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Recent Molecular Targets and their Ligands for the Treatment of Alzheimer Disease. 治疗阿尔茨海默病的最新分子靶点及其配体。
IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-01-01 DOI: 10.2174/0115680266318722240809050235
Gülşah Bayraktar, Vildan Alptüzün

Alzheimer's disease is a multifaceted neurodegenerative disease. Cholinergic dysfunction, amyloid β toxicity, tauopathies, oxidative stress, neuroinflammation are among the main pathologies of the disease. Ligands targeting more than one pathology, multi-target directed ligands, attract attention in the recent years to tackle Alzheimer's disease. In this review, we aimed to cover different biochemical pathways, that are revealed in recent years for the pathology of the disease, as druggable targets such as cannabinoid receptors, matrix metalloproteinases, histone deacetylase and various kinases including, glycogen synthase kinase-3, mitogen-activated protein kinase and c-Jun N-terminal kinase, and their ligands for the treatment of Alzheimer's disease in the hope of providing more realistic insights into the field.

阿尔茨海默病是一种多发性神经退行性疾病。胆碱能功能障碍、淀粉样蛋白 β毒性、陶氏病、氧化应激、神经炎症是该病的主要病理变化。近年来,针对一种以上病理机制的配体,即多靶点定向配体,在应对阿尔茨海默病方面备受关注。在这篇综述中,我们旨在介绍近年来揭示的可作为药物靶点的不同生化途径,如大麻素受体、基质金属蛋白酶、组蛋白去乙酰化酶和各种激酶(包括糖原合酶激酶-3、丝裂原活化蛋白激酶和 c-Jun N 端激酶),以及它们用于治疗阿尔茨海默病的配体,希望为这一领域提供更现实的见解。
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引用次数: 0
Effect of Withaferin-A, Withanone, and Caffeic Acid Phenethyl Ester on DNA Methyltransferases: Potential in Epigenetic Cancer Therapy. Withaferin-A、Withanone 和咖啡酸苯乙酯对 DNA 甲基转移酶的影响:表观遗传学癌症疗法的潜力。
IF 3.4 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-01-01 DOI: 10.2174/1568026623666230726105017
Vipul Kumar, Jaspreet Kaur Dhanjal, Anissa Nofita Sari, Mallika Khurana, Sunil C Kaul, Renu Wadhwa, Durai Sundar

Background: DNA methyltransferases (DNMTs) have been reported to be potential drug targets in various cancers. The major hurdle in inhibiting DNMTs is the lack of knowledge about different DNMTs and their role in the hypermethylation of gene promoters in cancer cells. Lack of information on specificity, stability, and higher toxicity of previously reported DNMT inhibitors is the major reason for inadequate epigenetic cancer therapy. DNMT1 and DNMT3A are the two DNMTs that are majorly overexpressed in cancers.

Objective: In this study, we have presented computational and experimental analyses of the potential of some natural compounds, withaferin A (Wi-A), withanone (Wi-N), and caffeic acid phenethyl ester (CAPE), as DNMT inhibitors, in comparison to sinefungin (SFG), a known dual inhibitor of DNMT1 and DNMT3A.

Methods: We used classical simulation methods, such as molecular docking and molecular dynamics simulations, to investigate the binding potential and properties of the test compounds with DNMT1 and DNMT3A. Cell culture-based assays were used to investigate the inactivation of DNMTs and the resulting hypomethylation of the p16INK4A promoter, a key tumour suppressor that is inactivated by hypermethylation in cancer cells, resulting in upregulation of its expression.

Results: Among the three test compounds (Wi-A, Wi-N, and CAPE), Wi-A showed the highest binding affinity to both DNMT1 and DNMT3A; CAPE showed the highest affinity to DNMT3A, and Wi-N showed a moderate affinity interaction with both. The binding energies of Wi-A and CAPE were further compared with SFG. Expression analysis of DNMTs showed no difference between control and treated cells. Cell viability and p16INK4A expression analysis showed a dose-dependent decrease in viability, an increase in p16INK4A, and a stronger effect of Wi-A compared to Wi-N and CAPE.

