Search results for "DISCOVERY"
showing 10 items of 4119 documents
Ovine Carotid Artery-Derived Cells as an Optimized Supportive Cell Layer in 2-D Capillary Network Assays
2014
PLoS one 9(3), e91664 (2014). doi:10.1371/journal.pone.0091664
Heparin–polynitroxide derivatives: a platform for new diagnostic and therapeutic agents in cardiovascular disease?
2013
Vascular wall extracellular oxidative stress Cardiovascular disease (CVD; mainly atherosclerosis, hypertension and diabetes mellitus) remains a major cause of death in western society [1]. Despite substantial progress achieved, the diagnosis of CVD often comes too late, when the disease has already advanced to therapeutically incurable stages. The development of efficient diagnostic probes allowing early non-invasive diagnostics, as well as drugs which can prevent or reverse CVD and/or its complications (e.g., myocardium infarctus and stroke) are highly desired tasks of the modern cardiovascular medicinal chemistry.
Identification and optimization of small molecule antagonists of vasoactive intestinal peptide receptor-1 (VIPR1).
2012
Identification, synthesis and structure-activity relationship of small-molecule VIPR1 antagonists encompassing two chemical series are described.
New Lipid Modulating Drugs: The Role of Microsomal Transport Protein Inhibitors
2011
Microsomal triglyceride transfer protein (MTP) is involved in the synthesis of very low density lipoprotein in the liver. Its deficiency results in abetalipoproteinemia. MTP inhibitors target the assembly and secretion of apolipoprotein B-containing lipoproteins. These agents may potentially play a role, alone or in combination, in the treatment of hypercholesterolemia or hypertriglyceridemia. Clinical applications of MTP inhibitors initially focused primarily on high-dose monotherapy in order to produce substantial reductions in LDL-cholesterol levels but these proved to induce significant hepatic steatosis and transaminase elevations. However, likely orphan indications for MTP inhibitors,…
Responses to eccentric rotation in two space-bound subjects
1993
Two subjects were rotated eccentrically in the manner described previously. In contrast to a normal control group, settings of a luminous line to the subjective vertical were almost unrelated to the gravitoinertial vector before, and totally so shortly after, space flight. Only 3 days postflight did a clear relation to the gravitoinertial vector re-establish itself in the one subject who actually flew. The correspondence became normal 5 days after the flight. Since there were no clinical abnormalities evident in the subjects, it is suggested that both subjects suppressed their vestibular information, presumably as an effect of vestibular deconditioning training before the flight. In additio…
Synthesis of vinca alkaloids and related compounds LX. A simple transformation of apovincamine into vincamine
1992
Abstract The 15α-chloro-vincamine derivative 2 was prepared and proved to be key intermediate of a two-step transformation of apovincamine into vincamine. The structure of 2 was established via detailed NMR and X-ray investigations.
Copper-catalyzed regioselective synthesis of (E)-β-fluorovinyl sulfones
2019
Organofluorine compounds are finding increasing application in a variety of fields such as pharmaceutical, agrochemical, and material sciences. However, given the scarcity of fluorine-containing natural products, advancement in this area depends almost entirely on the development of new synthetic methodologies. In this article, we present the synthesis of a series of previously undescribed (E)-&beta
Comparative Study of Different Methods for the Prediction of Drug–Polymer Solubility
2015
In this study, a comparison of different methods to predict drug-polymer solubility was carried out on binary systems consisting of five model drugs (paracetamol, chloramphenicol, celecoxib, indomethacin, and felodipine) and polyvinylpyrrolidone/vinyl acetate copolymers (PVP/VA) of different monomer weight ratios. The drug-polymer solubility at 25 °C was predicted using the Flory-Huggins model, from data obtained at elevated temperature using thermal analysis methods based on the recrystallization of a supersaturated amorphous solid dispersion and two variations of the melting point depression method. These predictions were compared with the solubility in the low molecular weight liquid ana…
Treatment of Anderson-Fabry Disease
2020
Fabry disease is an X-linked disorder of glycosphingolipid metabolism that results in progressive accumulation of neutral glycosphingolipids, predominantly globotriaosylsphingosine (Gb3) in lysosomes, as well as other cellular compartments of several tissues, causing multi-organ manifestations (acroparesthesias, hypohidrosis, angiokeratomas, signs and symptoms of cardiac, renal, cerebrovascular involvement). Pathogenic mutations lead to a deficiency of the lysosomal enzyme alpha-galactosidase A (GLA). In the presence of high clinical suspicion, a careful physical examination and specific laboratory tests are required. Finally, the diagnosis of Fabry’s disease is confirmed by the demonstrat…
A Molecular Dynamics-Shared Pharmacophore Approach to Boost Early-Enrichment Virtual Screening: A Case Study on Peroxisome Proliferator-Activated Rec…
2016
Molecular dynamics (MD) simulations can be used, prior to virtual screening, to add flexibility to proteins and study them in a dynamic way. Furthermore, the use of multiple crystal structures of the same protein containing different co-crystallized ligands can help elucidate the role of the ligand on a protein's active conformation, and then explore the most common interactions between small molecules and the receptor. In this work, we evaluated the contribution of the combined use of MD on crystal structures containing the same protein but different ligands to examine the crucial ligand-protein interactions within the complexes. The study was carried out on peroxisome proliferator-activat…