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Recent Advances in Nanocatalyzed One-Pot Sustainable Synthesis of Bioactive N, N-Heterocycles with Anticancer Activities: An Outlook of Medicinal Chemistry. 纳米催化一锅可持续合成具有抗癌活性的生物活性 N, N-杂环的最新进展:药物化学展望》。
IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-09-02 DOI: 10.2174/0115680266311149240822111827
Sasadhar Majhi

N-heterocycles represent a predominant and unique class of organic chemistry. They have received a lot of attention due to their important chemical, biomedical, and industrial uses. Food and Drug Administration (FDA) approved about 75% of drugs containing N-based heterocycles, which are currently available in the market. N-Heterocyclic compounds exist as the backbone of numerous natural products and act as crucial intermediates for the construction of pharmaceuticals, veterinary items, and agrochemicals frequently. Among N-based heterocyclic compounds, bioactive N,N-heterocycles constitute a broad spectrum of applications in modern drug discovery and development processes. Cefozopran (antibiotic), omeprazole (antiulcer), enviradine (antiviral), liarozole (anticancer), etc., are important drugs containing N,N-heterocycles. The synthesis of N,Nheterocyclic compounds under sustainable conditions is one of the most active fields because of their significant physiological and biological properties as well as synthetic utility. Current research is demanding the development of greener, cheaper, and milder protocols for the synthesis of N,N-heterocyclic compounds to save mother nature by avoiding toxic metal catalysts, extensive application of energy, and the excessive use of hazardous materials. Nanocatalysts play a profound role in sustainable synthesis because of their larger surface area, tiny size, and minimum energy; they are eco-friendly and safe, and they provide higher yields with selectivity in comparison to conventional catalysts. It is increasingly demanding research to design and synthesize novel bioactive compounds that may help to combat cancer since the major causes of death worldwide are due to cancer. Hence, the important uses of nanocatalysts for the one-pot synthesis of biologically potent N,N-heterocycles with anticancer activities have been presented in this review.

