pyrroloquinoline and Edema

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 E2 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 B4 levels at 4 h, as well as inhibition of prostaglandin E2 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.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonate 5-Lipoxygenase; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Edema; Enzyme Inhibitors; Female; Humans; Isoenzymes; Lipoxygenase Inhibitors; Membrane Proteins; Mice; Monocytes; Pain Measurement; Prostaglandin-Endoperoxide Synthases; Pyrroles; Quinazolines; Quinolines; Sheep