Search results for "endoperoxide"
showing 10 items of 65 documents
Cyclooxygenase-1/2 (COX-1/COX-2) and 5-lipoxygenase (5-LOX) inhibitors of the 6,7-diaryl-2,3-1H-dihydropyrrolizine type
2003
A series of 6,7-diaryl-2,3-1H-dihydropyrrolizines was prepared as COX-1/COX-2 and 5-LOX inhibitors. The inhibition of COX-1 was evaluated using intact bovine platelets as the enzyme source, whereas LPS-stimulated human monocytes served as the enzyme source for inducible COX-2. The determination of arachidonic metabolites was performed by HPLC for COX-1 and RIA for COX-2. The balance between COX-1/COX-2 and 5-LOX inhibition can be shifted by modifying the substitution pattern of the phenyl moiety at the 6- and 7-position of the pyrrolizine nucleus. Structure-activity relationships are discussed.
COX-1/COX-2 inhibitors based on the methanone moiety
2002
This paper focuses on the synthesis and the in vitro testing of dual COX-1/COX-2 inhibitors. Starting from structures of non-steroidal anti-inflammatory drugs (NSAIDs) the diaryl methanone element was chosen as a lead. Modifications were carried out on this scaffold to obtain potent inhibitors of the COX enzymes. The N-(2-aroylphenyl)sulphonamides and -amides were studied in detail, and to consolidate the data evaluated the corresponding 3- and 4-regioisomers were also investigated. The potency and the enzyme selectivity were varied by structural modifications of the lead.
Spectrofluorimetric Quantification of Malondialdehyde for Evaluation of Cyclooxygenase-1/Thromboxane Synthase Inhibition
1999
The in vitro assay developed by Hartmann and Ledergerber (1995) utilizing the spectrofluorimetric quantification of malondialdehyde after reaction with thiobarbituric acid was modified and used for further investigations. The human whole blood was replaced by a platelet suspension of pig blood, and calcium ionophore A23187 was used instead of collagen for inducing the arachidonic acid cascade. The modified assay represents a simple, time and cost saving method for the evaluation of cyclooxygenase-1/thromboxane synthase inhibition. The reproducibility and comparability of results is given. Additional experiments allow classification of selective phospholipase A2, cyclooxygenase-1, and thromb…
Griffonianone D, an isoflavone with anti-inflammatory activity from the root bark of Millettia griffoniana.
2003
A new isoflavone, griffonianone D (1), and the previously known compounds durmillone and odorantin were isolated from a chloroform extract of the root bark of Millettia griffoniana. The structure of 1 was established as (7E)-(6",7"-dihydroxy-3",7"-dimethyloct-2"-enyl)oxy-4'-methoxyisoflavone on the basis of its spectral data. The chloroform extract of the root bark of M. griffoniana and compound 1 showed anti-inflammatory effects in different experimental models of inflammation.
In-vitro test system for the evaluation of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) inhibitors based on a single HPLC run with UV detect…
2001
Objective and Design: The aim of this study was to develop a new, whole-cell test system which is easy to handle and requires a standard equipment for the parallel screening of COX-1 and COX-2 inhibitors.¶Materials: Bovine aortic endothelial cells (BAECs).¶Treatment and methods: Unstimulated bovine aortic coronary endothelial cells (BAECs) were used as a source of COX-1 and BAECs pretreated with ASA (100 μM) and activated with phorbol myristate acetate (PMA) were used as a source of COX-2. The time- and concentration-dependent induction of COX-2 expression in the BAECs was evaluated by a kinetic profile (HPLC analysis) and detected by Western-Blot analysis using polyclonal antibodies agains…
Dual inhibition of cyclooxygenase-1 and 5-lipoxygenase by aerial part of Bupleurum fruticescens methanol extract
2003
The effect of the methanol extract from aerial parts of Bupleurum fruticescens on the release of eicosanoids and hydrolytic enzymes was determined on in vitro cell systems. The extract had a significant effect on 5-lipoxygenase (5-LOX) activity, inhibiting both LTB4 and 5(S)-HETE production with IC50 values of 112 microg/ml and 95 microg/ml, respectively. At concentrations of 200 microg/ml, the extract also inhibited cyclooxygenase-1 (90%) and elastase activities (54%). The 12-LOX activity in intact platelets was not affected; a fact, which suggests that phospholipase A2 (PLA2) activity, is not modified by the extract.
Avarol restores the altered prostaglandin and leukotriene metabolism in monocytes infected with human immunodeficiency virus type 1
1991
Abstract Infection of monocytes with human immunodeficiency virus type 1 (HIV-1) (strain Ada-M) caused increased levels of leukotriene B 4 (LTB 4 ) and prostaglandin E 2 (PGE 2 ) in vitro. These two products result from the activities of the two enzymes cyclooxygenase and 5-lipoxygenase. The addition of the sesquiterpenoid hydroquinone Avarol, an HIV inhibitor, strongly reduced the levels of LTB 4 and PGE 2 via inhibition of both cyclooxygenase and lipoxygenase in monocytes. The 50% inhibition concentrations (IC 50 ) for the enzymes were determined to be 2.26 μM (cyclooxygenase) and 1.97 μM (lipoxygenase). A 50% reduction of the extent of PGE 2 and LTB 4 production in HIV-infected monocytes…
Pharmacogenomics: a tool to prevent and cure coronary heart disease.
2007
Inflammation and genetics play an important role in the pathogenesis of coronary heart disease (CHD). This is supported by epidemiological studies which have thoroughly investigated the association between CHD and gene polymorphisms of the inflammatory molecules. Moreover, efforts to find elective therapy have not been rewarding and, despite the increasing appreciation of the role of genetics in CHD and myocardial infarction (MI) pathogenesis, pharmacogenomic approaches to uncover drug target have not been extensively explored. A critical search of published literature has suggested few inflammatory genes directly involved in the risk to develop CHD and MI. The selected genes are, the pro- …
Induction of apoptosis and inhibition of cell growth in human hepatocellular carcinoma cells by COX-2 inhibitors
2005
The aim of the present study was to examine the effects of nonselective (indomethacin) and selective cyclooxygenase-2 (COX-2) inhibitors (NS-398, nimesulide, and CAY10404) on cell growth, cell cycle distribution, and apoptosis in three human hepatocellular carcinoma cell lines (HepG2, HuH-6, and HA22T/VGH) with different characteristics of differentiation and biological behavior. The four COX inhibitors showed a dose-dependent growth-inhibitory effect in all the cell lines. No substantial arrests in the progression of the cells through the cell cycle were observed after treatment of HuH-6 or HA22T/VGH for 48 h with the various inhibitors. On the other hand, there were significant increases …
Synthesis and anti-inflammatory activity of chalcone derivatives
1998
Chalcones and their derivatives were synthesized and evaluated for their anti-inflammatory activity. In vitro, chalcones 2, 4, 8, 10 and 13 inhibited degranulation and 5-lipoxygenase in human neutrophils, whereas 11 behaved as scavenger of superoxide. Only four compounds (4-7) inhibited cyclo-oxygenase-2 activity. The majority of these samples showed anti-inflammatory effects in the mouse air pouch model.