Structure activity relationship

构效关系
  • 文章类型: Journal Article
    黄嘌呤氧化酶(XO)抑制剂,合成和半合成,在过去的几十年里得到了广泛的发展。XO水平的升高不仅是痛风的主要原因,也是与高尿酸血症相关的各种疾病的原因。比如心血管疾病,慢性肾脏疾病,糖尿病,阿尔茨海默病和慢性伤口。市售XO抑制剂(别嘌呤醇,非布索坦,和topiroxostat)用于治疗高尿酸血症,但它们与致命的副作用有关,这给医疗保健系统带来了严重的问题,提高对新的需求,更有效,更安全的化合物。这篇综述总结了XO的最新发现,并描述了他们的设计,合成,在开发具有ADME谱的抗高尿酸血症药物中的生物学意义,构效关系(SAR)和分子对接研究。该结果可能有助于药物化学家开发更有效的XO抑制剂。
    Xanthine oxidase (XO) inhibitors, both synthetic and semisynthetic, have been developed extensively over the past few decades. The increased level of XO is not only the major cause of gout but is also responsible for various conditions associated with hyperuricemia, such as cardiovascular disorders, chronic kidney disorders, diabetes, Alzheimer\'s disease and chronic wounds. Marketed available XO inhibitors (allopurinol, febuxostat, and topiroxostat) are used to treat hyperuricemia but they are associated with fatal side effects, which pose serious problems for the healthcare system, rising the need for new, more potent, safer compounds. This review summarizes recent findings on XO and describes their design, synthesis, biological significance in the development of anti-hyperuricemic drugs with ADME profile, structure activity relationship (SAR) and molecular docking studies. The results might help medicinal chemists to develop more efficacious XO inhibitors.
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  • 文章类型: Journal Article
    亚洲国家长期以来一直将食用菌用作食品和药品。多糖是真菌细胞壁的主要结构单元之一。真菌多糖已在医药和工业部门作为具有广泛的各种生物活性和应用的产品,如抗肿瘤,抗氧化剂,抗癌,免疫调节,和抗病毒活性,等。这篇综述的目的是深入了解蘑菇多糖的各种生物活性及其作为人类健康药物的潜力。提取,纯度,并对真菌多糖的结构分析进行了综述。此外,未来的前景,在这篇综述中可以发现真菌多糖在药物应用中的挑战。总的来说,这篇综述是探索真菌多糖治疗潜力和应用的宝贵资源。通过建立现有的知识库和解决关键的研究差距,研究人员可以找到利用真菌多糖作为有价值的治疗剂和药物功能成分的新机会,营养食品,和生物技术。
    Asian nations have long used edible fungi as food and medicine. Polysaccharides are among the main building units of the cell walls of fungi. Fungal polysaccharides have been documented in the medicinal and industrial sectors as products with a vast array of various biological activities and applications such as antitumor, antioxidant, anticancer, immunomodulation, and antiviral activities, etc. The goal of this review is to give insights into the various biological activities of mushroom polysaccharides and their potential as a medicine for human health. The extraction, purity, and structural analysis of fungal polysaccharides were also reviewed in this work. Also, future prospective, and challenges for fungal polysaccharides in pharmaceutical applications can be found in this review. Overall, this review serves as a valuable resource in exploring the therapeutic potential and applications of fungal polysaccharides. By building upon the existing knowledge base and addressing critical research gaps, researchers can find new opportunities for utilizing fungal polysaccharides as valuable therapeutic agents and functional ingredients in pharmaceuticals, nutraceuticals, and biotechnology.