Conclusion: The study demonstrated the differential binding ability of Wi-A, Wi-N, and CAPE to DNMT1 and DNMT3A, which was associated with their inactivation, leading to hypomethylation and desilencing of the p16INK4A tumour suppressor in cancer cells. The test compounds, particularly Wi-A, have the potential for cancer therapy.

背景:据报道,DNA 甲基转移酶(DNMTs)是各种癌症的潜在药物靶点。抑制 DNMTs 的主要障碍是缺乏对不同 DNMTs 及其在癌细胞基因启动子超甲基化中作用的了解。缺乏有关特异性、稳定性和先前报道的 DNMT 抑制剂毒性较高的信息,是表观遗传癌症疗法不充分的主要原因。DNMT1和DNMT3A是癌症中主要过度表达的两种DNMT:在这项研究中,我们通过计算和实验分析了一些天然化合物(withaferin A (Wi-A)、withanone (Wi-N)和咖啡酸苯乙酯 (CAPE))作为 DNMT 抑制剂的潜力,并与已知的 DNMT1 和 DNMT3A 双重抑制剂正弦霉素 (SFG) 进行了比较:方法:我们采用分子对接和分子动力学模拟等经典模拟方法研究了测试化合物与 DNMT1 和 DNMT3A 的结合潜力和特性。利用基于细胞培养的实验研究了DNMTs的失活及其导致的p16INK4A启动子的低甲基化,p16INK4A是一种关键的肿瘤抑制因子,在癌细胞中因高甲基化而失活,导致其表达上调:在三种测试化合物(Wi-A、Wi-N和CAPE)中,Wi-A与DNMT1和DNMT3A的结合亲和力最高;CAPE与DNMT3A的结合亲和力最高;Wi-N与DNMT1和DNMT3A的结合亲和力中等。Wi-A 和 CAPE 的结合能与 SFG 进行了进一步比较。DNMTs的表达分析表明,对照细胞和处理过的细胞之间没有差异。细胞存活率和 p16INK4A 表达分析表明,与 Wi-N 和 CAPE 相比,Wi-A 会导致细胞存活率呈剂量依赖性下降,p16INK4A 会增加,而且 Wi-A 的作用更强:研究表明,Wi-A、Wi-N和CAPE与DNMT1和DNMT3A的结合能力不同,这与它们的失活有关,从而导致癌细胞中p16INK4A肿瘤抑制因子的低甲基化和去丝氨酸化。测试化合物,尤其是 Wi-A 具有治疗癌症的潜力。
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引用次数: 0
PIM Kinase Inhibitors as Novel Promising Therapeutic Scaffolds in Cancer Therapy. 将 PIM 激酶抑制剂作为癌症治疗的新型治疗支架。
IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-01-01 DOI: 10.2174/0115680266321659240906114742
Dipanjan Karati, Ankur Saha, Souvik Roy, Swarupananda Mukherjee

Cancer involves the uncontrolled, abnormal growth of cells and affects other tissues. Kinase has an impact on proliferating the cells and causing cancer. For the purpose of treating cancer, PIM kinase is a potential target. The pro-viral Integration site for moloney murine leukaemia virus (PIM) kinases is responsible for the tumorigenesis, by phosphorylating the proteins that control the cell cycle and cell proliferation. PIM-1, PIM-2, and PIM-3 are the three distinct isoforms of PIM kinases. The JAK/STAT pathway is essential for controlling how PIM genes are expressed. PIM kinase is also linked withPI3K/AKT/mTOR pathway in various types of cancers. The overexpression of PIM kinase will cause cancer. Currently, there are significant efforts being made in medication design and development to target its inhibition. A few small chemical inhibitors (E.g., SGI-1776, AZD1208, LGH447) that specifically target the PIM proteins' adenosine triphosphate (ATP)-binding domain have been identified. PIM kinase antagonists have a remarkable effect on different types of cancer. Despite conducting clinical trials on SGI-1776, the first PIM inhibitory agent, was prematurely withdrawn, making it unable to generate concept evidence. On the other hand, in recent years, it has aided in hastening the identification of multiple new PIM inhibitors. Cyanopyridines and Pyrazolo[1,5-a]pyrimidinecan act as potent PIM kinase inhibitors for cancer therapy. We explore the involvement of oncogenic transcription factor c-Mycandmi-RNA in relation to PIM kinase. In this article, we highlight the oncogenic effects, and structural insights into PIM kinase inhibitors for the treatment of cancer.

