navnath Gavande, Kalyani D Asgaonkar, Vaishnavi Rathod

Introduction: Cancer is a leading cause of death worldwide, driving the urgent need for new and effective treatments. Benzimidazole and pyrazole derivatives have gained attention for their potential as anticancer agents due to their diverse biological activities. The development of resistance in cancer cells, toxicity concerns, and inconsistent efficacy across different types of cancer are a few of the challenges. To overcome these challenges, optimisation of these nuclei using the structure-activity relationships is necessary.

Objective: This review aimed to examine various benzimidazole, pyrazole, and their hybrid derivatives by focusing on their structure-activity relationships (SAR) as anticancer agents. Results of the most potent and least potent benzimidazole, pyrazole compounds, and their hybrid derivatives published by researchers were compiled.

Method: The findings of different researchers working on benzimidazole and pyrazole nuclei were reviewed and analysed for different targets and cell lines. Moreover, substitutions on different positions of pyrazole, benzimidazole, and their hybrid were summarised to derive an optimised pharmacophore.

Result: Based on our analysis of existing studies, we anticipate that this review will guide researchers in creating potent pyrazole, benzimidazole, and hybrid derivatives crucial for combating cancer effectively.

Conclusion: Structure-Activity Relationship (SAR) studies can help in developing pyrazolebenzimidazole hybrids that are more powerful and selective in targeting specific aspects of cancer.

简介癌症是导致全球死亡的主要原因,因此迫切需要新的有效治疗方法。苯并咪唑和吡唑衍生物具有多种生物活性,因此作为抗癌剂的潜力备受关注。但它们也面临着一些挑战,如癌细胞产生抗药性、毒性问题以及不同类型癌症的疗效不一致等。为了克服这些挑战,有必要利用结构-活性关系对这些核素进行优化:本综述旨在研究各种苯并咪唑、吡唑及其混合衍生物作为抗癌剂的结构-活性关系(SAR)。对研究人员发表的药效最强和药效最弱的苯并咪唑、吡唑化合物及其混合衍生物的研究结果进行了汇编:方法:针对不同的靶点和细胞系,对不同研究人员在苯并咪唑和吡唑核方面的研究成果进行了回顾和分析。此外,还总结了吡唑、苯并咪唑及其杂化物不同位置上的取代情况,以得出优化的药效谱:根据我们对现有研究的分析,我们预计本综述将指导研究人员创造出有效的吡唑、苯并咪唑和混合衍生物,这对有效抗击癌症至关重要:结论:结构-活性关系(SAR)研究有助于开发针对癌症特定方面更强、选择性更高的吡唑-苯并咪唑混合物。
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引用次数: 0
Hydroxamic Acids Derivatives: Greener Synthesis, Antiureolytic Properties And Potential Medicinal Chemistry Applications - A Concise Review. 羟肟酸衍生物:更绿色的合成、抗利尿特性和潜在的药物化学应用--简明综述。
IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-10-31 DOI: 10.2174/0115680266322401241021073138
Luciana P S Viana, Luan R Pinheiro, Lorenzo W Petrillo, Isabela G Medeiros, Tainá G Rizo, Luzia V Modolo, Cleiton M da Silva, Ângelo de Fátima

Hydroxamic acids (HAs) are chemical compounds characterized by the general structure RCONR'OH, where R and R' can denote hydrogen, aryl, or alkyl groups. Recognized for their exceptional chelating capabilities, HAs can form mono or bidentate complexes through oxygen and nitrogen atoms, rendering them remarkably versatile. These distinctive structural attributes have paved the way for a broad spectrum of medicinal applications for HAs, among which their pivotal role as inhibitors of essential Ni(II) and Zn(II)-containing metalloenzymes. In 1962, a significant breakthrough occurred when Kobashi and colleagues identified hydroxamic acids (HAs) as potent urease inhibitors. Subsequent research has increasingly underscored their capability in combatting infections induced by ureolytic microorganisms, including Helicobacter pylori and Proteus mirabilis. However, comprehensive reviews exploring their potential applications in treating infections caused by ureolytic microorganisms remain scarce in the scientific literature. Thus, this minireview aims to bridge this gap by offering a systematic exploration of the subject. Furthermore, it seeks to explore the significant advancements in obtaining hydroxamic acid derivatives through environmentally sustainable methodologies.