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  • 文章类型: Journal Article
    多重遗传,环境,和免疫变量导致神经精神疾病(NPDs)。诱导的炎性免疫应答还与各种NPD的严重程度和治疗结果有关。这些反应还通过炎性细胞因子和趋化因子显著影响许多脑功能,例如GABA能信号传导和神经递质合成。查尔酮(1,3-二芳基-2-丙-1-酮)和它们的杂环对应物是具有包括抗炎活性的各种生物学特征的黄酮类化合物。几种纯查耳酮已被临床授权或在人体中研究。由于其微小的分子大小,Chalcones因其在神经炎症中的诊断和治疗功效而受到青睐,易于制造,和灵活性的变化,以调整理想的亲脂性BBB穿透性。这些化合物达到可接受的血浆浓度并且在临床试验中具有良好的耐受性。因此,它们越来越引起科学家的注意。然而,查耳酮的治疗潜力仍未被开发。本文旨在强调神经炎症的原因,更有效的查尔酮同源物,他们的行动机制,和相关的结构-活动关系。
    Multiple genetic, environmental, and immunological variables cause neuropsychiatric disorders (NPDs). The induced inflammatory immune response is also connected to the severity and treatment outcomes of various NPDs. These reactions also significantly impact numerous brain functions such as GABAergic signaling and neurotransmitter synthesis through inflammatory cytokines and chemokines. Chalcones (1,3-diaryl-2-propen-1-ones) and their heterocyclic counterparts are flavonoids with various biological characteristics including anti-inflammatory activity. Several pure chalcones have been clinically authorized or studied in humans. Chalcones are favored for their diagnostic and therapeutic efficacy in neuroinflammation due to their tiny molecular size, easy manufacturing, and flexibility for changes to adjust lipophilicity ideal for BBB penetrability. These compounds reached an acceptable plasma concentration and were well-tolerated in clinical testing. As a result, they are attracting increasing attention from scientists. However, chalcones\' therapeutic potential remains largely untapped. This paper is aimed at highlighting the causes of neuroinflammation, more potent chalcone congeners, their mechanisms of action, and relevant structure-activity relationships.
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  • 文章类型: Journal Article
    由于现有抗真菌药物中出现的耐药性,真菌感染对医疗保健系统构成严重威胁。在临床实践中可用的抗真菌药物中,唑类(二唑,1,2,4-三唑和四唑)仍然是最有效和广泛使用的抗真菌剂。现在,它们相关的副作用和新出现的耐药模式增加了对新的有效抗真菌剂的需求。羊毛甾醇14α-脱甲基酶(CYP51)负责氧化去除甾醇前体羊毛甾醇和24(28)-亚甲基-24,25-二氢羊毛甾醇在麦角甾醇生物合成中的14α-甲基,因此是真菌生命周期的重要组成部分,也是抗真菌药物开发的重要目标。这篇综述将阐明各种基于唑和非唑的衍生物作为靶向真菌CYP51的潜在抗真菌剂。回顾将提供有关结构活动关系的深刻见解,药理学结果,以及衍生物与CYP51在分子水平上的相互作用。它将帮助致力于抗真菌开发的药物化学家设计更合理的,强力,和更安全的抗真菌药物,通过靶向真菌CYP51来解决新出现的抗真菌药物耐药性。
    Fungal infections are posing serious threat to healthcare system due to emerging resistance among available antifungal agents. Among available antifungal agents in clinical practice, azoles (diazole, 1,2,4-triazole and tetrazole) remained most effective and widely prescribed antifungal agents. Now their associated side effects and emerging resistance pattern raised a need of new and potent antifungal agents. Lanosterol 14α-demethylase (CYP51) is responsible for the oxidative removal of 14α-methyl group of sterol precursors lanosterol and 24(28)-methylene-24,25-dihydrolanosterol in ergosterol biosynthesis hence an essential component of fungal life cycle and prominent target for antifungal drug development. This review will shed light on various azole- as well as non-azoles-based derivatives as potential antifungal agents that target fungal CYP51. Review will provide deep insight about structure activity relationship, pharmacological outcomes, and interactions of derivatives with CYP51 at molecular level. It will help medicinal chemists working on antifungal development in designing more rational, potent, and safer antifungal agents by targeting fungal CYP51 for tackling emerging antifungal drug resistance.
