Search results for "Pyrroles"

Mechanisms underlying recoupling of eNOS by HMG-CoA reductase inhibition in a rat model of streptozotocin-induced diabetes mellitus

2007

Abstract Objective HMG-CoA reductase inhibitors have been shown to upregulate GTP cyclohydrolase I (GTPCH-I), the key enzyme for tetrahydrobiopterin de novo synthesis and to normalize tetrahydrobiopterin levels in hyperglycemic endothelial cells. We sought to determine whether in vivo treatment with the HMG-CoA reductase inhibitor atorvastatin is able to upregulate the GTPCH-I, to recouple eNOS and to normalize endothelial dysfunction in an experimental model of diabetes mellitus. Methods and results In male Wistar rats, diabetes was induced by streptozotocin (STZ, 60mg/kg). In STZ rats, atorvastatin feeding (20mg/kg/d, 7 weeks), normalized vascular dysfunction as analyzed by isometric tens…

Efficacy and safety of ezetimibe added to atorvastatin versus atorvastatin uptitration or switching to rosuvastatin in patients with primary hypercho…

2013

Hypercholesterolemic patients (n = 1,547) at high atherosclerotic cardiovascular disease risk with low-density lipoprotein cholesterol (LDL-C) levels ≥100 and ≤160 mg/dl while treated with atorvastatin 10 mg/day entered a multicenter, randomized, double-blind, active-controlled, clinical trial using two 6-week study periods. Period I compared the efficacy/safety of (1) adding ezetimibe 10 mg (ezetimibe) to stable atorvastatin 10 mg, (2) doubling atorvastatin to 20 mg, or (3) switching to rosuvastatin 10 mg. Subjects in the latter 2 groups who persisted with elevated LDL-C levels (≥100 and ≤160 mg/dl) after period I, entered period II; subjects on atorvastatin 20 mg had ezetimibe added to th…

Decreased plasma soluble RAGE in patients with hypercholesterolemia: Effects of statins

2007

The receptor for advanced glycation endproducts (RAGE) is overexpressed at sites of vascular pathology. A soluble RAGE isoform (sRAGE) neutralizes the ligand-mediated damage by acting as a decoy. We hypothesized that in hypercholesterolemia up-regulation of the ligand-RAGE axis may bridge impairment of nitric oxide biosynthesis with oxidative stress. We measured in 60 hypercholesterolemic patients and 20 controls plasma total sRAGE levels, urinary 8-iso-prostaglandin (PG) F(2alpha) excretion, and plasma levels of asymmetric dimethylarginine (ADMA). The effects of two structurally different statins (pravastatin and atorvastatin) on these parameters were analyzed in 20 hypercholesterolemic su…

Flow-mediated dilation in patients with coronary artery disease is enhanced by high dose atorvastatin compared to combined low dose atorvastatin and …

2009

Abstract Background Effects independent from cholesterol reduction on vascular function are considered to importantly contribute to the beneficial effects of statin therapy in cardiovascular disease. We aimed to evaluate the effect of high versus low dose atorvastatin on endothelial dysfunction in patients with coronary artery disease (CAD) in a setting of comparable cholesterol reduction. Methods and results Fifty-eight patients with CAD were randomly assigned to double-blind treatment for 8 weeks with atorvastatin 80mg per day (A80) or atorvastatin 10mg+ezetimibe 10mg per day (A10E10), respectively. Flow-mediated vasodilation (FMD) of the brachial artery, nitroglycerin-mediated endotheliu…

Dispacamide E and other bioactive bromopyrrole alkaloids from two Indonesian marine sponges of the genus Stylissa.

2014

Chemical investigation of methanolic extracts of the two Indonesian marine sponges Stylissa massa and Stylissa flabelliformis yielded 25 bromopyrrole alkaloids including 2 new metabolites. The structures of all isolated compounds were unambiguously elucidated based on extensive 1D and 2D NMR, LR-MS and HR-MS analyses. All isolated compounds were assayed for their antiproliferative and protein kinase inhibitory activities. Several of the tested compounds revealed selective activity(ies) which suggested preliminary SARs of the isolated bromopyrrole alkaloids.

In vitro anti-Gram-positive and anti-staphylococcal biofilm activity of newly halogenated pyrroles related to Pyrrolomycins

2007

3,4,5,3’,5’-pentabromo-2-(2’-hydroxybenzoyl) pyrrole: a potential lead compound as anti Gram-positive and anti biofilm agent

2005

The activity against Gram-positive bacteria of 3,4,5,3 ,5 -pentabromo-2-(2 -hydroxybenzoyl)pyrrole I, a synthetic anti-bacterial compound related to pyrrolomycins, was tested in vitro using seven reference bacterial strains and Staphylococcus epidermidis and Staphylococcus aureus preformed biofilms. Compound I was active against all strains tested, with minimum inhibitory concentration (MIC) values ranging from 0.002 to 0.097 mg/l and minimum bactericidal concentrations (MBCs) from 0.37 to 12.5 mg/l. Compound I was also active at low concentrations against preformed S. epidermidis and S. aureus biofilms.

Confinement inside a Crystalline Sponge Induces Pyrrole To Form N−H⋅⋅⋅π Bonded Tetramers

2021

Based on the DFT‐level calculated molecular volume (V mol ) of pyrrole and its liquid density, pyrrole manifests the highest liquid density coefficient LD c (defined as [V mol • density • 0.6023]/FW) value of 0.7. Normal liquids have LD c < 0.63. This very high LD c is due to the strong N‐H … π interactions in solution and hence pyrrole can be considered to be a pseudo‐crystalline liquid. When trapped inside the confined space of the crystalline sponge a reorientation of the N‐H … π interaction is observed leading to specific cyclic N‐H … π tetramers and N‐H … π dimers, verified by single crystal X‐ray crystallographic and computational methods. These tetramers are of the same size as four …

Design, Synthesis, and Biological Evaluation of 3,4-Diarylmaleimides as Angiogenesis Inhibitors

2006

The new analogue 2 of combretastatin A-4 was discovered to be an inhibitor of tubulin polymerization with an IC50 of 7.6 microM and reduced angiogenesis in the in vivo chick embryo model. Interestingly, in a series of 2,3-diarylmaleimides closely related to this lead, no other compound was found to be active in the tubulin polymerization assay. However, by screening in the in vivo chick embryo assay 10 was identified as a potent angiogenesis inhibitor indicating an alternative target. Indeed, molecular modeling studies suggest a reasonable binding mode of 10 at the ATP-binding site of the model kinase CDK2. Motivated by these results, analogues of 10 were screened for inhibitory activity in…

Stepwise sequential redox potential modulation possible on a single platform.

2011

Step by step: The cluster [3,3'-Co(1,2-C(2)B(9)H(11))(2)](-) is an excellent platform for making a stepwise tunable redox potential system by dehydroiodination. With the addition of up to eight iodine substituents (purple; see picture), there is a fall in the E(1/2)(Co(III)/Co(II)) value from -1.80 V to -0.68 V (vs. Fc(+)/Fc; Fc = ferrocene). A practical application of this tunability has been observed in the growth of polypyrrole.