N-heterocycles 是有机化学中最主要、最独特的一类化合物。由于其重要的化学、生物医学和工业用途,它们受到了广泛关注。美国食品和药物管理局(FDA)批准了约 75% 含有 N 型杂环的药物,这些药物目前已在市场上销售。N 型杂环化合物是众多天然产物的骨架,也是制造药品、兽药和农用化学品的重要中间体。在 N 基杂环化合物中,具有生物活性的 N,N-杂环化合物在现代药物发现和开发过程中有着广泛的应用。头孢唑喃(抗生素)、奥美拉唑(抗溃疡)、恩维拉定(抗病毒)、利阿罗唑(抗癌)等都是含有 N,N-杂环的重要药物。在可持续条件下合成 N,N-三环化合物是最活跃的领域之一,因为它们具有重要的生理和生物特性以及合成用途。目前的研究要求开发更环保、更便宜、更温和的 N,N-杂环化合物合成方案,以避免使用有毒金属催化剂、大量使用能源和过量使用有害物质,从而拯救大自然。纳米催化剂在可持续合成中发挥着深远的作用,因为它们具有更大的表面积、极小的尺寸和最低的能耗;与传统催化剂相比,它们既环保又安全,还能提供更高的产率和选择性。由于癌症是导致全球死亡的主要原因,因此设计和合成有助于抗癌的新型生物活性化合物的研究要求越来越高。因此,本综述介绍了纳米催化剂在一锅合成具有抗癌活性的生物强效 N,N-杂环方面的重要用途。
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引用次数: 0
Phytochemical Profile and Antioxidant and Protective Activities of Various Types of Extracts from Hyssopus officinalis L. and Grindelia robusta Nutt. Herb Grown in Poland 从 Hyssopus officinalis L. 和 Grindelia robusta Nutt.波兰种植的草本植物
IF 3.4 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-08-28 DOI: 10.2174/0115680266319052240819104310
Monika Michalak, Ewelina Błońska-Sikora, Małgorzata Stryjecka, Martyna Zagórska-Dziok, Marta Klimek-Szczykutowicz, Agnieszka Szopa
Introduction: The available literature indicates that Hyssopus officinalis and Grindelia robusta are raw materials with great potential for use in prevention and therapy. Therefore, the aims of this study were to assess the phytochemical profile and antioxidant and cytoprotective properties of extracts prepared using various solvents, additionally taking into account different methods of drying the plant material. Methods: Hydrodistilled oil was analysed by GC-MS. The chemical composition of the extracts was estimated by spectrophotometry and the HPLC–DAD method. Antioxidant activity was evaluated using DPPH and FRAP and measuring the intracellular level of ROS. Alamar Blue and Neutral Red tests were used to assess the cytotoxicity of the extracts on skin cells - keratinocytes and fibroblasts. Results: The major components of hyssop essential oil were cis- (44.9%) and trans- (18.2%) pinocamphone, while borneol (16.1%), and α-pinene (12.0%) were predominant in grindelia essential oil. Flavonoids were dominant in the extracts (water:ethanol, water:methanol, and water: glycerol) from hot-air dried hyssop herb, while phenolic acids were the predominant compounds in the grindelia herb extracts. The water:ethanol hyssop extract had the highest total content of flavonoids (42.26 mg CE/mL), among which isoquercitrin and rutin were present in the highest quantities (32.61 mg/mL and 21.47 mg/mL, respectively). In the case of grindelia, the highest total phenolic acid content (26.24 mg CAE/mL) was recorded in the water:ethanol extract, and the dominant compounds among them were 1,5-dicaffeoylquinic and chlorogenic acid (10.85 and 6.39 mg/mL, respectively). The water:ethanol extract from both plants also exhibited the highest antioxidant activity in the DPPH and FRAP tests (79.19% and 1.39 mmol/L, respectively, for grindelia and 67.61% and 1.04 mmol/L for hyssop) and was most effective at reducing the level of ROS in cells. In addition, water:ethanol extracts may have a positive impact on the viability of skin cells in vitro. Conclusion: Water:ethanol extracts from H. officinalis and G. robusta herb are promising sources of active compounds and may find application as natural materials with valuable biological properties, which require further in vitro and in vivo testing.
导言:现有文献表明,Hyssopus officinalis 和 Grindelia robusta 是极具预防和治疗潜力的原材料。因此,本研究旨在评估使用不同溶剂制备的提取物的植物化学成分、抗氧化性和细胞保护性,同时考虑到植物材料的不同干燥方法。方法:采用 GC-MS 对水蒸馏油进行分析。通过分光光度法和 HPLC-DAD 法估算提取物的化学成分。使用 DPPH 和 FRAP 评估抗氧化活性,并测量细胞内的 ROS 水平。阿拉玛蓝和中性红测试用于评估提取物对皮肤细胞--角质细胞和成纤维细胞--的细胞毒性。结果百日草精油的主要成分是顺式(44.9%)和反式(18.2%)蒎烷,而研磨精油中主要是龙脑(16.1%)和α-蒎烯(12.0%)。黄酮类化合物在热风干燥的百日草提取物(水:乙醇、水:甲醇和水:甘油)中占主导地位,而酚酸类化合物则是研磨草提取物中的主要化合物。水:乙醇百日草提取物中黄酮类化合物的总含量最高(42.26 毫克 CE/毫升),其中异槲皮素和芦丁的含量最高(分别为 32.61 毫克/毫升和 21.47 毫克/毫升)。磨芋的水乙醇提取物中总酚酸含量最高(26.24 毫克 CAE/毫升),其中最主要的化合物是 1,5-二咖啡酰奎宁酸和绿原酸(分别为 10.85 毫克/毫升和 6.39 毫克/毫升)。在 DPPH 和 FRAP 试验中,这两种植物的水乙醇提取物也表现出最高的抗氧化活性(苦参碱的抗氧化活性分别为 79.19% 和 1.39 毫摩尔/升,百日草的抗氧化活性分别为 67.61% 和 1.04 毫摩尔/升),在降低细胞中的 ROS 水平方面最为有效。此外,水:乙醇提取物可能会对体外皮肤细胞的活力产生积极影响。结论从百日草和罗布麻中提取的水乙醇萃取物是很有前景的活性化合物来源,可作为具有宝贵生物特性的天然材料加以应用,但还需要进一步的体外和体内测试。
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引用次数: 0
