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A pyrroloquinazoline derivative with anti-inflammatory and analgesic activity by dual inhibition of cyclo-oxygenase-2 and 5-lipoxygenase
- Source :
- ResearcherID
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Abstract
- In a previous study, we reported a new pyrroloquinazoline derivative, 3-(4′-acetoxy-3′,5′-dimethoxy)benzylidene-1,2-dihydropyrrolo[2,1- b ]quinazoline-9-one (PQ), which inhibited human purified 5-lipoxygenase activity and prostaglandin E 2 release in lipopolysaccharide-stimulated RAW 264.7 cells. In the present work, we show that PQ inhibits cyclo-oxygenase-2 activity in intact cell assays (human monocytes) and purified enzyme preparations (ovine isoenzymes) without affecting cyclo-oxygenase-1 activity. This behaviour was confirmed in vivo by using the zymosan-injected mouse air pouch model, where PQ caused a marked reduction in cell migration and leukotriene B 4 levels at 4 h, as well as inhibition of prostaglandin E 2 levels without affecting cyclo-oxygenase-2 expression at 24 h after zymosan stimulation. In addition, oral administration of this compound significantly reduced carrageenan-induced mouse paw oedema and phenyl- p -benzoquinone-induced writhings in mice. These results indicate that oral PQ exerts analgesic and anti-inflammatory effects, which are related to dual inhibition of cyclo-oxygenase-2 and 5-lipoxygenase activities.
- Subjects :
- medicine.medical_treatment
Pharmacology
Monocytes
Mice
chemistry.chemical_compound
In vivo
medicine
Animals
Edema
Humans
Cyclooxygenase Inhibitors
Pyrroles
Lipoxygenase Inhibitors
Enzyme Inhibitors
Prostaglandin E2
Pain Measurement
Analgesics
Arachidonate 5-Lipoxygenase
Sheep
Cyclooxygenase 2 Inhibitors
Dose-Response Relationship, Drug
biology
Chemistry
Anti-Inflammatory Agents, Non-Steroidal
Zymosan
Membrane Proteins
Biological activity
Isoenzymes
Biochemistry
Mechanism of action
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases
Enzyme inhibitor
Arachidonate 5-lipoxygenase
Quinazolines
Quinolines
biology.protein
Female
medicine.symptom
Prostaglandin E
medicine.drug
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- ResearcherID
- Accession number :
- edsair.doi.dedup.....04e636978ca0d02eb7fd912a0395d20d