羟肟酸(HAs)是一种化合物,其一般结构为 RCONR'OH,其中 R 和 R'可表示氢、芳基或烷基。羟肟酸具有出色的螯合能力,可以通过氧原子和氮原子形成单齿或双齿络合物,因此用途非常广泛。这些与众不同的结构特性为 HAs 的广泛医药应用铺平了道路,其中 HAs 作为含 Ni(II)和 Zn(II)金属酶的重要抑制剂发挥了关键作用。1962 年,小桥及其同事发现羟肟酸 (HAs) 是一种有效的尿素酶抑制剂,这是一项重大突破。随后的研究越来越多地强调了羟肟酸在对抗幽门螺旋杆菌和奇异变形杆菌等尿素分解微生物诱导的感染方面的能力。然而,在科学文献中,探讨它们在治疗尿解微生物引起的感染中的潜在应用的全面综述仍然很少。因此,本微型综述旨在通过对这一主题的系统探讨来弥补这一空白。此外,它还试图探讨通过环境可持续方法获得羟肟酸衍生物的重大进展。
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引用次数: 0
Recent Advances in Amperometric Biosensors for Medical Applications: A Mini-Review. 用于医疗应用的安培生物传感器的最新进展:微型综述。
IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-10-28 DOI: 10.2174/0115680266323004241015122441
Anna S Kharkova, Lubov S Kuznetsova, Kristina D Ivanova, Maria M Gertsen, Vyacheslav A Arlyapov

Amperometric biosensors have emerged as a cutting-edge technology in clinical diagnostics, thanks to their high level of sensitivity, rapid analytical results, compact size, and ability to monitor health parameters non-invasively and continuously using flexible and wearable sensors. This review explores the latest developments in the field of amperometric biosensing for medical applications. It discusses the materials used to construct these sensors and pays particular attention to biosensors designed to measure glucose, lactate, cholesterol, urea, and uric acid levels. The review also addresses the technological limitations and drawbacks of these devices. Furthermore, it presents the current status and identifies future trends in the development of flexible, wearable biosensors capable of providing continuous monitoring of a patient's health status.

安培计生物传感器灵敏度高、分析速度快、体积小巧,并能利用灵活的可穿戴传感器对健康参数进行无创和连续监测,因此已成为临床诊断领域的尖端技术。本综述探讨了用于医疗应用的安培计生物传感领域的最新发展。它讨论了用于构建这些传感器的材料,并特别关注设计用于测量葡萄糖、乳酸盐、胆固醇、尿素和尿酸水平的生物传感器。该综述还讨论了这些设备的技术限制和缺点。此外,它还介绍了能够持续监测病人健康状况的柔性可穿戴生物传感器的发展现状,并指出了未来的发展趋势。
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引用次数: 0
Recent Advances in Multifaceted Drug Delivery Using Natural Polysaccharides and Polyacrylamide-Based Nanomaterials in Nanoformulation. 在纳米制剂中使用天然多糖和聚丙烯酰胺基纳米材料进行多元给药的最新进展。
IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-10-25 DOI: 10.2174/0115680266316522241015143856
Paromita Dutta Choudhury, Abu Md Ashif Ikbal, Sourav Saha, Rabin Debnath, Bikash Debnath, Loushambam Samananda Singh, Waikhom Somraj Singh

Rapid growth in nanotechnology, also known as 21st-century technology, is occurring in response to the increasing diversity of diseases. The development of safe and effective drug delivery methods to enhance bioavailability is of paramount importance. Researchers have focused on creating safe, cost-effective, and environmentally friendly nanoparticle construction processes. Natural polysaccharides, a type of multifaceted polymer with a wide range of applications and advantages, are particularly well suited for nanoparticle formulations, as they can mitigate the adverse consequences of synthetic nanoparticle formulations and promote sustainability. This review summarizes various sources of natural-based polysaccharides and polyacrylamide-based nanomaterials in nanoparticle preparation. Additionally, it discusses the use of natural polysaccharides in formulations beyond nanotechnology, highlighting their importance in green synthesis and different preparation methods.

