Search results for "quinolines"
showing 10 items of 182 documents
Optimization of a LC method for the enantioseparation of a non-competitive glutamate receptor antagonist, by experimental design methodology
2006
Abstract The aim of this work was to obtain the direct optical resolution of a new glutamate receptor antagonist (( p -chloro)1-aryl-6,7,-dimethoxy-1,2,3,4-tetrahydroisoquinoline, PS3), by liquid chromatography on Chiralcel ® OD column. A response surface methodology (RSM) was employed to optimize the enantiomeric separation of the racemate with the lowest number of experiments; in particular, a face-centred design (FCD) was applied to evaluate the influence of critical parameters on the experimental response. Furthermore, in order to find the best compromise between several responses, a multicriteria decision-making approach, the Derringer's desirability function, was successful to simulta…
Effect of LIF-withdrawal on acetylcholine synthesis in the embryonic stem cell line CGR8 is not mediated by STAT3, PI3Ks or cAMP/PKA pathways.
2015
Acetylcholine (ACh) acts as a local cellular signaling molecule and is widely expressed in nature, including mammalian cells and embryonic stem cells. The murine embryonic stem cell line CGR8 synthesizes and releases substantial amounts of ACh. Particularly during early differentiation - a period associated with multiple alterations in geno-/phenotype functions - synthesis and release of ACh are increased by 10-fold. In murine stem cells second messengers of the STAT-3, PI3K and cAMP/PKA pathways are involved in maintaining self-renewal and pluripotency. The present experiments were designed to test whether blockers of these signaling pathways enhance ACh cell content in the presence of LIF…
Triazolopyridines 23.1 Synthesis of 5,5'-bi[1,2,3]triazolo[5,1-a]isoquinoline
2004
5,5'-Bi[1,2,3]triazolo[5,1-a]isoquinoline 6 has been synthesised from [1,2,3]triazolo[5,1-a] isoquinoline 5 by four procedures, dimerisation by LDA, Stille and Suzuki self-coupling reactions, and Suzuki cross-coupling reaction. The last is the best. Compound 6 gives 1,1'- bi(acetoxymethyl)-3,3'-biisoquinoline 10 by triazolo ring opening by acetic acid. Abarca Gonzalez, Belen, Belen.Abarca@uv.es ; Ballesteros Campos, Rafael, Rafael.Ballesteros@uv.es ; Gay Roig, Bernat, bergay@alumni.uv.es
NOVEL ANTAGONISTS FOR AN Hsp60-BASED ANTICANCER CHAPERONOTHERAPY
2012
The Heat shock proteins (Hsps) are nowadays considered the most important cell chaperones, which result overexpressed in response to a number of cell stress stimuli.In tumor cells, when Hsp60 accumulates in the cytosol, without mitochondrial release, it exerts an anti-apoptotic effect, by inhibiting pro-caspase-3 (pC3) activation. In this context, our study aims to elucidate the structural details of the interaction between Hsp60 and pC3 and to design novel antagonists able to specifically block this interaction. The analysis of virtual screening results highlights the 4-(3-chloro-4-fluorophenylamino)- 6-[(1H-imidazol-4-yl-methyl)-3-carbonitrile-quinolines of type 1 and the N-{5-[1H-imidazo…
UV Exposure Boosts Transcutaneous Immunization and Improves Tumor Immunity: Cytotoxic T-Cell Priming through the Skin
2010
Immunologic approaches to combat cancer aim at the induction of tumor-reactive immune responses to achieve long-term protection. In this context, we recently developed a transcutaneous immunization (TCI) method using the Toll-like receptor (TLR) 7 agonist imiquimod and a peptide epitope. Application onto intact skin induces potent cytotoxic T lymphocyte (CTL) responses and protection against transplanted tumors. The purpose of this study was to explore the effects of UV irradiation on imiquimod-based TCI. Here we show that skin exposure to low-dose UV light before TCI with imiquimod strongly boosts specific CTL responses leading to memory formation and enhanced tumor protection. Toward the …