癌症涉及细胞不受控制的异常生长,并影响其他组织。激酶对细胞增殖和致癌有影响。为了治疗癌症,PIM 激酶是一个潜在的靶点。小鼠白血病病毒(PIM)激酶的亲病毒整合位点通过使控制细胞周期和细胞增殖的蛋白质磷酸化而导致肿瘤发生。PIM-1、PIM-2 和 PIM-3 是 PIM 激酶的三种不同异构体。JAK/STAT 通路对控制 PIM 基因的表达方式至关重要。在各种癌症中,PIM 激酶还与PI3K/AKT/mTOR 通路有关。PIM 激酶的过度表达会导致癌症。目前,针对抑制 PIM 激酶的药物设计和开发正在进行大量工作。目前已发现一些专门针对 PIM 蛋白的三磷酸腺苷(ATP)结合域的小型化学抑制剂(如 SGI-1776、AZD1208 和 LGH447)。PIM 激酶拮抗剂对不同类型的癌症有显著疗效。尽管第一种 PIM 抑制剂 SGI-1776 已进行了临床试验,但由于过早撤回,因此无法产生概念证据。另一方面,近年来,它又加速了多种新的 PIM 抑制剂的发现。氰基吡啶和吡唑并[1,5-a]嘧啶可作为有效的 PIM 激酶抑制剂用于癌症治疗。我们探讨了致癌转录因子 c-Mycandmi-RNA 与 PIM 激酶的关系。在本文中,我们重点介绍了 PIM 激酶的致癌作用,以及治疗癌症的 PIM 激酶抑制剂的结构见解。
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引用次数: 0
Combating COVID-19 Crisis using Artificial Intelligence (AI) Based Approach: Systematic Review. 利用基于人工智能(AI)的方法应对 COVID-19 危机:系统回顾。
IF 3.4 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-01-01 DOI: 10.2174/0115680266282179240124072121
Kavya Singh, Navjeet Kaur, Ashish Prabhu

Background: SARS-CoV-2, the unique coronavirus that causes COVID-19, has wreaked damage around the globe, with victims displaying a wide range of difficulties that have encouraged medical professionals to look for innovative technical solutions and therapeutic approaches. Artificial intelligence-based methods have contributed a significant part in tackling complicated issues, and some institutions have been quick to embrace and tailor these solutions in response to the COVID-19 pandemic's obstacles. Here, in this review article, we have covered a few DL techniques for COVID-19 detection and diagnosis, as well as ML techniques for COVID-19 identification, severity classification, vaccine and drug development, mortality rate prediction, contact tracing, risk assessment, and public distancing. This review illustrates the overall impact of AI/ML tools on tackling and managing the outbreak.

Purpose: The focus of this research was to undertake a thorough evaluation of the literature on the part of Artificial Intelligence (AI) as a complete and efficient solution in the battle against the COVID-19 epidemic in the domains of detection and diagnostics of disease, mortality prediction and vaccine as well as drug development.

Methods: A comprehensive exploration of PubMed, Web of Science, and Science Direct was conducted using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) regulations to find all possibly suitable papers conducted and made publicly available between December 1, 2019, and August 2023. COVID-19, along with AI-specific words, was used to create the query syntax.