Synthetic Strategies of Highly Bioactive Scaffold Bis(indolyl)methane Under Greener Condition- A Comprehensive Review 绿色条件下高生物活性支架双(吲哚基)甲烷的合成策略--综述
IF 3.4 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-08-28 DOI: 10.2174/0115680266319238240821080203
Arijit Kundu, Chhanda Mukhopadhyay
Bis(indolyl)Methanes are a major class of heterocycles with considerable promise for technological and biological applications and being fluorescent active as well. Considering the extensive quantity of work on various synthetic techniques, the objective of this study is to measure the previous and current status of research studies related to different types of Bis(indolyl)methane (BIM) derivatives. Currently, research is focused on developing green synthetic strategies for dependable, sustainable and environmentally friendly synthetic processes. The present literature describes the formation of BIM moieties starting from suitable precursors using conventional reaction procedures, as well as reactions mediated by microwaves, ultrasounds, organocatalysts, transition metal catalysts, metal-free ionic liquid catalysts, and other environmentally friendly reaction protocols. The current review discusses the explosive development of different environmentally friendly synthesis routes for bis(indolyl)methane and its analogues during the past few decades. Moreover, this study includes the biological activities such as antibacterial, anticancer, anti-inflammatory, etc., of BIM derivatives, which have been investigated in recent years.
双(吲哚基)甲烷是一类主要的杂环化合物,在技术和生物应用方面前景广阔,同时还具有荧光活性。考虑到有关各种合成技术的大量工作,本研究的目的是衡量与不同类型的双(吲哚基)甲烷(BIM)衍生物有关的研究的过去和现状。目前,研究的重点是开发绿色合成策略,以实现可靠、可持续和环保的合成工艺。目前的文献介绍了使用传统反应程序从合适的前体开始形成 BIM 分子的情况,以及由微波、超声波、有机催化剂、过渡金属催化剂、无金属离子液体催化剂和其他环境友好型反应方案介导的反应。本综述讨论了过去几十年中双(吲哚基)甲烷及其类似物不同环境友好型合成路线的爆炸性发展。此外,本研究还包括近年来研究的双(吲哚基)甲烷衍生物的生物活性,如抗菌、抗癌、抗炎等。
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引用次数: 0
Harnessing Natural Resources for Advancements in Dengue Virus Treatment 利用自然资源推进登革热病毒治疗
IF 3.4 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-08-28 DOI: 10.2174/0115680266312717240821062535
Nur Aina Najiha Amin Hapis, Nurshamimi Nor Rashid, Yeun-Mun Choo
: Dengue fever, caused by the Dengue virus (DENV) and transmitted by Aedes aegypti mosquitoes, has become endemic in over 100 countries. Despite considerable research, there is a lack of specific drugs for clinical use against dengue. Hence, further exploration to identify anti-- dengue compounds is essential. In recent years, natural products have gained attention for their antiviral properties. Plant-based medicines are particularly appealing due to their safety and low toxicity. This review summarizes natural compounds with potential antiviral activity against DENV, highlighting their mechanisms of action. Various compounds, from traditional herbal remedies to novel plant isolates, show promise against dengue, targeting crucial viral proteins like the envelope protein, proteases, and RNA polymerase. Exploring natural sources of antiviral agents against dengue is crucial. These compounds offer hope for effective treatments and mitigating dengue's global impact.
:登革热由登革病毒(DENV)引起,由埃及伊蚊传播,已在 100 多个国家流行。尽管开展了大量研究,但临床上仍缺乏针对登革热的特效药物。因此,进一步探索抗登革热化合物至关重要。近年来,天然产品因其抗病毒特性而备受关注。以植物为基础的药物因其安全性和低毒性而特别具有吸引力。本综述总结了对 DENV 具有潜在抗病毒活性的天然化合物,并强调了它们的作用机制。从传统草药到新型植物分离物,各种化合物针对包膜蛋白、蛋白酶和 RNA 聚合酶等关键病毒蛋白,显示出了抗登革热的前景。探索登革热抗病毒药物的天然来源至关重要。这些化合物为有效治疗和减轻登革热的全球影响带来了希望。
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引用次数: 0
Catalase: A Potential Pharmacologic Target for Hydrogen Peroxide in the Treatment of COVID-19 过氧化氢酶:过氧化氢治疗 COVID-19 的潜在药理靶点
IF 3.4 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-08-28 DOI: 10.2174/0115680266322046240819053909
Aleksandr Urakov, Natalya Urakova, Aleksey Reshetnikov, Aleksey Shklyaev, Vladimir Nikolenko, Anatoly Osipov, Natalya Klyachko, Yulia Sorokina, Nikita Muhutdinov, Sergey Okovityi, Petr Shabanov
