Search results for "Pyrroles"
showing 10 items of 121 documents
The relaxant effects of cromakalim (BRL 34915) on human isolated airway smooth muscle
1992
Cromakalim (BRL 34915) is a potassium channel opener with therapeutic potential as a bronchodilator in asthma. Cromakalim (0.1–30 μmol/l) inhibited the spontaneous tone of human isolated bronchi n a concentration-related manner being nearly as effective as isoprenaline or theophylline. The order of relaxant potencies (expressed as -log10 IC50 mol/l; mean ±SEM) was isoprenaline (7.29 ± 0.27; n = 8) > cromakalim (5.89 ± 0.12; n = 7) > theophylline (4.07 ±0.13; n = 10). In human bronchi where tone had been raised by addition of histamine (0.1 mmol/l), acetylcholine (0.1 mmol/l) or leukotriene D4 (LTD4, 0.1 μmol/l), the relaxant effect of cromakalim was substantially reduced. Cromakalim suppres…
Effects of SCA40 on human isolated bronchus and human polymorphonuclear leukocytes: comparison with rolipram, SKF94120 and levcromakalim
1996
1. SCA40 (0.1 nM-0.1 mM) produced concentration-dependent suppression of the spontaneous tone of human isolated bronchus (-log EC50 = 6.85 +/- 0.09; n = 10) and reached a maximal relaxation similar to that of theophylline (3 mM). The potency (-log EC50 values) of SCA40 compared to other relaxants was rolipram (7.44 +/- 0.12; n = 9) > SCA40 > or = levcromakalim (6.49 +/- 0.04; n = 6) > SKF94120 (5.87 +/- 0.10; n = 9). 2. When tested against the activity of the isoenzymes of cyclic nucleotide phosphodiesterase (PDE) isolated from human bronchus, SCA40 proved highly potent against PDE III (-log IC50 = 6.47 +/- 0.16; n = 4). It was markedly less potent against PDE IV (4.82 +/- 0.18; n = 4) and …
Mechanical and electrophysiological effects of cromakalim on the human urinary bladder.
1994
The effects of cromakalim on spontaneous and induced mechanical activity of human detrusor muscle were investigated in vitro. Cromakalim produces a concentration-related decrease of spontaneous as well as carbachol- and K(+)-evoked contractions. This is the first study to utilize the patch clamp technique to elucidate the mechanism of action of cromakalim on human detrusor cells. Cromakalim hyperpolarizes the detrusor cells by increasing the net outward current which is most likely carried by potassium ions. In the human urinary bladder, this effect is mediated by a glibenclamide-sensitive potassium channel, as glibenclamide is able to diminish the relaxant effect of cromakalim and to preve…
The pyrrole moiety as a template for COX-1/COX-2 inhibitors
2000
Aroyl- and thiophene-substituted pyrrole derivatives have been synthesized as a new class of COX-1/COX-2 inhibitors. The inhibition of COX-1 was evaluated in a biological system using bovine PMNLs as the enzyme source, whereas LPS-stimulated human monocytes served as the enzyme source for inducible COX-2. The determination of the concentration of arachidonic acid metabolites was performed by HPLC for COX-1 and RIA for COX-2. Variation of the substitution pattern led to a series of active compounds which showed inhibition for COX-1 and COX-2. Structural requirements for the development of COX-1/COX-2 inhibitors are discussed.
Licofelone, a novel 5-LOX/COX-inhibitor, attenuates leukocyte rolling and adhesion on endothelium under flow
2005
The main mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs) is the inhibition of cycloxygenases COX-1 and COX-2. During recent years, combined 5-LOX/COX-inhibition, interfering with the biosynthesis of both prostaglandins and leukotrienes (LTs), has emerged as a possibility to avoid side effects related to COX-inhibition. The aim of the present study was to investigate if there is a contribution of mechanisms other than the reduction of inflammatory prostaglandins and leukotrienes to the anti-inflammatory effect of the LOX/COX inhibitor licofelone. In a flow chamber assay, licofelone (10-30 microM) dose-dependently decreased both the rolling and adhesion of leukocytes on …
Self-Assembly-Directed Organization of a Fullerene–Bisporphyrin into Supramolecular Giant Donut Structures for Excited-State Charge Stabilization
2021
Functional materials composed of spontaneously self-assembled electron donor and acceptor entities capable of generating long-lived charge-separated states upon photoillumination are in great demand as they are key in building the next generation of light energy harvesting devices. However, creating such well-defined architectures is challenging due to the intricate molecular design, multistep synthesis, and issues associated in demonstrating long-lived electron transfer. In this study, we have accomplished these tasks and report the synthesis of a new fullerene–bis-Zn-porphyrin e-bisadduct by tether-directed functionalization of C60 via a multistep synthetic protocol. Supramolecular oligom…
Synthesis and antiproliferative activity of thiazolyl-bis-pyrrolo[2,3-b]pyridines and indolyl-thiazolyl-pyrrolo[2,3-c]pyridines, nortopsentin analogu…
2015
Two new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and indole units were both substituted by 7-azaindole moieties or one indole unit was replaced by a 6-azaindole portion, were efficiently synthesized. Compounds belonging to both series inhibited the growth of HCT-116 colorectal cancer cells at low micromolar concentrations, whereas they did not affect the viability of normal-like intestinal cells. A compound of the former series induced apoptosis, evident as externalization of plasma membrane phosphatidylserine (PS), and changes of mitochondrial trans-membrane potential, while blocking the cell cycle in G2/M phase. In contr…
High osmolarity glycerol (HOG) signalling in Magnaporthe oryzae: Identification of MoYPD1 and its role in osmoregulation, fungicide action, and patho…
2015
AbstractThis study comprises a first functional analysis of an YPD1-homologue in filamentous phytopathogenic fungi and its role in the HOG signalling pathway. We generated a gene deletion mutant of the gene MoYPD1 in Magnaporthe oryzae and characterized the resulting mutant strain. We have shown that MoYpd1p is a component of the phosphorelay system acting in the HOG pathway due to its Y2H protein interaction with the HKs MoHik1p and MoSln1p as well as with the response regulator MoSsk1p. Fungicidal activity of fludioxonil was reported to be based on the inhibition of MoHik1p resulting in hyperactivation of the HOG signalling pathway and lethality. Western analysis proved that both, osmotic…
Rapid adaptation of signaling networks in the fungal pathogen Magnaporthe oryzae
2019
Abstract Background One fundamental question in biology is how the evolution of eukaryotic signaling networks has taken place. “Loss of function” (lof) mutants from components of the high osmolarity glycerol (HOG) signaling pathway in the filamentous fungus Magnaporthe oryzae are viable, but impaired in osmoregulation. Results After long-term cultivation upon high osmolarity, stable individuals with reestablished osmoregulation capacity arise independently from each of the mutants with inactivated HOG pathway. This phenomenon is extremely reproducible and occurs only in osmosensitive mutants related to the HOG pathway – not in other osmosensitive Magnaporthe mutants. The major compatible so…
Profile and molecular modeling of 3-(indole-3-yl)-4-(3,4,5-trimethoxyphenyl)-1 H-pyrrole-2,5-dione (1) as a highly selective VEGF-R2/3 inhibitor.
2006
We report on selectivity profiling of 1 in a panel of 20 protein kinases and molecular modeling indicating 1 to be highly active and selective for VEGF-R2/3. Sequence alignment analysis and detailed insights into the ATP binding pockets of targeted protein kinases from the panel result in a unique structural architecture of VEGF-R2 mainly caused by the hydrophobic pocket I, determining the molecular basis for activity and selectivity of 1.