Natural inhibitors

天然抑制剂
  • 背景:糖尿病(DM)是全球近5亿人口中普遍存在的严重健康问题。它是最具威胁性的代谢性疾病之一。2型DM是由于胰岛素抵抗引起的,占糖尿病病例的90%。如果没有得到治疗,它可能导致重大的可怕的并发症,并可能导致死亡,最终威胁到人类。
    结论:目前有各种口服降血糖药物,通过采用不同的途径作用于不同的靶标。然而,α-葡萄糖苷酶抑制剂被证明是治疗T2DM的一种新的有效策略。这些抑制剂通过竞争性和可逆地抑制肠道α-葡萄糖苷酶来缓解餐后血糖,从而延缓碳水化合物的消化,降低葡萄糖的吸收速度。大量的α-葡萄糖苷酶抑制剂已经从合成途径以及从天然来源,包括植物,真菌,和细菌。
    结论:本文包含2016年至2021年发现的天然和合成α-葡萄糖苷酶,可用于发现新型α-葡萄糖苷酶抑制剂。本文综述了α-葡萄糖苷酶抑制剂的发现和开发进展。这可以为使用这些信息开发临床可行药物的药物化学家提供概述。
    BACKGROUND: Diabetes mellitus (DM) is a critical health issue prevailing in nearly half a billion people worldwide. It is one of the most threatening metabolic diseases. Type 2 DM is caused due to insulin resistance and accounts for 90% of diabetes cases. If it remains untreated, it can lead to major frightening complications and can cause death, which ultimately threatens humankind.
    CONCLUSIONS: Various oral hypoglycaemic drugs are available today, acting on different targets by adopting different pathways. However, the α-glucosidase inhibitors proved to be a novel and effective strategy to manage T2DM. These inhibitors alleviate postprandial glycemia by aiming to inhibit intestinal α-glucosidase competitively and reversibly, thus delaying carbohydrate digestion and turning down the rate of glucose absorption. Plenty of α-glucosidase inhibitors have been discovered from synthetic routes as well as from natural sources, including plants, fungi, and bacteria.
    CONCLUSIONS: This article comprises the natural and synthetic α-glucosidase discovered from 2016 to 2021 and can be utilized to discover novel α-glucosidase inhibitors. This review is an endeavor to highlight the progress in the discovery and development of α-glucosidase inhibitors, which could provide an overview to the medicinal chemists for the development of clinically viable drugs using this information.
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  • 文章类型: Journal Article
    背景:传统治疗师在世界范围内使用药用植物来治疗蛇咬伤;然而,大多没有科学验证。已经有许多关于天然产物对抗蛇毒的治疗潜力的研究。
    目的:这篇综述强调了来自植物的生物活性化合物和肽的蛇毒抑制活性,这些化合物和肽已发现用于治疗蛇咬伤毒液的传统用途。我们系统地回顾了从1994年到现在的天然蛇毒抑制剂表征的不同阶段的情况,并批判性地分析了研究的空白(如果有的话),以及从长凳到床边的进一步翻译范围。
    方法:从公共数据库(Scopus,MEDLINE)从1994年到2020年。使用的搜索词是对蛇咬伤的天然抑制剂,\'\'天然产品作为治疗蛇咬伤,\'\'天然产品作为对抗蛇毒的解毒剂,\'\'蛇毒毒素天然抑制剂,\'\'蛇毒草药抑制剂\'。然而,本综述的范围不包括没有任何湿实验室验证的计算(计算机模拟)预测和粗植物提取物的蛇毒抑制活性。此外,我们还预测了已鉴定的蛇毒抑制剂的ADMET特性,以突出其对未来临床研究有价值的药代动力学.
    结果:植物来源的天然抑制剂作为抗蛇毒血清疗法的辅助治疗蛇咬伤的治疗应用已获得了显着的势头。对源自传统药用植物的天然化合物的药理学重新评估表明,可以在不同程度上抑制蛇毒的主要毒性酶,以遏制毒蛇咬伤的致命和/或有害作用。然而,这些分子尚未商业化用于治疗蛇咬伤的临床应用。植物来源的天然产物作为蛇毒解毒剂的适销性存在许多障碍,必须探索将这些化合物从候选药物转化为临床应用的策略。
    结论:为了尽量减少蛇毒的不利影响,必须制定策略,以使这些植物衍生的小分子抑制剂从工作台到床边的平稳过渡。在本文中,我们提出了一个包容性的审查,并批判性地分析了天然产品对蛇毒的治疗潜力,并提出了使用天然产品作为蛇咬伤解毒剂的路线图。
    BACKGROUND: Traditional healers have used medicinal plants to treat snakebite envenomation worldwide; however, mostly without scientific validation. There have been many studies on the therapeutic potential of the natural products against snake envenomation.