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  • 文章类型: Journal Article
    拓扑异构酶(TOPO)在DNA代谢中起着不可或缺的作用,通过调节DNA的拓扑状态。拓扑异构酶I和II是开发抗癌剂和抗生素的公认药物靶标。这些药物靶向酶已用于建立药物刺激的DNA可切割复合物形成与细胞毒性之间的关系。一些抗癌药物(如喜树碱,蒽环类药物,米托蒽醌)也广泛用作TopoI和TopoII抑制剂,但是水溶性差,骨髓瘤抑制,剂量依赖性心脏毒性,和多药耐药性(MDR)限制了它们作为治疗剂的延长使用。此外,这些药物中的大多数仅显示出对TopoI或II的选择性抑制。近年来,研究人员专注于TopoI和II双重抑制剂的设计和合成,或从天然产物中发现TopoI和II双重抑制剂。紫草素(具有蒽醌骨架的天然化合物,从紫草根中分离出来)由于其广泛的抗癌活性而引起了广泛的关注,特别是由于其双重Topo抑制性能,并且没有不良副作用,并合成了不同种类的紫草素衍生物作为TOPO抑制剂,用于开发抗癌剂。在这次审查中,紫草素及其衍生物及其抗癌活性的进展,抗癌机制,通过对CNKI文献的搜索,对它们的结构-活动关系(SAR)进行了全面总结,PubMed,WebofScience,Scopus,和谷歌学者数据库。
    The topoisomerases (TOPO) play indispensable roles in DNA metabolism, by regulating the topological state of DNA. Topoisomerase I and II are the well-established drug-targets for the development of anticancer agents and antibiotics. These drugs-targeting enzymes have been used to establish the relationship between drug-stimulated DNA cleavable complex formation and cytotoxicity. Some anticancer drugs (such as camptothecin, anthracyclines, mitoxantrone) are also widely used as Topo I and Topo II inhibitors, but the poor water solubility, myeloma suppression, dose-dependent cardiotoxicity, and multidrug resistance (MDR) limited their prolong use as therapeutics. Also, most of these agents displayed selective inhibition only against Topo I or II. In recent years, researchers focus on the design and synthesis of the dual Topo I and II inhibitors, or the discovery of the dual Topo I and II inhibitors from natural products. Shikonin (a natural compound with anthraquinone skeleton, isolated from the roots of Lithospermum erythrorhizon) has drawn much attention due to its wide spectrum of anticancer activities, especially due to its dual Topo inhibitive performance, and without the adverse side effects, and different kinds of shikonin derivatives have been synthesized as TOPO inhibitors for the development of anticancer agents. In this review, the progress of the shikonin and its derivatives together with their anticancer activities, anticancer mechanism, and their structure-activity relationship (SAR) was comprehensively summarized by searching the CNKI, PubMed, Web of Science, Scopus, and Google Scholar databases.
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  • 文章类型: Journal Article
    植物五环三萜具有广泛的药理活性,如抗氧化,抗肿瘤,抗微生物和抗炎活性。据信这些生物活性中涉及的机制是由于免疫系统的调节。最近,对来自高等植物的五环三萜的免疫调节的药理学验证非常有限,并且与该组化合物相关的一些现有综述论文尚未集中于该活性。在这次审查中,我们强调了一些关于植物五环三萜的免疫调节潜力的研究,这些植物五环三萜是基于各种临床前的体外和动物模型,从各种不同种类的药用植物和草药中分离出来的。本文还试图讨论与结构-活性关系相关的化合物的生物活性。因此,五环三萜的评估为发现具有有益免疫调节特性的佐剂和新型治疗剂提供了很好的机会。
    Botanical pentacyclic triterpenes possessed a broad range of pharmacological activities such as anti-oxidant, anti-tumor, anti-microbial and anti-inflammatory activities. It is believed that the mechanisms involved in these bioactivities are due to the modulation of immune system. Recently, the pharmacological validation on immunomodulatory of pentacyclic triterpenes derived from higher plants is very limited and several existence review papers related for this group of compound have not been focused for this activity. In this review, we have highlighted several studies on immunomodulatory potential of botanical pentacyclic triterpenes isolated from wide array of different species of medicinal plants and herbs based on various preclinical in vitro and animal models. This review also attempts to discuss on bioactivities of compouns related with their structure-activity relationship. Hence, the evaluation of pentacyclic triterpenes offers a great opportunity to discover adjuvants and novel therapeutic agents that presented beneficial immunomodulatory properties.
