Search results for "Indole"
showing 10 items of 570 documents
Induction of cholesterol biosynthesis by archazolid B in T24 bladder cancer cells.
2014
Abstract Background Resistance of cancer cells towards chemotherapeutics represents a major cause of therapy failure. The objective of our study was to evaluate cellular defense strategies in response to the novel vacuolar H+-ATPase inhibitor, archazolid B. Experimental approach: The effects of archazolid B on T24 bladder carcinoma cells were investigated by combining “omics” technologies (transcriptomics (mRNA and miRNA) and proteomics). Free cholesterol distribution was determined by filipin staining using flow cytometry and fluorescence microscopy. Flow cytometry was performed for LDLR surface expression studies. Uptake of LDL cholesterol was visualized by confocal microscopy. SREBP acti…
Photochemical electrocyclisation of 3-vinylindoles to pyrido[2,3-a]-, pyrido[4,3-a]- and thieno[2,3-a]-carbazoles: Design, synthesis, DNA binding and…
2009
In the context of the design and synthesis of DNA ligands, some new hetarene annelated carbazoles were synthesized. As lead structure the intercalating tetracyclic systems pyrido[2,3-a]- and pyrido[4,3-a]-carbazoles and in one case a thieno[2,3-a]-carbazole were taken into account. A dialkyl amino amidic chain was introduced to the planar chromophoric system with the intent to generate minor groove binding properties. The cytotoxicity of some compounds was examined by the NCI antitumor screening. Furthermore, biophysical as well as biochemical studies were performed in order to get some information about the DNA-binding properties and inhibition of DNA related functional enzymes of this new…
SYNTHESIS AND PHOTOCHEMIOTHERAPEUTIC ACTIVITY OF THIOPYRANO[2,3-E]INDOL-2-ONES
2004
A series of derivatives of the new ring system thiopyrano[2,3-e]indol-2-one was prepared with the aim of obtaining new photochemotherapeutic drugs. Biological screenings were performed on this new class of photoactivable drugs and a strong antiproliferative effect was observed upon irradiation with UVA light. The compound bearing a methyl substituent at the pyrrole nitrogen resulted as the most interesting showing IC50 in the nanomolar range.
Getting new bronchodilator compounds from molecular topology.
2003
Abstract Molecular topology has been used to select new lead bronchodilator compounds. The main advantage of this method, as compared to others frequently used, is that it does not require a previous explicit knowledge of the mechanism of action (MOA) of the compounds analyzed. A large database (12,000 chemicals) has been examined in this study to find less than 5% compounds with bronchodilator activity. After removing those compounds already described as bronchodilators, we present here the results for 20 among these compounds, some of them showing other pharmacological activities. Some of the compounds selected in this study showed higher relaxation and higher potency than theophylline, w…
Isoindolo[2,1-c]benzo[1,2,4]triazines: a new ring system with antiproliferative activity.
2006
Abstract A series of isoindolo-benzo-triazines of type 4 was obtained by diazotization of 2-(2-aminoaryl)-1-cyanoisoindoles 3a – j . All the synthesized derivatives were screened by the National Cancer Institute (NCI, Bethesda, USA), for in vitro antitumor activity against a 3-human cancer cell line panel consisting of MCF7 (breast), NCI-H460 (lung), and SF-268 (CNS). Derivatives 4a , f , i , j were selected to be evaluated in the full panel of about 50 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: MOLT-4 and SR of the leukemia subpanel, A549/ATCC and EKVX of the n…
Chemical profiling of the synthetic cannabinoid MDMB-CHMICA: Identification, assessment, and stability study of synthesis-related impurities in seize…
2019
In this work, the most discriminating synthesis-related impurities found in samples from seizures and controlled synthesis of the synthetic cannabinoid MDMB-CHMICA (methyl (S)-2-(1-(cyclohexylmethyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate) were characterized. Based on 61 available powder samples of MDMB-CHMICA, 15 key-impurities were assessed, isolated in larger quantities via flash chromatography and structurally elucidated and characterized via high resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Apart from verifying the relation of the impurities to the major component, the interpretation of their chemical structures with distinct structural elements pro…
3-[4-(1H-indol-3-yl)-1,3-thiazol-2-yl]-1H-pyrrolo[2,3-b]pyridines, nortopsentin Analogues with antiproliferative activity
2015
A new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and the indole unit bound to position 2 of the thiazole ring was substituted by a 7-azaindole moiety, was efficiently synthesized. Two of the new nortopsentin analogues showed good antiproliferative effect against the totality of the NCI full panel of human tumor cell lines (~60) having GI50 values ranging from low micromolar to nanomolar level. The mechanism of the antiproliferative effect of these derivatives, investigated on human hepatoma HepG2 cells, was pro-apoptotic, being associated with externalization of plasma membrane phosphatidylserine and mitochondrial dysfunctio…
Synthesis of Functionalized Indoles with a Trifluoromethy-Substituted Stereogenic Tertiary Carbon Atom Through an Enantioselective Friedel-Crafts Alk…
2010
[EN] Chiral complexes of BINOL-based ligands with zirconium tert-butoxide catalyze the Friedel-Crafts alkylation reaction of indoles with beta-trifluoromethyl-alpha,beta-unsaturated ketones to give functionalized indoles with an asymmetric tertiary carbon center attached to a trifluoromethyl group. The reaction can be applied to a large number of substituted alpha-trifluoromethyl enones and substituted indoles. The expected products were obtained with good yields and ees of up to 99%.
Validation of Dissolution Testing with Biorelevant Media: An OrBiTo Study.
2017
Dissolution testing with biorelevant media has become widespread in the pharmaceutical industry as a means of better understanding how drugs and formulations behave in the gastrointestinal tract. Until now, however, there have been few attempts to gauge the reproducibility of results obtained with these methods. The aim of this study was to determine the interlaboratory reproducibility of biorelevant dissolution testing, using the paddle apparatus (USP 2). Thirteen industrial and three academic laboratories participated in this study. All laboratories were provided with standard protocols for running the tests: dissolution in FaSSGF to simulate release in the stomach, dissolution in a singl…
Organocatalytic Enantioselective Friedel–Crafts Aminoalkylation of Indoles in the Carbocyclic Ring
2016
The first general catalytic method for the, so far elusive, enantioselective Friedel−Crafts functionalization of indoles in the carbocyclic ring is presented. This transformation contrasts with the usual tendency of these heterocycles to react at the azole ring. For this purpose, the four regioisomeric hydroxy carbocyclic-substituted indoles were reacted with several isatinderived ketimines, using a Cinchona alkaloid-based squaramide, in a low 0.5−5 mol % catalyst loading, as a bifunctional catalyst. This methodology allows the functionalization of indoles in every position of the carbocyclic ring in a regio- and enantioselective fashion, by switching only the position of the hydroxy group …