    OBJECTIVE: This review has highlighted snake venom inhibitory activity of bioactive compounds and peptides from plants that have found a traditional use in treating snakebite envenomation. We have systematically reviewed the scenario of different phases of natural snake venom inhibitors characterization covering a period from 1994 until the present and critically analysed the lacuna of the studies if any, and further scope for their translation from bench to bedside.
    METHODS: The medicinal plant-derived compounds used against snakebite therapy were reviewed from the available literature in public databases (Scopus, MEDLINE) from 1994 till 2020. The search words used were \'natural inhibitors against snakebite,\' \'natural products as therapeutics against snakebite,\' \'natural products as antidote against snake envenomation,\' \' snake venom toxin natural inhibitors,\' \'snake venom herbal inhibitors\'. However, the scope of this review does not include computational (in silico) predictions without any wet laboratory validation and snake venom inhibitory activity of the crude plant extracts. In addition, we have also predicted the ADMET properties of the identified snake venom inhibitors to highlight their valuable pharmacokinetics for future clinical studies.
    RESULTS: The therapeutic application of plant-derived natural inhibitors to treat snakebite envenomation as an auxiliary to antivenom therapy has been gaining significant momentum. Pharmacological reassessment of the natural compounds derived from traditional medicinal plants has demonstrated inhibition of the principal toxic enzymes of snake venoms at various extents to curb the lethal and/or deleterious effects of venomous snakebite. Nevertheless, such molecules are yet to be commercialized for clinical application in the treatment of snakebite. There are many obstacles in the marketability of the plant-derived natural products as snake envenomation antidote and strategies must be explored for the translation of these compounds from drug candidates to their clinical application.
    CONCLUSIONS: In order to minimize the adverse implications of snake envenomation, strategies must be developed for the smooth transition of these plant-derived small molecule inhibitors from bench to bedside. In this article we have presented an inclusive review and have critically analysed natural products for their therapeutic potential against snake envenomation, and have proposed a road map for use of natural products as antidote against snakebite.
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  • 文章类型: Journal Article
    涉及蛋白质中还原糖的羰基和氨基的非酶反应产生晚期糖基化终产物(AGEs)。体内AGE积累是肥胖等代谢和病理生理机制进展的关键因素,糖尿病,冠状动脉疾病,神经系统疾病,慢性肾功能衰竭.身体自身的防御机制,合成抑制剂,和天然抑制剂都可以帮助防止蛋白质的糖基化。合成抑制剂具有通过多种途径抑制蛋白质糖基化的潜力。他们可以通过篡改向蛋白质中添加糖来避免Amadori产品开发。除此之外,自由基清除和阻止交联形成可能是其抗糖基化特性背后的另一种机制。与合成物质相比,已发现天然植物产品相对无毒,便宜,并以可摄取的形式使用。这篇综述简要介绍了美拉德反应;形成,与AGEs相关的表征和病理,针对糖基化的潜在治疗方法,天然和合成的糖基化抑制剂及其可能的作用机制。科学界可以从关于重要分子的综合知识中受益,这将进一步指导新药物化合物的设计和开发。
    Non-enzymatic reaction involving carbonyl of reducing sugars and amino groups in proteins produces advanced glycation end products (AGEs). AGE accumulation in vivo is a crucial factor in the progression of metabolic and pathophysiological mechanisms like obesity, diabetes, coronary artery disease, neurological disorders, and chronic renal failure. The body\'s own defense mechanism, synthetic inhibitors, and natural inhibitors can all help to prevent the glycation of proteins. Synthetic inhibitors have the potential to suppress the glycation of proteins through a variety of pathways. They could avoid Amadori product development by tampering with the addition of sugars to the proteins. Besides which, the free radical scavenging and blocking crosslink formation could be another mechanism behind their anti-glycation properties. In comparison with synthetic substances, naturally occurring plant products have been found to be comparatively non-toxic, cheap, and usable in an ingestible form. This review gives a brief introduction of the Maillard reaction; formation, characterization and pathology related to AGEs, potential therapeutic approaches against glycation, natural and synthetic inhibitors of glycation and their probable mechanism of action. The scientific community could get benefit from the combined knowledge about important molecules, which will further guide to the design and development of new pharmaceutical compounds.