N-Heterocyclic choline analogues based on 1,2,3,4-tetrahydro(iso)quinoline scaffold with anticancer and anti-infective dual action
2016
Pharmacological effects of biologically active “small molecules” can be improved by their targeted modification, which affects drug delivery and interaction with tumor cells and microorganisms. We aimed to evaluate anticancer and antimicrobial activity of lipid-like choline derivatives modified via simultaneous introduction of tetrahydro(iso)quinoline based pharmacophore system at nitrogen atom and long chain alkyl substituent at oxygen atom. Target compounds were synthesized under phase-transfer catalysis conditions followed by quaternization, and evaluated for cytotoxicity and NO-generation ability on HT-1080 and MG-22A tumor cell lines and NIH 3T3 normal mouse fibroblasts, and screened f…
Beyond Pseudo‐natural Products: Sequential Ugi/Pictet‐Spengler Reactions Leading to Steroidal Pyrazinoisoquinolines That Trigger Caspase‐Independent …
2021
In this work, we describe how stereochemically complex polycyclic compounds can be generated by applying a synthetic sequence comprising an intramolecular Ugi reaction followed by a Pictet-Spengler cyclization on steroid-derived scaffolds. The resulting compounds, which combine a fragment derived from a natural product and a scaffold not found in nature. are both structurally distinct and globally similar to natural products at the same time, and interrogate an alternative region of the chemical space. One of the new compounds showed significant antiproliferative activity on HepG2 cells through a caspase-independent cell-death mechanism, an appealing feature when new antitumor compounds are…
Regioselective substitution of 6,7-dichloroquinoline-5,8-dione: synthesis and X-ray crystal structure of 4a,10,11-triazabenzo[3,2-a]fluorene-5,6-dion…
2003
6,7-Dichloroquinoline-5,8-dione (1) was reacted with a number of 2-aminopyridine derivatives. Of the several possible products of this reaction, 4a,10,11-triazabenzo[3,2-a]fluorene-5,6-dione (6), produced by condensation and rearrangement, was obtained as the major product, and its structure was subsequently unambigously determined by X-ray crystallographic study. Ortho-quinones were produced via nucleophilic substitution at position C7, which was unexpected, considering that para-quinones were produced via C6 substitution in the reaction between compound 1 and ethyl acetoacetate in our previous work. Such unexpected nucleophilic substitution at C7 provides an effective, yet simple route, t…
Synthesis and cytotoxicity of 6,11-Dihydro-pyrido- and 6,11-Dihydro-benzo[2,3-b]phenazine-6,11-dione derivatives
2003
6,11-Dihydro-pyrido[2,3-b]phenazine-6,11-diones and 6,11-dihydro-benzo[2,3-b]phenazine-6,11-diones were synthesized from 6,7-dichloro-5,8-quinolinedione and 2,3-dichloro-1,4-naphthoquinone. The study on the cytotoxicity on these products revealed that the pyridophenazinediones, tetracyclic heteroquinone analogues with three nitrogen atoms exhibited a high cytotoxicity on several human tumor cell lines. Compound 9c and 9e showed in vitro antitumor activity comparable or superior to doxorubicin against the human ovarian tumor cells (SK-OV-3) and the human CNS cells (XF 498). The IC(50) value for compound 9e was 0.06 microM against the human CNS cells (XF 498), which was 2.6 times higher than …
Crystal structure of [Cu(N-quinolin-8-yl-p-toluenesulfonamidate)2]: study of its interaction with DNA and hydrogen peroxide
2001
A new copper complex with N-quinolin-8-yl-p-toulenesulfonamide has been prepared and characterised. The compound crystallises in the triclinic system, space group P1, with a=13.457(3), b=15.067(5), c=18.589(3) A; α=112.05(2), β=93.92(2), γ=108.30(2)° and Z=4. The geometry of the Cu(II) ion is distorted square planar. The N-quinolin-8-yl-p-toulenesulfonamidate anion behaves as a bidentate ligand through the N s u l f o n a m i d a t e and N q u i n o l i n e atoms. The complex does not cleave DNA in the presence of hydrogen peroxide.