drug discover

  • 文章类型: Journal Article
    表面增强拉曼光谱(SERS)是一种非常灵敏的技术,即使在复杂的样品基质中,也可以在极低浓度下检测和鉴定分子和分子结构。由于需要纳米结构的贵金属表面来增强拉曼散射,获得的光谱信息自然来源于纳米尺寸域,使其成为一种通过打破光的衍射极限的纳米光谱技术。在这次审查中,第一拉曼光谱,它与其他相关技术的比较,简要介绍了其工作模式和仪器。然后,SERS机制,讨论了影响SERS实验的衬底和参数。最后,它在制药中的应用,包括药物发现,药物代谢,多功能化学-光热-疗法-递送-释放-成像,对复杂生物样品中的药物稳定性和药物/代谢物检测进行了综述和阐述。
    Surface-enhanced Raman spectroscopy (SERS) is a very sensitive technique offering unique opportunities for detection and identification of molecules and molecular structures at extremely low concentrations even in complex sample matrixes. Since a nanostructured noble metal surface is required for the enhancement of Raman scattering, the acquired spectral information naturally originates from nanometer size domains making it a nanospectroscopic technique by breaking the diffraction limit of light. In this review, first Raman spectroscopy, its comparison to other related techniques, its modes and instrumentation are briefly introduced. Then, the SERS mechanism, substrates and the parameters influencing a SERS experiment are discussed. Finally, its applications in pharmaceuticals including drug discovery, drug metabolism, multifunctional chemo-photothermal-therapy-delivery-release-imaging, drug stability and drug/metabolite detection in complex biological samples are summarized and elaborated.
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  • 文章类型: Journal Article
    The cannabinoid 1 (CB1) receptor regulates appetite and body weight; however, unwanted central side effects of both agonists (in wasting disorders) or antagonists (in obesity and diabetes) have limited their therapeutic utility. At the peripheral level, CB1 receptor activation impacts the energy balance of mammals in a number of different ways: inhibiting satiety and emesis, increasing food intake, altering adipokine and satiety hormone levels, altering taste sensation, decreasing lipolysis (fat break down), and increasing lipogenesis (fat generation). The CB1 receptor also plays an important role in the gut-brain axis control of appetite and satiety. The combined effect of peripheral CB1 activation is to promote appetite, energy storage, and energy preservation (and the opposite is true for CB1 antagonists). Therefore, the next generation of CB1 receptor medicines (agonists and antagonists, and indirect modulators of the endocannabinoid system) have been peripherally restricted to mitigate these issues, and some of these are already in clinical stage development. These compounds also have demonstrated potential in other conditions such as alcoholic steatohepatitis and diabetic nephropathy (peripherally restricted CB1 antagonists) and pain conditions (peripherally restricted CB1 agonists and FAAH inhibitors). This review will discuss the mechanisms by which peripheral CB1 receptors regulate body weight, and the therapeutic utility of peripherally restricted drugs in the management of body weight and beyond.
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  • 文章类型: Journal Article
    The Wnt signaling is one of the major pathways known to regulate embryonic development, tissue renewal and regeneration in multicellular organisms. Dysregulations of the pathway are a common cause of several types of cancer and other diseases, such as osteoporosis and rheumatoid arthritis. This makes Wnt signaling an important therapeutic target. Small molecule activators and inhibitors of signaling pathways are important biomedical tools which allow one to harness signaling processes in the organism for therapeutic purposes in affordable and specific ways. Natural products are a well known source of biologically active small molecules with therapeutic potential. In this article, we provide an up-to-date overview of existing small molecule modulators of the Wnt pathway derived from natural products. In the first part of the review, we focus on Wnt pathway activators, which can be used for regenerative therapy in various tissues such as skin, bone, cartilage and the nervous system. The second part describes inhibitors of the pathway, which are desired agents for targeted therapies against different cancers. In each part, we pay specific attention to the mechanisms of action of the natural products, to the models on which they were investigated, and to the potential of different taxa to yield bioactive molecules capable of regulating the Wnt signaling.
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  • 文章类型: Journal Article
    慢性金黄色葡萄球菌感染不仅由对常规抗生素的耐药性发展而频繁复发,而且还通过形成持久的细菌细胞。细菌的持久性是短暂的,代谢不活跃状态,使针对基本细胞生长过程的常规抗生素无效,导致抗生素化疗的高临床失败率。开发针对持久性金黄色葡萄球菌的新抗生素是一个紧迫的问题。在过去的十年里,已经提出了鉴定金黄色葡萄球菌持久活性化合物的新策略。这篇综述总结了拟议的目标,抗衰老化合物和创新的方法,可以增强常规抗生素对金黄色葡萄球菌的持久性。经过审查的抗压战略可以概括为两大类;直接瞄准与增长无关的目标,增强现有的,通过帮助吸收或可及性而无效的抗生素。
    Chronic Staphylococcus aureus infections are complicated by frequent relapses not only from the development of drug resistance to conventional antibiotics, but also through the formation of persister bacterial cells. Bacterial persisters are in a transient, metabolically inactive state, making conventional antibiotics that target essential cellular growth processes ineffective, resulting in high clinical failure rates of antibiotic chemotherapy. The development of new antibiotics against persistent S. aureus is an urgent issue. Over the last decade, new strategies to identify S. aureus persister-active compounds have been proposed. This review summarizes the proposed targets, antipersister compounds and innovative methods that may augment conventional antibiotics against S. aureus persisters. The reviewed antipersister strategies can be summarized as two broad categories; directly targeting growth-independent targets and potentiating existing, ineffective antibiotics by aiding uptake or accessibility.
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  • 文章类型: Journal Article
    Invasive candidiasis continues to be associated with significant morbidity and mortality as well as substantial health care costs nationally and globally. One of the contributing factors is the development of resistance to antifungal agents that are already in clinical use. Moreover, there are known treatment limitations with all of the available antifungal agents. Since traditional techniques in novel drug discovery are time consuming, high-throughput screening using flow cytometry presents as a potential tool to identify new antifungal agents that would be useful in the management of these patients. Areas covered: In this review, the authors discuss the use of automated high-throughput screening assays based upon flow cytometry to identify potential antifungals from a library comprised of a large number of bioactive compounds. They also review studies that employed the use of this research methodology that has identified compounds with antifungal activity. Expert opinion: High-throughput screening using flow cytometry has substantially decreased the processing time necessary for screening thousands of compounds, and has helped enhance our understanding of fungal pathogenesis. Indeed, the authors see this technology as a powerful tool to help scientists identify new antifungal agents that can be added to the clinician\'s arsenal in their fight against invasive candidiasis.
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