Novel 2-oxoamide inhibitors of human group IVA phospholipase A(2).
A novel class of potent human cytosolic phospholipase A(2) (GIVA PLA(2)) inhibitors was developed. These inhibitors were designed to contain the 2-oxoamide functionality and a free carboxyl group. Among the compounds tested, a long-chain 2-oxoamide containing L-gamma-norleucine was the most potent inhibitor, causing a 50% decrease in GIVA PLA(2) activity at 0.009 mole fraction.
Kokotos
George
G
Laboratory of Organic Chemistry, Department of Chemistry, University of Athens, Panepistimiopolis, Athens 15771, Greece. gkokotos@cc.uoa.gr
Kotsovolou
Stavroula
S
Six
David A
DA
Constantinou-Kokotou
Violetta
V
Beltzner
Christopher C
CC
Dennis
Edward A
EA
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D054513:Group IV Phospholipases A2; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009646:Norleucine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000577:Amides; D004791:Enzyme Inhibitors; D009646:Norleucine; D010741:Phospholipases A; D054513:Group IV Phospholipases A2; C516389:PLA2G4A protein, human