Structure-activity of three phospholipid analogues towards inhibition of phospholipase A2 in macrophages

At concentrations 1-20 mu M in culture medium of rat peritoneal macrophages which were stimulated with ionophore A23187, the phospholipid analogues 1-decyl-2-octyl-glycerophosphocholine and 1-dodecyl-2-octanamido-2-deoxy glycerophosphocholine were found more potent inhibitors than 1-octyl-2-octylthio-2-deoxy glycerophosphocholine to lower the phospholipase A(2) activities. The inhibitory effect was measured by [H-3] eicosatetraenoic acid ([H-3]20:4) release in macrophages and extracellular fluids and synthesis of [H-3] eicosanoids after incubation of macrophages with traces of the molecular species of lecithin 1-octadecanoyl-2-[H-3] eicosatetraenoyl glycerophosphocholine. The three phospholipid analogues developed higher inhibitory effects than mepacrine, dexamethasone or bromophenacyl bromide, at corresponding concentrations in medium. (C) 1997 The Italian Pharmacological Society.