341973-06-6

The group IVA phospholipase A₂ (PLA₂), known as calcium-dependent cytosolic PLA₂ (cPLA₂), selectively releases arachidonic acid (AA) from membrane phospholipids, playing a central role in initiating the synthesis of prostaglandins (PGs) and leukotrienes (LTs). Pyrrophenone inhibits cPLA₂α with an IC₅₀ of 4.2 nM in enzyme assays and potently blocks the release of AA and the production of PGE₂ and LTC₄ in cells (IC₅₀ = 24, 25, and 14 nM, respectively). Its action is reversible and selective, as pyrrophenone inhibits the secretory type IB and IIA PLA₂s with more than a hundred-fold less potency. Pyrrophenone has also been shown to inhibit calcium ionophore (A23187)-stimulated AA release from monocytic cells, interleukin-1-induced PGE₂ synthesis in mesangial cells, and the production of PGE₂, LTs, and platelet-activating factor by human neutrophils, always with maximal inhibition at concentrations below 1 μM.