Results: During the period covered by the search strategy, 961 articles were published and released online. Out of these, a total of 135 papers were chosen for additional investigation. Mortality rate prediction, early detection and diagnosis, vaccine as well as drug development, and lastly, incorporation of AI for supervising and controlling the COVID-19 pandemic were the four main topics focused entirely on AI applications used to tackle the COVID-19 crisis. Out of 135, 60 research papers focused on the detection and diagnosis of the COVID-19 pandemic. Next, 19 of the 135 studies applied a machine-learning approach for mortality rate prediction. Another 22 research publications emphasized the vaccine as well as drug development. Finally, the remaining studies were concentrated on controlling the COVID-19 pandemic by applying AI AI-based approach to it.

Conclusion: We compiled papers from the available COVID-19 literature that used AI-based methodologies to impart insights into various COVID-19 topics in this comprehensive study. Our results suggest crucial characteristics, data types, and COVID-19 tools that can aid in medical and translational research facilitation.

背景:SARS-CoV-2 是一种导致 COVID-19 的独特冠状病毒,它在全球范围内造成了破坏,受害者表现出各种各样的困难,这促使医疗专业人员寻找创新的技术解决方案和治疗方法。以人工智能为基础的方法在解决复杂问题方面做出了重要贡献,一些机构已迅速接受并定制了这些解决方案,以应对 COVID-19 大流行带来的障碍。在这篇综述文章中,我们介绍了一些用于 COVID-19 检测和诊断的 DL 技术,以及用于 COVID-19 识别、严重程度分类、疫苗和药物开发、死亡率预测、接触者追踪、风险评估和公众疏远的 ML 技术。本综述说明了人工智能/ML 工具对应对和管理疫情的整体影响。目的:本研究的重点是对人工智能(AI)作为应对 COVID-19 疫情的完整、高效解决方案的文献进行全面评估,涉及疾病检测和诊断、死亡率预测、疫苗和药物开发等领域:方法:采用PRISMA(系统综述和Meta分析首选报告项目)规定,对PubMed、Web of Science和Science Direct进行了全面探索,以找到2019年12月1日至2023年8月期间公开发表的所有可能合适的论文。COVID-19以及人工智能专用词被用来创建查询语法:在搜索策略覆盖的时间段内,共有 961 篇文章在网上发表和发布。其中,共有 135 篇论文被选中进行进一步调查。死亡率预测、早期检测和诊断、疫苗和药物开发,以及最后,将人工智能用于监督和控制 COVID-19 大流行,这四个主题完全集中在用于应对 COVID-19 危机的人工智能应用上。在 135 篇研究论文中,有 60 篇侧重于 COVID-19 大流行病的检测和诊断。其次,135 项研究中有 19 项采用了机器学习方法来预测死亡率。另有 22 篇研究论文强调了疫苗和药物的开发。最后,其余的研究集中于通过应用基于人工智能的 AI 方法来控制 COVID-19 大流行:在这项综合研究中,我们汇编了现有 COVID-19 文献中使用基于人工智能的方法对各种 COVID-19 主题进行深入研究的论文。我们的研究结果表明,COVID-19 的关键特征、数据类型和工具有助于医学研究和转化研究。
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引用次数: 0
Current Status of Hedgehog Signaling Inhibitors. 刺猬信号抑制剂的现状。
IF 3.4 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-01-01 DOI: 10.2174/0115680266280850231221074340
Xiaotang Wang, Tian Wang, Xiaona Song, Jiping Gao, Guoqiang Xu, Yunhui Ma, Guohua Song

The Hedgehog (Hh) signaling pathway plays a crucial role in diverse biological processes such as cell differentiation, proliferation, senescence, tumorigenesis, malignant transformation, and drug resistance. Aberrant Hh signaling, resulting from mutations and excessive activation, can contribute to the development of various diseases during different stages of biogenesis and development. Moreover, it has been linked to unfavorable outcomes in several human cancers, including basal cell carcinoma (BCC), multiple myeloma (MM), melanoma, and breast cancer. Hence, the presence of mutations and excessive activation of the Hh pathway presents obstacles and constraints in the realm of cancer treatment. Extant research has demonstrated that small molecule inhibitors are regarded as the most effective therapeutic approaches for targeting the Hh pathway in contrast to traditional chemotherapy and radiotherapy. Consequently, this review focuses on the present repertoire of small molecule inhibitors that target various components of the Hh pathway, including Hh ligands, Ptch receptors, Smo transmembrane proteins, and Gli nuclear transcription factors. This study provides a comprehensive analysis of small molecules' structural and functional aspects in the preclinical and clinical management of cancer. Additionally, it elucidates the obstacles encountered in targeting the Hh pathway for human cancer therapy and proposes potential therapeutic approaches.