: This manuscript is a meta-analysis performed according to PRISMA guidelines. It shows that acute respiratory distress syndrome in COVID-19 complicated by airway obstruction with sputum and mucus, as well as cases of asphyxia with blood, serous fluid, pus, or meconium, can sometimes cause hypoxemia because the medical standard does not include intrapulmonary solutions that release oxygen. One promising avenue for finding and developing the necessary drugs may be the physical-chemical repurposing of hydrogen peroxide solution from antiseptics into inhaled and intrapulmonary mucolytics, pyolytics, and oxygen-releasing antihypoxants by replacing the acidic properties of hydrogen peroxide with alkaline properties. The fact is that an alkaline hydrogen peroxide solution liquefies said biological masses through alkaline saponification of lipid and protein-lipid complexes and simultaneously “blasts” the masses through catalase cleavage of hydrogen peroxide into water and oxygen gas, since these masses are rich in catalase. The results of the first experiments show that inhalation and intrapulmonary injections of alkaline hydrogen peroxide solutions can significantly optimize the treatment of suffocation and hypoxemia. Value of the data: 1. Why are these data useful? These data provide a new perspective way for intrapulmonary drugs and new technologies for the emergency increase of blood oxygenation through the lungs in asphyxia with thick sputum, mucus, pus, meconium and blood. 2. Who can benefit from these data? New drug developers, drug manufacturers, medical professionals providing emergency medical care, as well as pulmonologists, physiatrists, obstetricians and gynecologists can benefit from the data presented in this article. 3. How can these data be used/reused for further insights or development of experiments? These data can be used to develop new drugs and new technologies for the treatment of suffocation and hypoxia in the final stage of COVID-19, severe asthma attacks, purulent obstructive bronchitis, blood asphyxia in cancer and wounded lung in intensive care and anesthesiology departments. In addition, these data can be used to modernize expectorant, mucolytic, pyolytic, hemolytic and meconiolytic and expand the arsenal of intrapulmonary drugs.
:本稿件是根据 PRISMA 指南进行的荟萃分析。它表明,COVID-19 中因痰液和粘液导致气道阻塞而并发的急性呼吸窘迫综合征,以及因血液、浆液、脓液或胎粪导致的窒息病例,有时会引起低氧血症,因为医疗标准不包括释放氧气的肺内溶液。寻找和开发必要药物的一个很有希望的途径可能是将过氧化氢溶液从防腐剂转变为吸入和肺内粘液溶解剂、溶脓剂和释放氧气的抗低氧血症剂,用碱性取代过氧化氢的酸性。事实上,碱性过氧化氢溶液通过碱性皂化脂质和蛋白质-脂质复合物,使上述生物质液化,同时通过过氧化氢的过氧化氢酶裂解为水和氧气,使生物质 "爆炸",因为这些生物质富含过氧化氢酶。首次实验结果表明,吸入和肺内注射碱性过氧化氢溶液可显著优化窒息和低氧血症的治疗。数据的价值:1.为什么这些数据有用?这些数据为肺内药物和新技术提供了新的视角方式,可在痰液、粘液、脓液、胎粪和血液粘稠的窒息情况下,通过肺部紧急增加血液含氧量。2.谁能从这些数据中获益?新药研发人员、药品生产商、提供紧急医疗护理的专业医务人员以及肺科医生、物理治疗师、产科医生和妇科医生均可从本文提供的数据中获益。3.如何使用/重复使用这些数据来进一步深入了解或开发实验?这些数据可用于开发新药物和新技术,以治疗 COVID-19 最后阶段的窒息和缺氧、严重哮喘发作、化脓性阻塞性支气管炎、癌症中的血液窒息以及重症监护和麻醉科的伤肺。此外,这些数据还可用于使祛痰剂、粘液溶解剂、溶脓剂、溶血剂和溶菌剂现代化,并扩大肺内药物库。
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引用次数: 0
Therapeutic Potential of Quercetin in Diabetic Neuropathy and Retinopathy: Exploring Molecular Mechanisms 槲皮素在糖尿病神经病变和视网膜病变中的治疗潜力:探索分子机制
IF 3.4 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-08-28 DOI: 10.2174/0115680266330678240821060623
Lunasmrita Saikia, Sm Abdul Aziz Barbhuiya, Kalyani Saikia, Pratap Kalita, Partha Pratim Dutta
Diabetes mellitus poses a significant health challenge globally, often leading to debilitating complications, such as neuropathy and retinopathy. Quercetin, a flavonoid prevalent in fruits and vegetables, has demonstrated potential therapeutic effects in these conditions due to its antioxidant, anti-inflammatory, and neuroprotective properties. This review summarizes and provides a comprehensive understanding of the molecular mechanisms underlying the efficacy of quercetin in ameliorating diabetic neuropathy and retinopathy. A thorough search was carried out across scientific databases, such as SciFinder, PubMed, and Google Scholar, to gather pertinent literature regarding the effect of quercetin on diabetic neuropathy and retinopathy till February 2024. Preclinical studies indicate that quercetin mitigates neuropathic pain, sensory deficits, and nerve damage associated with diabetic neuropathy by improving neuronal function, reducing DNA damage, regulating pro-inflammatory cytokines, enhancing antioxidant enzyme levels and endothelial function, as well as restoring nerve injuries. In diabetic retinopathy, quercetin shows the potential to preserve retinal structure and function, inhibiting neovascularization, preventing retinal cell death, reducing pro-inflammatory cytokines, and increasing neurotrophic factor levels. Moreover, through modulating key signaling pathways, such as AMP-activated Protein Kinase (AMPK) activation, Glucose Transporter 4 (GLUT 4) upregulation, and insulin secretion regulation, quercetin demonstrates efficacy in reducing oxidative stress and inflammation, thereby protecting nerve and retinal tissues. Despite promising preclinical findings, challenges, such as limited bioavailability, necessitate further research to optimize quercetin’s clinical application in order to establish its optimal dosage, formulation, and long-term efficacy in clinical settings.
