Phospholipase A2 inhibitors in inflammation

Inhibitors of Secretory Phospholipase A2 Group IIA

“…A large number of other structurally distinct sPLA 2 inhibitors have been reported, primarily in the patent literature [106][107][108], but are accompanied by little or usually no biological data . In vitro IC 50 values however are often reported thus making this collection a potentially valuable resource for medicinal chemists concerned with developing computational drug design methods [109,110].…”

Structure—Activity Relationship Studies of 1‐Substituted 3‐Dodecanoylindole‐2‐carboxylic Acids as Inhibitors of Cytosolic Phospholipase A2‐Mediated Arachidonic Acid Release in Intact Platelets.

“…Prostaglandins, leukotrienes, lysophospholipids and PAF are potent mediators of inflammation [1][2][3]. Thus, inhibition of PLA 2 is considered as an interesting target for the design of new anti-inflammatory drugs [4][5][6][7][8].The special attraction of this approach is based on the evidence that, unlike cyclooxygenase inhibitors, inhibitors of PLA 2 not only reduce the formation of prostaglandins, but also suppress the generation of leukotrienes, lysophospholipids, and PAF.Therefore, it can be expected that inhibitors of PLA 2 will possess improved therapeutic activities in comparison to the cyclooxygenase inhibitors therapeutically applied today, such as aspirin, indomethacin, or rofecoxib. One problem associated with the in vitro search for PLA 2 inhibitors is the selection of the appropriate enzyme, since many different PLA 2 s are present in the mammalian organism [9].They can be divided into PLA 2 s utilizing a catalytic histidine and PLA 2 s having a serine at the active site.…”

Structure‐Activity Relationship Studies of 1‐Substituted 3‐Dodecanoylindole‐2‐carboxylic Acids as Inhibitors of Cytosolic Phospholipase A2‐Mediated Arachidonic Acid Release in Intact Platelets

“…Prostaglandins, leukotrienes, lysophospholipids and PAF are potent mediators of inflammation [1][2][3]. Thus, inhibition of PLA 2 is considered as an interesting target for the design of new anti-inflammatory drugs [4][5][6][7][8].The special attraction of this approach is based on the evidence that, unlike cyclooxygenase inhibitors, inhibitors of PLA 2 not only reduce the formation of prostaglandins, but also suppress the generation of leukotrienes, lysophospholipids, and PAF.Therefore, it can be expected that inhibitors of PLA 2 will possess improved therapeutic activities in comparison to the cyclooxygenase inhibitors therapeutically applied today, such as aspirin, indomethacin, or rofecoxib. One problem associated with the in vitro search for PLA 2 inhibitors is the selection of the appropriate enzyme, since many different PLA 2 s are present in the mammalian organism [9].They can be divided into PLA 2 s utilizing a catalytic histidine and PLA 2 s having a serine at the active site.…”