刺猬(Hh)信号通路在细胞分化、增殖、衰老、肿瘤发生、恶性转化和耐药性等多种生物学过程中发挥着至关重要的作用。突变和过度作用导致的 Hh 信号转导异常可在生物生成和发育的不同阶段导致各种疾病的发生。此外,它还与基底细胞癌(BCC)、多发性骨髓瘤(MM)、黑色素瘤和乳腺癌等多种人类癌症的不良后果有关。因此,Hh 通路的突变和过度激活给癌症治疗带来了障碍和限制。现有研究表明,与传统的化疗和放疗相比,小分子抑制剂被认为是靶向 Hh 通路的最有效治疗方法。因此,本综述重点介绍了目前针对 Hh 通路各种成分的小分子抑制剂,包括 Hh 配体、Ptch 受体、Smo 跨膜蛋白和 Gli 核转录因子。本研究全面分析了小分子在癌症临床前和临床治疗中的结构和功能方面。此外,它还阐明了针对 Hh 通路进行人类癌症治疗所遇到的障碍,并提出了潜在的治疗方法。
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引用次数: 0
Physochlainae Radix: A Review of Ethnobotany, Phytochemistry, Pharmacology, Q-marker Prediction, and Future Directions. 药用植物:民族植物学、植物化学、药理学、Q 标记预测和未来方向综述。
IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-01-01 DOI: 10.2174/0115680266287982240517050139
Xin-Bo Zhang, Peiyuan Zhao, Yunlan Wang, Ying Zhang, Xuan Lei, Xiao Song

Background: Upon the release of the selection results of "Qin Medicine," numerous Chinese herbal medicines and proprietary Chinese medicines have regained attention. Physochlainae Radix (Huashanshen), a herbal medicine named after Mount Hua, the prominent peak in the Qinling Mountains, has garnered particular interest. Despite this, the impact of Physochlainae Radix and Qin medicines as a whole remains significantly overshadowed by the renown of Mount Hua.

Methods: Search on Using "Physochlainae Radix" as the keyword; searches were conducted across China National Knowledge Infrastructure (CNKI), Wanfang Data, WIP Database, PubMed, Web of Science, and the National Library of China databases.

Results: This study presents an overview of Physochlainae Radix by reviewing its history, chemical composition, preparation methods, planting and cultivation practices, concoctions, alkaloid detection, contraindications for use, resource recycling, and predicting quality markers.

Conclusion: To facilitate the further application and development of Physochlainae Radix, this study also addresses the challenges in the development of Qin medicines and proposes potential solutions.