纳米技术(又称 21 世纪技术)的迅速发展是为了应对日益多样化的疾病。开发安全有效的给药方法以提高生物利用率至关重要。研究人员一直致力于开发安全、经济、环保的纳米粒子制造工艺。天然多糖是一种具有广泛用途和优势的多元聚合物,尤其适合用于纳米粒子制剂,因为它们可以减轻合成纳米粒子制剂的不良后果,促进可持续发展。本综述概述了纳米粒子制备中天然多糖和聚丙烯酰胺基纳米材料的各种来源。此外,它还讨论了天然多糖在纳米技术以外的配方中的应用,强调了它们在绿色合成和不同制备方法中的重要性。
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引用次数: 0
ML-Based Models as a Strategy to Discover Novel Antiepileptic Drugs Targeting Sodium Receptor Channel. 将基于 ML 的模型作为发现靶向钠受体通道的新型抗癫痫药物的策略。
IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-10-22 DOI: 10.2174/0115680266331755241008061915
Priyanka Andola, Mukesh Doble

Background: Epilepsy remains the most common and chronic disorder demanding longterm management. The impact of epilepsy disease is a cause of great concern and has resulted in efforts to develop treatment for epilepsy. It occurs due to an increase in neuronal excitability produced by changes affecting the voltage-dependent properties of Voltage-gated Sodium Channels (VGSCs).

Materials and methods: Weka, a popular suite for machine learning techniques, was used on a dataset comprising 1781 chemical compounds, showing inhibition activity for sodium channel protein IX alpha subunit. After the analysis of the dataset obtained from ChEMBL, molecular fingerprints were computed for the molecules by the ChemDes server. Different classifiers available in the Weka software were explored to find out the algorithm that could be more suitable for the dataset or produce the highest accuracy for the classification of molecules as active or inactive.

Results: In this work, a comprehensive comparison of different classifiers in the Weka suite for the prediction of active, inactive, and intermediate classes of molecules showing inhibition against human NaV1.7 protein was made. The prediction accuracy of these classifiers was assessed based on performance measures, including accuracy, Root Mean Squared Error (RMSE), Receiver Operating Characteristic (ROC), precision, Mathews Correlation Coefficient (MCC), recall, and Fmeasure. The comparison of results for model performance demonstrated that the OneR classifier performed best over others when validated using percentage split, cross-validation, and supplied test methods. J48 and Bagging also performed equally well in the prediction of different classes with an MCC value of 1, ROC area equal to 1, and RMSE close to 0.

Conclusion: Machine Learning (ML) tools provide a fast, reliable, and cost-effective approach required to identify or predict inhibitory molecules for the treatment of a disease. This study shows that the ML methods, particularly OneR, J48, and Bagging have the ability to identify active and inactive classes of compounds for the human NaV1.7 protein target. Such predictive models may provide a reliable and time-saving approach that can aid in the design of potential inhibitors for the treatment of epilepsy disease.

背景:癫痫是最常见的慢性疾病,需要长期治疗。癫痫疾病的影响引起了人们的极大关注,并促使人们努力开发癫痫治疗方法。它的发生是由于影响电压门控钠通道(VGSCs)电压依赖特性的变化导致神经元兴奋性增加:Weka是一款流行的机器学习技术套件,用于分析由1781种化合物组成的数据集,这些化合物对钠离子通道蛋白IX alpha亚基具有抑制活性。在对从 ChEMBL 获取的数据集进行分析后,ChemDes 服务器计算出了分子的分子指纹。对 Weka 软件中的不同分类器进行了探索,以找出更适合该数据集的算法,或对分子进行活性或非活性分类的最高准确率:在这项工作中,对 Weka 套件中不同的分类器进行了综合比较,以预测对人类 NaV1.7 蛋白有抑制作用的分子的活性、非活性和中间类别。这些分类器的预测准确度是根据性能指标来评估的,包括准确度、均方根误差(RMSE)、接收者工作特征(ROC)、精确度、马修斯相关系数(MCC)、召回率和 Fmeasure。对模型性能的比较结果表明,在使用百分比分割、交叉验证和供应测试方法进行验证时,OneR 分类器的表现优于其他分类器。J48 和 Bagging 分类器在预测不同类别时表现同样出色,MCC 值为 1,ROC 面积等于 1,RMSE 接近 0.结论:机器学习(ML)工具为识别或预测治疗疾病的抑制性分子提供了一种快速、可靠且经济有效的方法。本研究表明,ML 方法,尤其是 OneR、J48 和 Bagging 能够识别人类 NaV1.7 蛋白靶点的活性和非活性化合物类别。这种预测模型可提供一种可靠、省时的方法,有助于设计治疗癫痫疾病的潜在抑制剂。
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Current topics in medicinal chemistry
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