Structure-activity relationships of natural and non-natural amino acid-based amide and 2-oxoamide inhibitors of human phospholipase A(2) enzymes.
A variety of 2-oxoamides and related amides based on natural and non-natural amino acids were synthesized. Their activity on two human intracellular phospholipases (GIVA cPLA(2) and GVIA iPLA(2)) and one human secretory phospholipase (GV sPLA(2)) was evaluated. We show that an amide based on (R)-gamma-norleucine is a highly selective inhibitor of GV sPLA(2).
Antonopoulou
Georgia
G
Laboratory of Organic Chemistry, Department of Chemistry, University of Athens, Panepistimiopolis, Athens 15771, Greece.
Barbayianni
Efrosini
E
Magrioti
Victoria
V
Cotton
Naomi
N
Stephens
Daren
D
Constantinou-Kokotou
Violetta
V
Dennis
Edward A
EA
Kokotos
George
G
D000577:Amides / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000577:Amides; D000596:Amino Acids; D004791:Enzyme Inhibitors; D064801:Phospholipase A2 Inhibitors; D011725:Pyridines; C034960:oxoamide; D054467:Phospholipases A2