Abstract
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 is needed.
MeSH terms
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Arachidonate 5-Lipoxygenase / drug effects*
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Blood Platelets / drug effects
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Blood Platelets / enzymology
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Cyclooxygenase 1
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Cyclooxygenase Inhibitors / chemical synthesis*
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Cyclooxygenase Inhibitors / pharmacology*
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Female
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Humans
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Isoenzymes / drug effects*
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Lipoxygenase Inhibitors / chemical synthesis*
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Lipoxygenase Inhibitors / pharmacology*
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Male
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Membrane Proteins
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Neutrophils / drug effects
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Neutrophils / enzymology
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Prostaglandin-Endoperoxide Synthases / drug effects*
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Pyrroles / chemical synthesis*
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Pyrroles / pharmacology*
Substances
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Cyclooxygenase Inhibitors
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Isoenzymes
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Lipoxygenase Inhibitors
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Membrane Proteins
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Pyrroles
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Arachidonate 5-Lipoxygenase
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Cyclooxygenase 1
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PTGS1 protein, human
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Prostaglandin-Endoperoxide Synthases