糖尿病是全球面临的一项重大健康挑战,通常会导致神经病变和视网膜病变等使人衰弱的并发症。槲皮素是一种普遍存在于水果和蔬菜中的类黄酮,由于其抗氧化、抗炎和保护神经的特性,它对这些病症具有潜在的治疗作用。本综述总结并全面阐述了槲皮素在改善糖尿病神经病变和视网膜病变方面功效的分子机制。我们在SciFinder、PubMed和Google Scholar等科学数据库中进行了全面搜索,收集了截至2024年2月有关槲皮素对糖尿病神经病变和视网膜病变影响的相关文献。临床前研究表明,槲皮素可通过改善神经元功能、减少 DNA 损伤、调节促炎细胞因子、提高抗氧化酶水平和内皮功能以及恢复神经损伤,减轻与糖尿病神经病变相关的神经性疼痛、感觉障碍和神经损伤。在糖尿病视网膜病变中,槲皮素显示出保护视网膜结构和功能的潜力,它能抑制新生血管,防止视网膜细胞死亡,减少促炎细胞因子,提高神经营养因子水平。此外,通过调节关键信号通路,如激活 AMP 激活蛋白激酶 (AMPK)、上调葡萄糖转运体 4 (GLUT 4) 和调节胰岛素分泌,槲皮素可有效降低氧化应激和炎症反应,从而保护神经和视网膜组织。尽管临床前研究结果令人鼓舞,但由于生物利用度有限等挑战,有必要开展进一步研究,以优化槲皮素的临床应用,从而确定其在临床环境中的最佳剂量、配方和长期疗效。
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引用次数: 0
Pro-Inflammatory Signaling Cascade Markers, Oxidative Stress-Inflammatory Signaling Axis, and Chronic Total Occlusion of Tibial Artery in Elderly Patients Suffering from Occlusion of Coronary Arteries 冠状动脉闭塞老年患者的促炎症信号级联标记、氧化应激-炎症信号轴与胫动脉慢性全闭塞
IF 3.4 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-08-28 DOI: 10.2174/0115680266306301240821073416
Xia Li, Yongjuan Zhao, Hualan Zhou, Youdong Hu, Ying Chen, Dianxuan Guo
Introduction: Oxidative response is a risk factor in the progression of arterial atherosclerosis. Objective: This research study aimed to examine the effects of oxidative response on atherosclerotic susceptibility as well as the development of arteriosclerosis occlusions of the tibial artery through pro-inflammatory mediator genes in elderly patients with occlusion of coronary arteries. Methods: We determined that oxidative stress biomarkers (Malondialdehyde-modified Low-density Lipoprotein (MDA-LDL), Oxidized Low-density Lipoprotein (Ox-LDL) as well as Heme Oxygenase- 1 (HO-1)] and the expressions of pro-inflammatory mediator genes [Toll-like Receptor 4 (TLR4), Nuclear Factor kappa-B (NF-κB), Myeloid Differentiating factor 88 (MyD88) and Growth Arrest-specific gene 6 (GAS6)] have an impact on the severity of arteriosclerosis occlusions of tibial artery in elderly patients suffering from occlusion of coronary arteries. Results: Levels of MDA-LDL, Ox-LDL, HO-1, TLR4, NF-κB, MyD88, and GAS6 were increased in the occlusion of tibial arteries + two-vessel coronary occlusion group compared to the CON group and occlusion of tibial arteries + one-vessel coronary occlusion group, respectively (p < 0.001); they were also elevated in occlusion of tibial arteries + multiple-vessel coronary occlusion group compared to occlusion of tibial arteries + one-vessel coronary occlusion group and occlusion of tibial arteries + two-vessel coronary occlusion group, respectively (P < 0.001). This has indicated the key roles of oxidative stress and pro-inflammatory mediator genes in arteriosclerosis occlusions of tibial artery in elderly patients with occlusion of coronary arteries. Conclusion: Oxidative response may promote the expressions of inflammatory genes and enhance susceptibility to arteriosclerosis occlusions of the tibial artery in elderly patients with chronic total coronary occlusions.
导言氧化反应是动脉粥样硬化恶化的一个危险因素。研究目的本研究旨在探讨氧化反应对动脉粥样硬化易感性的影响,以及通过促炎介质基因对老年冠状动脉闭塞患者胫骨动脉硬化闭塞症的发展产生的影响。方法核因子卡巴-B(NF-κB)、髓样分化因子 88(MyD88)和生长停滞特异基因 6(GAS6)]的表达对老年冠状动脉闭塞患者胫动脉动脉硬化闭塞症的严重程度有影响。研究结果MDA-LDL、Ox-LDL、HO-1、TLR4、NF-κB、MyD88和GAS6的水平在胫动脉闭塞+双血管冠状动脉闭塞组分别高于CON组和胫动脉闭塞+单血管冠状动脉闭塞组(P < 0.001);与胫动脉闭塞+一脉冠状动脉闭塞组和胫动脉闭塞+二脉冠状动脉闭塞组相比,胫动脉闭塞+多脉冠状动脉闭塞组也分别升高(P < 0.)这表明氧化应激和促炎介质基因在老年冠状动脉闭塞患者胫动脉硬化闭塞中起着关键作用。结论氧化反应可能会促进炎症基因的表达,并增加慢性冠状动脉全闭塞老年患者胫动脉硬化闭塞的易感性。
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引用次数: 0
Tackling Neuroinflammation in Cognitive Disorders with Single-Targeted and Multi-Targeted Histamine H3 Receptor Modulators. 利用单靶点和多靶点组胺 H3 受体调节剂解决认知障碍中的神经炎症问题
IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-08-23 DOI: 10.2174/0115680266322294240816051818
Flávia Barrio Lopes, João Paulo S Fernandes, Elisa Uliassi

