Search results for "Indole"
showing 10 items of 570 documents
Geldanamycin and its derivatives as Hsp90 inhibitors
2012
The Hsp90 molecule, one of the most abundant heat shock proteins in mammalian cells, maintains homeostasis and prevents stress-induced cellular damage. Hsp90 is expressed under normal conditions at a level of about 1-2 Percent of total proteins, while its expression increases 2-10 fold in cancer cells. The two main constitutively expressed isoforms of Hsp90 are known as Hsp90-alpha and Hsp90-beta, and their upregulation is associated with tumor progression, invasion and formation of metastases, as well as development of drug resistance. The Hsp90 is a key target for many newly established, potent anticancer agents containing Hsp90 N-terminal ATP binding inhibitors, such as geldanamycin, and…
Intrinsic fluorescence of the clinically approved multikinase inhibitor nintedanib reveals lysosomal sequestration as resistance mechanism in FGFR-dr…
2017
Background Studying the intracellular distribution of pharmacological agents, including anticancer compounds, is of central importance in biomedical research. It constitutes a prerequisite for a better understanding of the molecular mechanisms underlying drug action and resistance development. Hyperactivated fibroblast growth factor receptors (FGFRs) constitute a promising therapy target in several types of malignancies including lung cancer. The clinically approved small-molecule FGFR inhibitor nintedanib exerts strong cytotoxicity in FGFR-driven lung cancer cells. However, subcellular pharmacokinetics of this compound and its impact on therapeutic efficacy remain obscure. Methods 3-dimens…
Harnessing medically relevant metals onto water-soluble subphthalocyanines: towards bimodal imaging and theranostics
2014
International audience; Subphthalocyanine (SubPc), a putative fluorophore for optical imaging (OI), was conjugated to chelating ligands (DOTA, DTPA) affording water-soluble conjugates complexed with (non-radioactive) metals relevant to the following medical imaging techniques/therapies: MRI (Gd), PET (Cu, Ga), SPECT (In, Ga, Lu), RIT (Cu, Lu, Y), and NCT (Gd). Magneto-optical properties of ditopic gadolinium species (and optical properties of other metal containing species) were examined (brightness (ε × Φ F) and relaxivity R 1) and fluorescence confocal/biphoton microscopy studies were conducted. † Electronic supplementary information (ESI) available: Experimental characterization, NMR and…
Total Synthesis of Phenanthroindolizidine Alkaloids by Combining Iodoaminocyclization with Free Radical Cyclization
2016
A concise and modular synthesis of phenanthroindolizidine alkaloids was achieved by combining iodoaminocylization with a free radical cyclization approach. The route described allowed the preparation of (±)-tylophorine, (±)-antofine, and (±)-deoxypergularinine in six steps. When commercially available l-prolinol was used as a chiral building block, (S)-(+)-tylophorine was also synthesized in 49% yield and >99% ee over five linear steps.
Indole Diterpenoids from an Endophytic Penicillium sp.
2019
A chemical investigation of the endophyte Penicillium sp. (strain ZO-R1-1), isolated from roots of the medicinal plant Zingiber officinale, yielded nine new indole diterpenoids (1-9), together with 13 known congeners (10-22). The structures of the new compounds were elucidated by 1D and 2D NMR analysis in combination with HRESIMS data. The absolute configuration of the new natural products 1, 3, and 7 was determined using the TDDFT-ECD approach and confirmed for 1 by single-crystal X-ray determination through anomalous dispersion. The isolated compounds were tested for cytotoxicity against L5178Y, A2780, J82, and HEK-293 cell lines. Compound 1 was the most active metabolite toward L5178Y ce…
Solid-State Pyrolyses of Metal Phthalocyanines: A Simple Approach towards Nitrogen-Doped CNTs and Metal/Carbon Nanocables
2006
Solid-state pyrolysis of organometallic precursors has emerged as an alternative method for preparing carbon nanostructures such as carbon nanotubes (CNT) and carbon anions. The morphology of the tubes can be controlled by the nature of the precursors and the pyrolysis procedures, and micrometer long nanotubes, composed of metal carbide wires encased in a graphitic sheath. Cobalt phthalocyanine (CoPc) as well as iron phthalocyanine were pyrolyzed at different temperatures to obtain CNTs. HRTEM and energy-dispersion X-Ray analysis disclosed that the core consisted of long, iron-containing single crystals and that the core was fully surrounded by crystallized graphic carbon. Iron-filled carbo…
Synthesis and in Vitro Evaluation of Biotinylated RG108: A High Affinity Compound for Studying Binding Interactions with Human DNA Methyltransferases
2006
Small-molecule inhibitors of DNA methyltransferases such as RG108 represent promising candidates for cancer drug development. We report the synthesis and in vitro analysis of a biotinylated RG108 conjugate, 2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(5-[3-[5-(2-oxo-hexahydro-thieno[3,4-d]imidazol-4-yl)pentanoylamino]propoxy]-1H-indol-3-yl)propionic acid (bio-RG108), for the evaluation of interactions with DNA methyltransferase enzymes. The structural design of the chemically modified inhibitor was aided by molecular modeling, which suggested the possibility for extensive chemical modifications at the 5-position of the tryptophan moiety in RG108. The inhibitory activity of the corresponding d…
Genome size and chromosomes in marine sponges [Suberites domuncula, Geodia cydonium]
1995
The genome size of the marine sponges Suberites domuncula and Geodia cydonium has been determined by flow cytofluorometric analysis using diamidino-phenylindole [DAPI]. Using human lymphocytes as reference the amount of DNA in cells from S. domuncula has been determined to be 3.7 pg and that of G. cydonium 3.3 pg. While no chromosomes could be identified in G. cydonium, the karyotype of the Suberites domuncula is 32 chromosomes in the diploid state. The size of the chromosomes was between 0.25 and 1.0 micron. No pronounced banding pattern was visible.
Fluvastatin stabilizes the blood–brain barrier in vitro by nitric oxide-dependent dephosphorylation of myosin light chains
2006
Inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme-A reductase and the downstream mevalonate pathway is in part responsible for the beneficial effects that statins exert on the cardiovascular system. In this study we aimed at analysing the stabilizing effects of fluvastatin on the blood-brain barrier (BBB) integrity, using an in vitro co-culture model of ECV304 and C6, or primary bovine endothelial cells and rat astrocytes. Fluvastatin dose-dependently (1-25 micromol/l) increased barrier integrity as analysed by measurements of transendothelial electrical resistance (TEER). This effect (117.4+/-2.6% at 25 micromol/l) was significantly reduced by the nitric oxide (NO) synthase inhibitor L…
Fluvastatin prevents glutamate-induced blood-brain-barrier disruption in vitro.
2008
Abstract Glutamate is an important excitatory amino acid in the central nervous system. Under pathological conditions glutamate levels dramatically increase. Aim of the present study was to examine whether the HMG-CoA inhibitor fluvastatin prevents glutamate-induced blood-brain-barrier (BBB) disruption. Measurements of transendothelial electrical resistance (TEER) were performed to analyze BBB integrity in an in vitro co-culture model of brain endothelial and glial cells. Myosin light chain (MLC) phosphorylation was detected by immunohistochemistry, or using the in-cell western technique. Intracellular Ca 2+ and reactive oxygen species (ROS) levels were analyzed using the fluorescence dyes …