Search results for "amides"

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…

Chemical Modification of Carbon Nanotubes with Sulfonylamides

Significance of Autologous Interleukin-6 Production in the HA22T/VGH Cell Model of Hepatocellular Carcinoma

2006

Cancer cells may often support their own growth, survival, and drug resistance by autocrine/paracrine loops based on the production of different factors; results from us and others have shown that similar interleukin-6 (IL-6)-related loops are operative in multiple myeloma and prostate or renal cancer. Because this aspect has not been investigated in detail for hepatocellular carcinoma (HCC), we have examined it in HA22T/VGH cells. These differ from other primary liver cancer cell lines (that is, HepG2, HuH-6, and HuH-7) in that enzyme-linked immunosorbent assay (ELISA) showed the HA22T/VGH cells to secrete remarkable amounts of IL-6 (16.8 ng/10(6) cells/24 h); this production, due to const…

Neural cell pattern formation on glass and oxidized silicon surfaces modified with poly(N-isopropylacrylamide)

1996

Control over the adsorption of proteins and over the adsorption and spatial orientation of mammalian cells onto surfaces has been achieved by modification of glass and other silicon oxide substrates with poly(N-isopropylacrylamide) (PNIPAM). The functionalization of the substrates was achieved either by a polymer-analogous reaction of aminosilanes with reactive N-(isopropylacrylamide) (NIPAM)-copolymers and by copolymerization of NIPAM with surface-bound methacrylsilane. The obtained coatings were characterized by FT-1R, ellipsometry, and surface plasmon resonance measurements. The adsorption of two proteins-fibrinogen and ribonuclease A-on these surfaces was studied in situ by real time su…

Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-1)…

2014

Although the addition of the HCV NS3/4A protease inhibitors boceprevir and telaprevir to pegylated interferon (peginterferon) alfa plus ribavirin has improved sustained virological response (SVR) in treatment-naive and treatment-experienced patients infected with hepatitis C virus (HCV) genotype 1, the regimens have a high pill burden and are associated with increased rates and severity of adverse events, such as anaemia and rash. The efficacy and safety of the combination of simeprevir, a one pill, once-daily, oral HCV NS3/4A protease inhibitor, plus peginterferon alfa 2a plus ribavirin were assessed in treatment-naive patients with HCV genotype 1 infection.In QUEST-1, a phase 3, randomise…

The clinical relevance of low-density-lipoproteins size modulation by statins.

2006

The predominance of small, dense low density lipoproteins (LDL) has been accepted as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III; in fact, LDL size seems to be an important predictor of cardiovascular events and progression of coronary heart disease. Several studies have also shown that the therapeutical modulation of LDL size is of great benefit in reducing the risk of cardiovascular events. Hypolipidemic treatment is able to alter LDL subclass distribution and statins are currently the most widely used lipid-lowering agents. Statins are potent inhibitors of hydroxy-methyl-glutaryl-coenzyme A reductase, the rate-limiting en…

The influence of Span®20 on stratum corneum lipids in Langmuir monolayers: comparison with Azone®

2000

Recently we have proved that Span 20 has the same enhancer effect as Azone on in vitro percutaneous penetration of lipophilic compounds (logP(oct) from 1.34 to 2.33). The purpose of this work is to study the interactions of Span 20 with stratum corneum lipids monolayers and to compare them with Azone. The surface pressure-area characteristics of Span 20 in mixed monolayers with different model lipids (ceramides, cholesterol, free fatty acids and two mixtures of ceramides+cholesterol, and ceramides+cholesterol+free fatty acids) in similar proportions to that which exists in human stratum corneum lipids were recorded as compression isotherms at 25 degrees C. Azone was also investigated on mon…

Profiling of lipid species by normal-phase liquid chromatography, nanoelectrospray ionization, and ion trap–orbitrap mass spectrometry

2013

Detailed analysis of lipid species can be challenging due to their structural diversity and wide concentration range in cells, tissues, and biofluids. To address these analytical challenges, we devised a reproducible, sensitive, and integrated lipidomics workflow based on normal-phase liquid chromatography-Fourier transform mass spectrometry (LC-FTMS) and LC-ITMS(2) (ion trap tandem mass spectrometry) for profiling and structural analysis of lipid species. The workflow uses a normal-phase LC system for efficient separation of apolar and polar lipid species combined with sensitive and specific analysis powered by a chip-based nanoelectrospray ion source and a hybrid ion trap-orbitrap mass sp…

Density Functional Study of Spin State in CpM(NO)X2 (M = Mo, Cr; X = Cl, NH2, CH3):  Spectrochemical and Nephelauxetic Effects in Organometallic Comp…

1998

International audience; The relationship between spin state and metal−ligand bonding interactions in CpM(NO)X2 species was investigated using density functional computational techniques. The geometries of CpM(NO)Cl2 (M = Cr, Mo), CpCr(NO)(NH2)X, and CpCr(NO)(CH3)X (X = Cl, CH3) were optimized at the DFT-B3LYP level for both the diamagnetic (S = 0) and paramagnetic (S = 1) electronic configurations. While the geometric parameters of the singlet compounds matched well with structures determined experimentally, the Cr−NO bond lengths in the triplet species exceeded the experimentally observed range by a significant margin, thereby indicating a propensity for nitrosyl-ligand dissociation from t…

Asymmetric Disulfanylbenzamides as Irreversible and Selective Inhibitors of Staphylococcus aureus Sortase A

2020

Abstract Staphylococcus aureus is one of the most frequent causes of nosocomial and community‐acquired infections, with drug‐resistant strains being responsible for tens of thousands of deaths per year. S. aureus sortase A inhibitors are designed to interfere with virulence determinants. We have identified disulfanylbenzamides as a new class of potent inhibitors against sortase A that act by covalent modification of the active‐site cysteine. A broad series of derivatives were synthesized to derive structure‐activity relationships (SAR). In vitro and in silico methods allowed the experimentally observed binding affinities and selectivities to be rationalized. The most active compounds were f…