Neuroinflammation is a process involved in a variety of central nervous system (CNS) diseases and is being increasingly recognized as a key mediator of cognitive impairments. Neuroinflammatory responses including glial activation, increased production of proinflammatory cytokines, and aberrant neuronal signaling, contribute to cognitive dysfunctions. Histamine is a key peripheral inflammatory mediator, but plays an important role in neuroinflammatory processes as well. The unique localization of histamine H3 receptor (H3R) in the CNS along with the modulation of the release of other neurotransmitters via its action on heteroreceptors on non-histaminergic neurons have led to the development of several H3R ligands for various brain diseases. H3R antagonists/ inverse agonists have revealed potential to treat diverse neuroinflammatory CNS disorders, including neurodegenerative diseases, attention-deficit hyperactivity syndrome and schizophrenia. In this mini review, we provide a brief overview on the crucial involvement of the histaminergic transmission in the neuroinflammatory processes underlying these cognitive disorders, with a special focus on H3R involvement. The anti-neuroinflammatory potential of single-targeted and multi-targeted H3R antagonists/inverse agonists for the treatment of these conditions is discussed here.

神经炎症是一种涉及多种中枢神经系统(CNS)疾病的过程,而且越来越被认为是认知障碍的一个关键介质。神经炎症反应包括神经胶质细胞活化、促炎细胞因子分泌增加和神经元信号传导异常,这些都会导致认知功能障碍。组胺是一种关键的外周炎症介质,但在神经炎症过程中也发挥着重要作用。组胺 H3 受体(H3R)在中枢神经系统中的独特定位,以及它通过作用于非组胺能神经元上的异受体对其他神经递质释放的调节作用,促使人们开发出多种 H3R 配体来治疗各种脑部疾病。H3R拮抗剂/反向激动剂已显示出治疗各种神经炎症性中枢神经系统疾病的潜力,包括神经退行性疾病、注意力缺陷多动综合征和精神分裂症。在这篇微型综述中,我们将简要概述组胺能传导在这些认知障碍的神经炎症过程中的重要参与,并特别关注 H3R 的参与。本文讨论了单靶点和多靶点 H3R 拮抗剂/反激动剂治疗这些疾病的抗神经炎症潜力。
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引用次数: 0
Ligand-Based Approach for Multi-Target Drug Discovery: PTML Modeling of Triple-Target Inhibitors. 基于配体的多靶点药物发现方法:三靶点抑制剂的 PTML 模型。
IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-08-21 DOI: 10.2174/0115680266325897240815112505
Valeria V Kleandrova, M Natália D S Cordeiro, Alejandro Speck-Planche