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  • 文章类型: Journal Article
    鲍曼不动杆菌,革兰氏阴性,葡萄糖非发酵球菌是造成广泛的机会性医院感染的原因,因此被列为世卫组织“关键优先病原体”,为此,鉴定和开发新的抗菌剂是一个迫切的未满足的医疗需求。当前的综述试图概述各种机制(酶促和非酶促),负责鲍曼不动杆菌抗性的毒力因子。此外,鲍曼不动杆菌的抑制剂分为不同的类别,突出了它们的MDR抑制特性。此外,增强现有抗生素的新型佐剂,以及限制鲍曼不动杆菌感染中生物膜形成的天然和合成化合物。
    Acinetobacter baumannii, a Gram-negative, glucose non-fermentative coccobacilli are responsible for causing a wide range of opportunistic nosocomial infections, thus listed as a WHO \"critical priority pathogen\", for which identification and development of new antibacterial agents are an urgent unmet medical need. The current review attempts to present an overview of various mechanisms (enzymatic and non-enzymatic), virulence factors responsible for A. baumannii resistance. Furthermore, inhibitors of A. baumannii are categorized into different classes highlighting their MDR inhibition properties. In addition, novel adjuvants that potentiate existing antibiotics, as well as natural and synthetic compounds that limit biofilm formation in A. baumannii infections are discussed.
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  • 文章类型: Journal Article
    黄酮类化合物-一类低分子量的次级代谢产物-在整个植物界中普遍存在且聚宝盆。在结构上,主要结构由具有不同取代模式的C6-C3-C6环组成,从而获得许多子类,例如:黄酮醇,黄酮木脂素,类黄酮苷,flavans,花青素,极光,花青素,黄酮,新类黄酮,查尔酮,异黄酮,黄酮和黄烷酮。黄酮类化合物被评估为具有类似药物的性质,因为它们具有不同的治疗活性,可以起到心脏保护作用,抗病毒,抗糖尿病药,抗炎,抗菌,抗癌,还可以对抗阿尔茨海默病和其他疾病。然而,关于它们的结构和生物活性之间关系的信息很少。因此,本综述试图总结黄酮类化合物的所有治疗活性,它们的作用机制和结构活动关系。
    Flavonoids -a class of low molecular weight secondary metabolites- are ubiquitous and cornucopia throughout the plant kingdom. Structurally, the main structure consists of C6-C3-C6 rings with different substitution patterns so that many sub-classes are obtained, for example: flavonols, flavonolignans, flavonoid glycosides, flavans, anthocyanidins, aurones, anthocyanidins, flavones, neoflavonoids, chalcones, isoflavones, flavones and flavanones. Flavonoids are evaluated to have drug like nature since they possess different therapeutic activities, and can act as cardioprotective, antiviral, antidiabetic, anti-inflammatory, antibacterial, anticancer, and also work against Alzheimer\'s disease and others. However, information on the relationship between their structure and biological activity is scarce. Therefore, the present review tries to summarize all the therapeutic activities of flavonoids, their mechanisms of action and the structure activity relationship.
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  • 文章类型: Journal Article
    三萜是根据Ruzicka的异戊二烯规则生物合成的天然存在的衍生物。据报道,三萜具有广泛的治疗应用,包括抗病毒性质。在这次审查中,最近的研究(2010-2020)有关三萜的抗病毒活性进行了总结。已经描述了结构活性关系研究,并讨论了这些三萜的简要生物合成。
    Triterpenes are naturally occurring derivatives biosynthesized following the isoprene rule of Ruzicka. The triterpenes have been reported to possess a wide range of therapeutic applications including anti-viral properties. In this review, the recent studies (2010-2020) concerning the anti-viral activities of triterpenes have been summarized. The structure activity relationship studies have been described as well as brief biosynthesis of these triterpenes is discussed.
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  • 文章类型: Journal Article
    Carbohydrazides and their Schiff bases are important class of heterocycles that are not only employed in the area of organic chemistry, but also have tremendous applications in physical and inorganic chemistry. A series of potential bioactive compounds, containing carbohydrazide functionality and their hydrazone derivatives have been synthesized and screened for antibacterial, anticancer, antifungal and anti-inflammatory etc. This brief review discloses some synthetic route to so many reported carbohydrazides, their Schiff bases, their biological activities and their structure activity relationship.
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