背景:秦医》遴选结果公布后,众多中药材和中成药重新受到关注。其中,以秦岭主峰华山命名的 "华山参 "尤为引人关注。尽管如此,"华山 "的名气仍然远远盖过了 "秦药 "和 "秦药 "的影响力:以 "川贝母 "为关键词,在中国国家知识基础设施(CNKI)、万方数据、WIP 数据库、PubMed、Web of Science 和中国国家图书馆数据库中进行检索:本研究通过回顾其历史、化学成分、制备方法、种植和栽培方法、炮制方法、生物碱检测、使用禁忌、资源回收利用和质量指标预测等内容,概述了苏合香属植物:结论:为了促进秦艽的进一步应用和发展,本研究还探讨了秦药发展过程中面临的挑战,并提出了潜在的解决方案。
{"title":"<i>Physochlainae Radix</i>: A Review of Ethnobotany, Phytochemistry, Pharmacology, Q-marker Prediction, and Future Directions.","authors":"Xin-Bo Zhang, Peiyuan Zhao, Yunlan Wang, Ying Zhang, Xuan Lei, Xiao Song","doi":"10.2174/0115680266287982240517050139","DOIUrl":"10.2174/0115680266287982240517050139","url":null,"abstract":"<p><strong>Background: </strong>Upon the release of the selection results of \"Qin Medicine,\" numerous Chinese herbal medicines and proprietary Chinese medicines have regained attention. <i>Physochlainae Radix</i> (Huashanshen), a herbal medicine named after Mount Hua, the prominent peak in the Qinling Mountains, has garnered particular interest. Despite this, the impact of <i>Physochlainae Radix</i> and <i>Qin</i> medicines as a whole remains significantly overshadowed by the renown of Mount Hua.</p><p><strong>Methods: </strong>Search on Using \"<i>Physochlainae Radix</i>\" as the keyword; searches were conducted across China National Knowledge Infrastructure (CNKI), Wanfang Data, WIP Database, PubMed, Web of Science, and the National Library of China databases.</p><p><strong>Results: </strong>This study presents an overview of <i>Physochlainae Radix</i> by reviewing its history, chemical composition, preparation methods, planting and cultivation practices, concoctions, alkaloid detection, contraindications for use, resource recycling, and predicting quality markers.</p><p><strong>Conclusion: </strong>To facilitate the further application and development of <i>Physochlainae Radix</i>, this study also addresses the challenges in the development of Qin medicines and proposes potential solutions.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":"1856-1869"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455788","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
A Comprehensive Review on the Development of Titanium Complexes as Cytotoxic Agents. 全面回顾作为细胞毒剂的钛复合物的发展。
IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-01-01 DOI: 10.2174/0115680266317770240718080512
Nitesh Kumar, Raj Kaushal, Pamita Awasthi

After the discovery of cis-platin, the first metal-based anticancer drugs, budotitane, and titanocene dichloride entered clinical trials. These two classes of complexes were effective against those cell lines that are resistant to cis-platin and other platinum-based drugs. However, the main limitation of these complexes is their low hydrolytic stability. After these two classes, a third generation titanium based complex, i.e. diaminebis(phenolato)bis(alkoxo) titanium(IV), was invented, which showed more hydrolytic stability and high cytotoxicity than budotitane and titanocene dichloride. The Hydrolytic stability of complexes plays an important role in cytotoxicity. Earlier research showed that hydrolytically less stable complexes decompose rapidly into non-bioavailable moiety and become inactive. The mechanism of Ti(IV) complexes of diaminebis(phenolato) bis(alkoxo) is under investigation and is presumed to involve Endoplasmic Reticulum (ER) stress, which leads to apoptosis. The proposed mechanism involves the removal of ligands from the titanium complex and the binding of the Ti center to transferrin protein and its release inside the cell. Also, the structure of the ligand plays a key role in the cytotoxicity of complexes; as the bulkiness of the ligand increased, the cytotoxic nature of complexes decreased.

发现顺铂后,第一种金属基抗癌药物布多坦和二氯化钛进入了临床试验阶段。这两类复合物对顺式铂和其他铂类药物耐药的细胞株有效。然而,这些复合物的主要局限是水解稳定性低。在这两类络合物之后,人们发明了第三代钛基络合物,即二氨基双(苯酚)双烷氧基络合物,与布托替坦和二氯化钛相比,它具有更高的水解稳定性和更强的细胞毒性。络合物的水解稳定性在细胞毒性中起着重要作用。早期的研究表明,水解稳定性较差的络合物会迅速分解成不可生物利用的分子,从而失去活性。二氨基双(苯酚)双烷氧基钛(IV)络合物的作用机制正在研究之中,据推测可能涉及内质网(ER)应激,从而导致细胞凋亡。所提出的机制包括从钛复合物中去除配体,钛中心与转铁蛋白结合,并在细胞内释放。此外,配体的结构在复合物的细胞毒性中起着关键作用;随着配体体积的增加,复合物的细胞毒性也随之降低。
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引用次数: 0
Use of Olives-derived Phytochemicals for Prevention and Treatment of Atherosclerosis: An Update. 利用源自橄榄的植物化学物质预防和治疗动脉粥样硬化:最新进展。
IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-01-01 DOI: 10.2174/0115680266314560240806101445
Siarhei A Dabravolski, Elizaveta M Pleshko, Vasily N Sukhorukov, Victor Y Glanz, Igor A Sobenin, Alexander N Orekhov