Background: Cancers are complex multi-genetic diseases that should be tackled in multi-target drug discovery scenarios. Computational methods are of great importance to accelerate the discovery of multi-target anticancer agents. Here, we employed a ligand-based approach by combining a perturbation-theory machine learning model derived from an ensemble of multilayer perceptron networks (PTML-EL-MLP) with the Fragment-Based Topological Design (FBTD) approach to rationally design and predict triple-target inhibitors against the cancerrelated proteins named Tropomyosin Receptor Kinase A (TRKA), poly[ADP-ribose] polymerase 1 (PARP-1), and Insulin-like Growth Factor 1 Receptor (IGF1R).

Methods: We extracted the chemical and biological data from ChEMBL. We applied the Box- Jenkins approach to generate multi-label topological indices and subsequently created the PTML-EL-MLP model.

Results: Our PTML-EL-MLP model exhibited an accuracy of around 80%. The application FBTD permitted the physicochemical and structural interpretation of the PTML-EL-MLP model, thus enabling a) the chemistry-driven analysis of different molecular fragments with a positive influence on the multi-target activity and b) the use of those favorable fragments as building blocks to virtually design four new drug-like molecules. The designed molecules were predicted as triple-target inhibitors against the aforementioned cancer-related proteins.

Conclusion: Our study envisages the capabilities of combining PTML modeling with FBTD for the generation of new chemical diversity for multi-target drug discovery in oncology research and beyond.

背景:癌症是一种复杂的多基因疾病,应在多靶点药物发现方案中加以解决。计算方法对于加速多靶点抗癌药物的发现非常重要。在这里,我们采用了一种基于配体的方法,将从多层感知器网络集合(PTML-EL-MLP)中衍生出的扰动理论机器学习模型与基于片段的拓扑设计(FBTD)方法相结合,合理地设计和预测了针对肿瘤相关蛋白--肌球蛋白受体激酶A(TRKA)、聚[ADP-核糖]聚合酶1(PARP-1)和胰岛素样生长因子1受体(IGF1R)--的三靶点抑制剂:我们从 ChEMBL 中提取了化学和生物学数据。方法:我们从 ChEMBL 中提取了化学和生物数据,并采用 Box- Jenkins 方法生成了多标签拓扑指数,随后创建了 PTML-EL-MLP 模型:结果:我们的 PTML-EL-MLP 模型显示出约 80% 的准确率。应用 FBTD 可以对 PTML-EL-MLP 模型进行物理化学和结构解释,从而能够:(a)从化学角度分析对多靶点活性有积极影响的不同分子片段;(b)利用这些有利片段作为构建模块,虚拟设计出四种新的类药物分子。所设计的分子被预测为针对上述癌症相关蛋白的三靶点抑制剂:我们的研究设想了将 PTML 建模与 FBTD 结合起来,为肿瘤学研究及其他领域的多靶点药物发现创造新的化学多样性的能力。
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引用次数: 0
Literature-based Survey of Medicinal Plants Since 1900: A Case Study to Treat Cancer in the Sultanate of Oman. 对 1900 年以来药用植物的文献调查:阿曼苏丹国癌症治疗案例研究》。
IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Pub Date : 2024-08-21 DOI: 10.2174/0115680266318053240819100111
Asif Khan, Ajmal Khan, Waheed Murad, Sobia Ahsan Halim, Hammad Ahmad Jan, Mohammed Al-Broumi, Ahmed Al-Harrasi

