Search results for " Disc"
showing 10 items of 9209 documents
Biased Agonism in Drug Discovery—Is It Too Soon to Choose a Path?
2018
A single receptor can activate multiple signaling pathways that have distinct or even opposite effects on cell function. Biased agonists stabilize receptor conformations preferentially stimulating one of these pathways, and therefore allow a more targeted modulation of cell function and treatment of disease. Dedicated development of biased agonists has led to promising drug candidates in clinical development, such as the G protein-biased µ opioid receptor agonist oliceridine. However, leveraging the theoretical potential of biased agonism for drug discovery faces several challenges. Some of these challenges are technical, such as techniques for quantitative analysis of bias and development …
Effects of Chronic Dopamine D2R Agonist Treatment and Polysialic Acid Depletion on Dendritic Spine Density and Excitatory Neurotransmission in the mP…
2016
Dopamine D2 receptors (D2R) in the medial prefrontal cortex (mPFC) are key players in the etiology and therapeutics of schizophrenia. The overactivation of these receptors contributes to mPFC dysfunction. Chronic treatment with D2R agonists modifies the expression of molecules implicated in neuronal structural plasticity, synaptic function, and inhibitory neurotransmission, which are also altered in schizophrenia. These changes are dependent on the expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-related molecule, but nothing is known about the effects of D2R and PSA-NCAM on excitatory neurotransmission and the structure of mPFC pyramidal n…
27Al NMR Study of the pH Dependent Hydrolysis Products of Al2(SO4)3 in Different Physiological Media
2018
Soluble inorganic aluminium compounds like aluminium sulfate or aluminium chloride have been challenged by the European Chemical Agency to induce germ cell mutagenicity. Before conducting mutagenicity tests, the hydrolysis products in water and in physiological solutions should be determined as a function of the concentration and pH. We used different 27Al NMR spectroscopic techniques (heteronuclear Overhauser effect spectroscopy (HOESY), exchange spectroscopy (EXSY), diffusion ordered (DOSY)) in this work to gain the information to study the aluminium species in solutions with Al2(SO4)3 concentrations of 50.0, 5.0, and 0.5 g/L and their pH and time dependent transformation. At low pH, thre…
Magnesium Status in Alzheimer's Disease: A Systematic Review
2016
The interest in poor magnesium (Mg) status as risk factor for Alzheimer's disease (AD) is increasing due to its antioxidant and neuroprotective properties. A systematic PubMed literature search of studies investigating Mg status was undertaken comparing AD to healthy controls (HCs) or patients with medical illness (medical controls [MCs]). Standardized mean differences (SMDs) ± 95% confidence intervals (CIs) were calculated for all outcomes. Of 192 potentially eligible studies, 13 were included (559 patients with AD, 381 HCs, and 126 MCs). Compared to HCs, patients with AD had significantly lower Mg in cerebrospinal fluid (2 studies; SMD = -0.35; P =.02) and in hair (2 studies; SMD = -0.75;…
New Target Sites for Treatment of Osteoporosis
2017
In the last few years, much progress has been achieved in the discovery of new drug target sites for treatment of osteoporotic disorders, one of the main challenging diseases with a large burden for the public health systems. Among these new agents promoting bone formation, shifting the impaired equilibrium between bone anabolism and bone catabolism in the direction of bone synthesis are inorganic polymers, in particular inorganic polyphosphates that show strong stimulatory effects on the expression of bone anabolic marker proteins and hydroxyapatite formation. The bone-forming activity of these polymers can even be enhanced by combination with certain small molecules like quercetin, or if …
New Pharmacological Opportunities for Betulinic Acid
2017
AbstractBetulinic acid is a naturally occurring pentacyclic lupane-type triterpenoid usually isolated from birch trees, but present in many other botanical sources. It is found in different plant organs, both as a free aglycon and as glycosyl derivatives. A wide range of pharmacological activities has been described for this triterpenoid, including antiviral and antitumor effects. In addition, several other interesting properties have been identified in the fields of immunity and metabolism, namely antidiabetic, antihyperlipidemic, and anti-inflammatory activities. Taken together, these latter three properties make betulinic acid a highly interesting prospect for treating metabolic syndrome…
Ziziphora tenuior L. essential oil from Dana Biosphere Reserve (Southern Jordan); chemical characterization and assessment of biological activities
2016
Abstract Ethnopharmacologic relevance Ziziphora tenuior L. (Lamiaceae) is a medicinal plant in Jordan, which is included in various antimicrobial, antiseptic, expectorant and wound healing preparations. It is used for the treatment of cough, stomach ache, dysentery, fever, uterus infection, gut inflammation and painful menstruation. Aim of the study The aim of this study was to assess, for the first time, the chemical composition of the essential oil of Z. tenuior originated from southern Jordan and its antifungal effects against several yeasts. Concomitantly, the mechanisms behind the anti-fungal activity against Candida albicans were also disclosed. Since the Z. tenuior traditional uses a…
Biological activities of polyphenols-enriched propolis from Argentina arid regions
2015
Background: Propolis is a bioactive natural product collected by honeybees (Apis mellifera) fromplant sources. Purpose: This studywas undertaken to determine the effect of propolis extracts from arid region of Argentina, on the activity/expression of pro-inflammatory enzymes, and as potential free radical scavenger, antifungal and anthelmintic agent as well as to get a first insight into the polyphenolic profile of the active fractions.Study design/methods: Two propolis samples were collected in different time from hives located in Tucumán, Argentina. They are representative of the collection time of the raw material for phytotherapeutical purposes. Ethanolic extracts from both propolis wer…
Bridged Epipolythiodiketopiperazines from Penicillium raciborskii, an Endophytic Fungus of Rhododendron tomentosum Harmaja
2016
Three new epithiodiketopiperazine natural products [outovirin A (1), outovirin B (2), and outovirin C (3)] resembling the antifungal natural product gliovirin have been identified in extracts of Penicillium raciborskii, an endophytic fungus isolated from Rhododendron tomentosum. The compounds are unusual for their class in that they possess sulfide bridges between α- and β-carbons rather than the typical α-α bridging. To our knowledge, outovirin A represents the first reported naturally produced epimonothiodiketopiperazine, and antifungal outovirin C is the first reported trisulfide gliovirin-like compound. This report describes the identification and structural elucidation of the compounds…
Synthesis and antitumor activities of 1,2,3-triazines and their benzo- and heterofused derivatives
2017
1,2,3-Triazines are a class of biologically active compounds that exhibit a broad spectrum of activities, including antibacterial, antifungal, antiviral, antiproliferative, analgesic and anti-inflammatory properties. This review, which covers the literature from the end of last century to 2016, treats, through a comprehensive, systematic approach, the 1,2,3-triazine and related benzo- and hetero-fused derivatives possessing antitumor activity. Their efficacy, combined with a simple synthesis confers to these molecules a great potential as scaffold for the development of antitumor compounds.