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  • 文章类型: Journal Article
    冠状病毒已经在全球范围内受到持续关注,因为它们已经对全球公共卫生造成了严重威胁。这组病毒的命名是由于它们在其蛋白质外壳上表现出特征性的冠状尖峰。SARS-CoV-2是2019年出现的一种冠状病毒,在人类下呼吸道引起严重感染,通常在免疫功能低下的个体中致命。目前还没有批准直接治疗SARS-CoV-2感染的药物,目前可用的治疗方案依赖于缓解症状。自然界中存在的药用植物作为活性成分的丰富来源,可用于开发具有抗病毒特性的药典和非药典/合成药物。从某些植物中获得的化合物已被用于直接和选择性地抑制不同的冠状病毒,包括SARS-CoV,MERS-CoV,和SARS-CoV-2.本综述讨论了针对高致病性人类冠状病毒的潜在天然抑制剂,系统阐述了这些天然化合物在冠状病毒生命周期的不同阶段发挥作用的可能机制。此外,通过对这方面现有文献的全面探索,讨论了这些化合物在研究和开发有效和安全的抗病毒药物中的重要性。我们专注于几种天然化合物的作用机理及其作用目标。此外,阐明了这些活性成分在人类健康中的免疫调节作用。最后,有人认为,使用传统药用植物是一种新颖可行的针对人类冠状病毒的补救策略。
    Coronaviruses have been receiving continuous attention worldwide as they have caused a serious threat to global public health. This group of viruses is named so as they exhibit characteristic crown-like spikes on their protein coat. SARS-CoV-2, a type of coronavirus that emerged in 2019, causes severe infection in the lower respiratory tract of humans and is often fatal in immunocompromised individuals. No medications have been approved so far for the direct treatment of SARS-CoV-2 infection, and the currently available treatment options rely on relieving the symptoms. The medicinal plants occurring in nature serve as a rich source of active ingredients that could be utilized for developing pharmacopeial and non-pharmacopeial/synthetic drugs with antiviral properties. Compounds obtained from certain plants have been used for directly and selectively inhibiting different coronaviruses, including SARS-CoV, MERS-CoV, and SARS-CoV-2. The present review discusses the potential natural inhibitors against the highly pathogenic human coronaviruses, with a systematic elaboration on the possible mechanisms of action of these natural compounds while acting in the different stages of the life cycle of coronaviruses. Moreover, through a comprehensive exploration of the existing literature in this regard, the importance of such compounds in the research and development of effective and safe antiviral agents is discussed. We focused on the mechanism of action of several natural compounds along with their target of action. In addition, the immunomodulatory effects of these active components in the context of human health are elucidated. Finally, it is suggested that the use of traditional medicinal plants is a novel and feasible remedial strategy against human coronaviruses.
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  • 文章类型: Journal Article
    简介:蛋白酪氨酸磷酸酶1B(PTP1B)抑制已被推荐为增强各种细胞中胰岛素敏感性的关键策略,这一事实得到了人类基因数据的支持。PTP1B抑制剂可改善胰岛素受体的敏感性,并具有治愈胰岛素抵抗相关疾病的能力。在后来的几年里,靶向PTP1B抑制剂被认为是治疗T2DM的有吸引力的靶点,因此PTP1B抑制剂文库被认为是有效的抗糖尿病药物.涵盖的领域:本审查概述了2015年1月至2018年12月已发布的专利。该综述描述了有效的PTP1B抑制剂作为治疗2型糖尿病的药物的有效性。专家意见:PTP1B药物发现已经取得了巨大的进展,描述了天然产物的进展,合成杂环支架或杂环杂化化合物。正在遵循各种方案来增强PTP1B抑制剂的药理作用。此外,这些新的进展表明,有可能获得具有所需效力和选择性的小分子PTP1B抑制剂。此外,通过使用药物化学和结构生物学的综合策略,未来的研究有望导致有效和选择性的PTP1B抑制剂以及更安全和更有效的口服药物。
    Introduction: Protein tyrosine phosphatase 1B (PTP1B) inhibition has been recommended as a crucial strategy to enhance insulin sensitivity in various cells and this fact is supported by human genetic data. PTP1B inhibitors improve the sensitivity of the insulin receptor and have the ability to cure insulin resistance-related diseases. In the latter years, targeting PTP1B inhibitors is being considered an attractive target to treat T2DM and therefore libraries of PTP1B inhibitors are being suggested as potent antidiabetic drugs. Areas covered: This review provides an overview of published patents from January 2015 to December 2018. The review describes the effectiveness of potent PTP1B inhibitors as pharmaceutical agents to treat type 2 diabetes. Expert opinion: Enormous developments have been made in PTP1B drug discovery which describes progress in natural products, synthetic heterocyclic scaffolds or heterocyclic hybrid compounds. Various protocols are being followed to boost the pharmacological effects of PTP1B inhibitors. Moreover these new advancements suggest that it is possible to get small-molecule PTP1B inhibitors with the required potency and selectivity. Furthermore, future endevours via an integrated strategy of using medicinal chemistry and structural biology will hopefully result in potent and selective PTP1B inhibitors as well as safer and more effective orally available drugs.
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