Mediterranean diet is frequently associated with longevity and a lower incidence of adverse cardiovascular events because of the biological activities and health effects of olives - its key component. Olive oil, olive leaf extract, fruits and different by-products contain many bioactive components that exert anti-oxidant, anti-inflammatory and anti-apoptotic activities. In this review, we focus on the recent studies exploring molecular mechanisms underlying the cardioprotective properties of different olive oils, olive leave extracts, and specific micro-constituents (such as oleuropein, tyrosol, hydroxytyrosol and others) in vitro on rodent models and in clinical trials on human subjects. Particularly, hydroxytyrosol and oleuropein were identified as the major bioactive compounds responsible for the antioxidant, anti-inflammatory, anti-platelet aggregation and anti-atherogenic activities of olive oil. In total, the discussed results demonstrated a positive association between the consumption of olive oil and improvement in outcomes in atherosclerosis, diabetes, myocardial infarction, heart failure, hypertension and obesity.

地中海饮食经常与长寿和降低不良心血管事件的发生率联系在一起,这是因为其主要成分橄榄具有生物活性和保健作用。橄榄油、橄榄叶提取物、水果和不同的副产品含有许多生物活性成分,具有抗氧化、抗炎和抗细胞凋亡的作用。在这篇综述中,我们将重点介绍最近的一些研究,这些研究探索了不同橄榄油、橄榄叶提取物和特定微量成分(如油菜素、酪醇、羟基酪醇和其他成分)在体外啮齿动物模型和人体临床试验中保护心脏特性的分子机制。特别是羟基酪醇和油菜素被确定为橄榄油抗氧化、抗炎、抗血小板聚集和抗动脉粥样硬化活性的主要生物活性化合物。总之,所讨论的结果表明,食用橄榄油与改善动脉粥样硬化、糖尿病、心肌梗塞、心力衰竭、高血压和肥胖症的治疗效果之间存在积极的联系。
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引用次数: 0
The Role of Cytokines in Activation of Tumour-promoting Pathways and Emergence of Cancer Drug Resistance. 细胞因子在激活肿瘤促进途径和癌症抗药性出现中的作用
IF 3.4 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-01-01 DOI: 10.2174/0115680266284527240118041129
Ekta Shirbhate, Vaibhav Singh, Rakesh Kore, Subham Vishwakarma, Ravichandran Veerasamy, Amit K Tiwari, Harish Rajak

Scientists are constantly researching and launching potential chemotherapeutic agents as an irreplaceable weapon to fight the battle against cancer. Despite remarkable advancement over the past several decades to wipe out cancer through early diagnosis, proper prevention, and timely treatment, cancer is not ready to give up and leave the battleground. It continuously tries to find some other way to give a tough fight for its survival, either by escaping from the effect of chemotherapeutic drugs or utilising its own chemical messengers like cytokines to ensure resistance. Cytokines play a significant role in cancer cell growth and progression, and the present article highlights their substantial contribution to mechanisms of resistance toward therapeutic drugs. Multiple clinical studies have even described the importance of specific cytokines released from cancer cells as well as stromal cells in conferring resistance. Herein, we discuss the different mechanism behind drug resistance and the crosstalk between tumor development and cytokines release and their contribution to showing resistance towards chemotherapeutics. As a part of this review, different approaches to cytokines profile have been identified and employed to successfully target new evolving mechanisms of resistance and their possible treatment options.

