Search results for "DISCOVERY"
showing 10 items of 4119 documents
Lanostanoids from fungi: a group of potential anticancer compounds.
2012
Lanostanes are a group of tetracyclic triterpenoids derived from lanosterol. They have relevant biological and pharmacological properties, such as their cytotoxic effects via induction of apoptosis. This review compiles the most relevant lanostanoids studied from 2000 to 2011, principally those isolated from Ganoderma lucidum and other related fungi, such as Poria cocos, Laetiporus sulphureus, Inonotus obliquus, Antrodia camphorata, Daedalea dickinsii, and Elfvingia applanata, which have great potential as anticancer agents because of their cytotoxic or apoptotic effects. The compounds were selected on the basis of their proapoptotic mechanisms, through their ability to modify transcription…
Antitumor effects of curcumin and structurally β-diketone modified analogs on multidrug resistant cancer cells
2007
Abstract Using concepts of bioisostery a series of curcumin analogs were synthesized: the diketonic system of the compound was elaborated into enaminones, oximes, and the isoxazole heterocycle. The cell growth inhibitory and apoptosis inducing effects of the new analogs were evaluated by in vitro assays in the hepatocellular carcinoma HA22T/VGH cells, as well as in the MCF-7 breast cancer cell line and in its multidrug resistant (MDR) variant MCF-7R. Increased antitumor activity on all cell lines was found with the isoxazole analog and especially with the benzyl oxime derivative; in the HA22T/VGH cell model, the latter compound inhibited constitutive NF-κB activation.
A Bimolecular Multicelular complementation system for the detection of syncytium formation: A new methodology for the identification of entry inhibit…
2019
AbstractFusion of viral and cellular membranes is a key step during the viral life cycle. Enveloped viruses trigger this process by means of specialized viral proteins expressed on their surface, the so called viral fusion proteins. There are multiple assays to analyze the viral entry including those that focus on the cell-cell fusion induced by some viral proteins. These methods often rely on the identification of multinucleated cells (syncytium) as a result of cell membrane fusions. In this manuscript, we describe a novel methodology for the study of cell-cell fusion. Our approach, named Bimolecular Multicelular Complementation (BiMuC), provides an adjustable platform to investigate quali…
Comparative analysis of virtual screening approaches in the search for novel EphA2 receptor antagonists
2015
The EphA2 receptor and its ephrin-A1 ligand form a key cell communication system, which has been found overexpressed in many cancer types and involved in tumor growth. Recent medicinal chemistry efforts have identified bile acid derivatives as low micromolar binders of the EphA2 receptor. However, these compounds suffer from poor physicochemical properties, hampering their use in vivo. The identification of compounds able to disrupt the EphA2-ephrin-A1 complex lacking the bile acid scaffold may lead to new pharmacological tools suitable for in vivo studies. To identify the most promising virtual screening (VS) protocol aimed at finding novel EphA2 antagonists, we investigated the ability of…
Synthesis, spectroscopic studies and biological evaluation of acridine derivatives: The role of aggregation on the photodynamic efficiency.
2018
Two new photoactive compounds (1 and 2) derived from the 9-amidoacridine chromophore have been synthesized and fully characterized. Their abilities to produce singlet oxygen upon irradiation have been compared. The synthesized compounds show very different self-aggregating properties since only 1 present a strong tendency to aggregate in water. Biological assays were conducted with two cell types: hepatoma cells (Hep3B) and human umbilical vein endothelial cells (HUVEC). Photodynamic therapy (PDT) studies carried out with Hep3B cells showed that non-aggregating compound 2 showed photoxicity, ascribed to the production of singlet oxygen, being aggregating compound 1 photochemically inactive.…
Brain and Cancer: The Protective Role of Erythropoietin
2005
Erythropoietin (Epo) is a pleiotropic agent, that is to say, it can act on several cell types in different ways. An independent system Epo/Epo receptor (EpoR) was detected in brain, leading to the hypothesis that this hormone could be involved in cerebral functions. Epo/EpoR expression changes during ontogenesis, thus indicating the importance of this system in neurodevelopment. Moreover, the hypoxia-induced production of Epo in the adult brain suggests that it could exert a neurotrophic and neuroprotective effect in case of brain injury. Epo could also influence neuro- transmission, inducing neurotransmitters (NT) release. Epo therapy in anemic cancer patients is still a controversial issu…
A systematic review of inverse agonism at adrenoceptor subtypes
2020
As many, if not most, ligands at G protein-coupled receptor antagonists are inverse agonists, we systematically reviewed inverse agonism at the nine adrenoceptor subtypes. Except for β3-adrenoceptors, inverse agonism has been reported for each of the adrenoceptor subtypes, most often for β2-adrenoceptors, including endogenously expressed receptors in human tissues. As with other receptors, the detection and degree of inverse agonism depend on the cells and tissues under investigation, i.e., they are greatest when the model has a high intrinsic tone/constitutive activity for the response being studied. Accordingly, they may differ between parts of a tissue, for instance, atria vs. ventricles…
Synthesis and Antitumor Properties of 2,5-Bis(3'-indolyl) thiophenes: Analogues of Marine Alkaloid Nortopsentin
2007
A series of 11 bis-indolylthiophenes of formula I were obtained by cyclization of bis-indole 1,4-diketones using Lawesson''s reagent. Derivs. I (R = OMe, R1 = SO2Ph), I (R = OMe, R1 = Me), I (R = Cl, R1 = Me), and I (R = OMe, R1 = H) were selected to be evaluated in the full panel of about 60 human tumor cell lines derived from nine human cancer cell types and showed antiproliferative activity generally in the micromolar range. The most sensitive cell lines were: CCRF-CEM, MOLT-4, HL60 (TB), and RPMI-8226 of the leukemia subpanel, HT29 and HCC-2998 cell lines of the colon sub-panel, NCI-H522 of the non-small cell lung cancer sub-panel, LOX IMVI of the melanoma sub-panel, and UO-31 of the re…
Klassifikation der Nierenzellkarzinome/Tumoren und ihre Beziehung zum Nephron-Sammelrohrsystem
1990
After a controversial phase of nomenclature (including--among others--the terms "hypernephroma" and "hypernephroid carcinoma") a cytomorphologically defined subtyping of renal cell tumours (adenomas, carcinomas, oncocytomas) is offered, based on new electron microscopical and histochemical observations. These data are in part supported by cytogenetical findings reported in the literature. Phenotypical/histogenetical relations to different parts or cell types, respectively, of the nephron-collecting duct system could be demonstrated. Chromophobe cell carcinoma and oncocytoma exhibit features of the intercalated cells.
Surface Modification of Polysaccharide-Based Nanoparticles with PEG and Dextran and the Effects on Immune Cell Binding and Stimulatory Characteristic…
2017
Surface modifications of nanoparticles can alter their physical and biological properties significantly. They effect particle aggregation, circulation times, and cellular uptake. This is particularly critical for the interaction with primary immune cells due to their important role in particle processing. We can show that the introduction of a hydrophilic PEG layer on the surface of the polysaccharide-based nanoparticles prevents unwanted aggregation under physiological conditions and decreases unspecific cell uptake in different primary immune cell types. The opposite effect can be observed with a parallel-performed introduction of a layer of low molecular weight dextran (3.5 and 5 kDa) on…