Search results for "Lipoxygenase Inhibitors"
showing 10 items of 26 documents
Modulation of COX, LOX and NFκB activities by Xanthium spinosum L. root extract and ziniolide.
2012
Xanthium spinosum L. (Asteraceae) is a medicinal weed distributed worldwide. Many of its diverse ethnopharmacological uses - namely diarrhoea, inflammation, liver disorders, snake bite and fever - are linked - at least in part - to an uncontrolled release of arachidonic acid metabolites. The crude extract of X. spinosum roots from Jordanian origin dose-dependently inhibited the 5-LOX (IC50 is approximately equal to 10 μg/mL), COX-1(IC50 is approximately equal to 50 μg/mL), and 12-LOX (IC50 is approximately equal to 170 μg/mL) enzymatic pathways in intact pro-inflammatory cells. A direct activity at the level of PLA2 is not probable, but the extract induced the synthesis of the anti-inflamma…
Investigations concerning the COX/5-LOX inhibiting and hydroxyl radical scavenging potencies of novel 4,5-diaryl isoselenazoles
2007
The aim of this study was to investigate 4,5-diaryl isoselenazoles as multiple target non-steroidal anti-inflammatory drugs (MTNSAIDs) which can intervene into the inflammatory processes via different mechanisms of action creating a new class of compounds. Here we describe the synthesis of COX/LOX inhibitors which additionally reduce the level of reactive oxygen species, such as hydroxyl radicals which are well known for supporting inflammation processes in Parkinson's disease, Alzheimer's disease and rheumatoid arthritis.
Synthesis and Evaluation of a Novel Series of Pyrrolizine Derivatives as Dual Cyclooxygenase-1 and 5-Lipoxygenase Inhibitors
1997
The aim of our study was to investigate structure activity relationship following the replacement of the 6-phenyl substituent at the 6,7-diaryl-2,3-dihydropyrrolizine template by various heteroaromatic residues. In this context we developed a new, efficient, and highly sensitive test method for the screening of dual cyclooxygenase-1 (COX-1) and 5-lipoxygenase (5-LOX) inhibitors. We used human platelets as a source of COX-1 and human PMNLs as a source of 5-LOX. Both cell types were isolated from the same volume of blood. PGE2 and LTB4 respectively were determined by highly selective and sensitive ELISA kits, using monoclonal antibodies. For a single determination at most 0.5 mL whole blood i…
Non-steroidal Anti-inflammatory Agents, Part 19:E-2-Pyrrolizin-5-yl Acrylic Acids as Potent Dual or Selective Inhibitors of Bovine Cyclooxygenase and…
1995
The pyrrolizinyl substituted acrylic acid derivatives represent another class of dual and selective inhibitors of cyclooxygenase and 5-lipoxygenase. By modifying their substitution pattern at the phenyl moiety of C-6 the balance between the activity against cyclooxygenase and against 5-lipoxygenase can be shifted. Structure-activity relationships are discussed. Compound 6k is the most potent and well-balanced dual inhibitor of both enzymes, while the highest selectivity of lipoxygenase inhibition was found for 6j. The activity and selectivity of compounds with an additional sulfur moiety depend on the oxidation status of this atom, giving an indication of the discussed coupling between pero…
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.
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…
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…
Phenylsulphonyl urenyl chalcone derivatives as dual inhibitors of cyclo-oxygenase-2 and 5-lipoxygenase
2005
Two series of phenylsulphonyl urenyl chalcone derivatives (UCH) with various patterns of substitution were tested for their effects on nitric oxide (NO) and prostaglandin E2 (PGE2) overproduction in RAW 264.7 macrophages. None of the tested compounds reduced NO production more than 50% at 10 microM but most of them inhibited the generation of PGE2 with IC50 values under the micromolar range. Me-UCH 1, Me-UCH 5, Me-UCH 9, Cl-UCH 1, and Cl-UCH 9 were selected to evaluate their influence on human leukocyte functions and eicosanoids generation. These derivatives selectively inhibited cyclo-oxygenase-2 (COX-2) activity in human monocytes being Me-UCH 5 the most potent (IC50 0.06 microM). Selecte…
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.
Evaluation of the anti-inflammatory and analgesic activity of Me-UCH9, a dual cyclooxygenase-2/5-lipoxygenase inhibitor
2007
Abstract Recently, we reported the dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO) activity by some phenylsulphonyl urenyl chalcone derivatives. 2,4-dichloro-4′ N [ N ′(4″methylphenylsulphonyl)urenyl] chalcone (Me-UCH9), was selected in the present study to determine its potential anti-inflammatory and analgesic effect after oral administration in several animal models related to the activation of COX-2 and 5-LO pathways. In the zymosan stimulated mouse air pouch model, Me-UCH9, reduced in a dose-dependent manner leukotriene B 4 (LTB 4 ) levels in pouch exudates obtained at 4 h, as well as prostaglandin E 2 (PGE 2 ) generated through COX-2 activation at 24 h. Tumor nec…