科学家们不断研究和推出潜在的化疗药物,将其作为抗击癌症不可替代的武器。尽管过去几十年来,通过早期诊断、适当预防和及时治疗消灭癌症的工作取得了显著进展,但癌症并不准备放弃和离开战场。它不断试图寻找其他方法来为自己的生存打一场硬仗,要么逃避化疗药物的作用,要么利用自身的化学信使(如细胞因子)来确保抵抗力。细胞因子在癌细胞的生长和发展过程中扮演着重要角色,本文将重点介绍细胞因子在抗药性机制中的重要作用。多项临床研究甚至描述了癌细胞和基质细胞释放的特定细胞因子在产生抗药性方面的重要性。在此,我们将讨论耐药性背后的不同机制,以及肿瘤发生和细胞因子释放之间的相互影响及其对化疗药物产生耐药性的贡献。作为本综述的一部分,我们已经确定并采用了不同的细胞因子分析方法,以成功针对不断演变的新抗药性机制及其可能的治疗方案。
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引用次数: 0
Phytotherapeutics in Cancer: From Potential Drug Candidates to Clinical Translation. 癌症中的植物疗法:从潜在候选药物到临床转化。
IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-01-01 DOI: 10.2174/0115680266282518231231075311
Parul Grover, Kulbhushan Thakur, Monika Bhardwaj, Lovekesh Mehta, Soom Nath Raina, Vijay Rani Rajpal

Annually, a significant number of individuals succumb to cancer, an anomalous cellular condition characterized by uncontrolled cellular proliferation and the emergence of highly perilous tumors. Identifying underlying molecular mechanism(s) driving disease progression has led to various inventive therapeutic approaches, many of which are presently under pre-clinical and/or clinical trials. Over the recent years, numerous alternative strategies for addressing cancer have also been proposed and put into practice. This article delineates the modern therapeutic drugs employed in cancer treatment and their associated toxicity. Due to inherent drug toxicity associated with most modern treatments, demand rises for alternative therapies and phytochemicals with minimal side effects and proven efficacy against cancer. Analogs of taxol, Vinca alkaloids like vincristine and vinblastine, and podophyllotoxin represent a few illustrative examples in this context. The phytochemicals often work by modifying the activity of molecular pathways that are thought to be involved in the onset and progression of cancer. The principal objective of this study is to provide an overview of our current understanding regarding the pharmacologic effects and molecular targets of the active compounds found in natural products for cancer treatment and collate information about the recent advancements in this realm. The authors' interest in advancing the field of phytochemical research stems from both the potential of these compounds for use as drugs as well as their scientific validity. Accordingly, the significance of herbal formulations is underscored, shedding light on anticancer phytochemicals that are sought after at both pre-clinical and clinical levels, with discussion on the opportunities and challenges in pre-clinical and clinical cancer studies.

癌症是一种异常的细胞状态,其特点是细胞增殖失控和出现高度危险的肿瘤。通过识别驱动疾病进展的潜在分子机制,产生了各种创造性的治疗方法,其中许多方法目前正在进行临床前和/或临床试验。近年来,许多治疗癌症的替代策略也被提出并付诸实践。本文介绍了癌症治疗中使用的现代治疗药物及其相关毒性。由于大多数现代治疗方法都存在固有的药物毒性,因此对副作用小、疗效确切的替代疗法和植物化学物质的需求日益增加。紫杉醇的类似物、长春新碱和长春碱等长春花生物碱以及豆荚毒素就是这方面的几个典型例子。植物化学物质通常通过改变分子途径的活性来发挥作用,而这些分子途径被认为与癌症的发生和发展有关。本研究的主要目的是概述我们目前对天然产品中用于治疗癌症的活性化合物的药理作用和分子靶点的认识,并整理有关这一领域最新进展的信息。作者对推进植物化学研究领域的兴趣,既源于这些化合物作为药物使用的潜力,也源于它们的科学有效性。因此,作者强调了草药配方的重要性,揭示了在临床前和临床水平上都受到追捧的抗癌植物化学物质,并讨论了癌症临床前和临床研究中的机遇和挑战。
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Current topics in medicinal chemistry
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