Ethnopharmacological relevance: Due to the high prevalence of cancer, researchers for the past decades have made considerable efforts for its management and treatment. Medicinal plants have always been exploited to discover novel anticancer agents. Oman's huge biodiversity has created a rich source of traditional medicine.

Objective: The current survey has aimed to document the traditionally used medicinal plants of Oman and their therapeutic role in the treatment of cancer.

Material method: This study comprises of literature-based survey through different databases, including Google, Scopus, Google Scholar, Web of Science, Science Direct, Springer Link, BioMed Central and PubMed.

Results: The current review revealed a total of 57 plant species that belong to 35 families that are used in the treatment of cancer in Oman. Most documented plants belong to Solanaceae (6 sp.), Apocyanaceae (5 sp.) and Lamiaceae (4 sp.). The literature reveals that the residents of the area mostly use leaves (38.5%) and prepare their recipes in the form of decoction (40.3%). Moreover, herbs are the most dominant life form (43.85%). Among all forms of cancer in Oman, breast (47%), wound (26), and lung cancer (0.5%) were found dominantly. A literature study confirmed that the medicinal plants used for cancer in Oman are rich in phytochemicals such as quercetin, allicin, coumarin, alliin, kaempferol, solamargine, rutin, lupeol, ursolic acid and luteolin that have shown significant biological activities including anti-cancer potential. It reflects the efficacy of these plants to be used as a medicine in clinical trials. Among all, Boswellia sacra Flueck. is of key importance due to the presence Boswellic acid being used for the treatment of different types of cancer.

Conclusion: The residents of Oman have great knowledge about the traditional use of medicinal plants for the treatment of various diseases like cancer. The therapeutic potential and physiological efficacy of Omani medicinal plants should be further explored at a molecular level via in vivo and in vitro experiments.

民族药理学意义:由于癌症的高发病率,过去几十年来,研究人员为癌症的管理和治疗做出了巨大努力。人们一直在利用药用植物来发现新型抗癌剂。阿曼巨大的生物多样性为传统医药提供了丰富的资源:本次调查旨在记录阿曼的传统药用植物及其在治疗癌症方面的作用:本研究通过不同的数据库(包括 Google、Scopus、Google Scholar、Web of Science、Science Direct、Springer Link、BioMed Central 和 PubMed)进行文献调查:目前的研究显示,阿曼共有 35 个科的 57 种植物被用于治疗癌症。大多数记录在案的植物属于茄科(6 种)、花青素科(5 种)和苎麻科(4 种)。文献显示,该地区的居民大多使用叶子(38.5%),并以煎煮(40.3%)的形式制作食谱。此外,草药是最主要的生命形式(43.85%)。在阿曼的各种癌症中,主要是乳腺癌(47%)、伤口癌(26%)和肺癌(0.5%)。一项文献研究证实,阿曼用于治疗癌症的药用植物含有丰富的植物化学物质,如槲皮素、大蒜素、香豆素、大蒜素、山柰酚、索拉马金碱、芦丁、羽扇豆醇、熊果酸和木犀草素,这些物质具有显著的生物活性,包括抗癌潜力。这反映了这些植物在临床试验中作为药物使用的功效。其中,Boswellia sacra Flueck.由于含有乳香酸而被用于治疗不同类型的癌症,因此具有重要意义:阿曼居民对传统上使用药用植物治疗癌症等各种疾病非常了解。阿曼药用植物的治疗潜力和生理功效应通过体内和体外实验在分子水平上进一步探索。
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引用次数: 0
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Current topics in medicinal chemistry
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