3-(Octadecanoylaminomethyl)indole-2-carboxylic acid derivatives and 1-methyl-3-octadecanoylindole-2-carboxylic acid as inhibitors of cytosolic phospholipase A2.
3-(1-Acylaminooctadecyl)indole-2-carboxylic acids and 3-(1-acylaminooctadecyl)-1-methylindole-2-carboxylic acids were designed and synthesized as inhibitors of cytosolic phospholipase A2. Enzyme inhibition was assayed by evaluation of calcium ionophore A23187-induced arachidonic acid release from bovine platelets. While compounds with 1-octadecanoylaminooctadecyl groups in position 3 of the indole were inactive inhibition data for 3-[1-(3-phenylpropionylamino)octadecyl]indole-2-carboxylic acids could not be evaluated because of lysis of the platelets. However 3-(octadecanoylaminomethyl)indole-2-carboxylic acid derivatives and 1-methyl-3-octadecanoylindole-2-carboxylic acid proved to be inhibitors of cytosolic phospholipase A2. The most active inhibitor was the latter compound with an IC50 of 8 microM.
Lehr
M
M
Institute für Pharmazie und Lebensmittelchemie, Ludwig-Maximilians-Universität, München, Germany.
D000818:Animals; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D002417:Cattle; D003600:Cytosol / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2
D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D010741:Phospholipases A; D054467:Phospholipases A2