Τίτλος:
Differential inhibition of group IVA and group VIA phospholipases A 2 by 2-oxoamides
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Inhibitors of the Group IVA phospholipase A2 (GIVA CPLA 2) and GVIA iPLA2 are useful tools for defining the roles of these enzymes in cellular signaling and inflammation. We have developed inhibitors of GVIA iPLA2 building upon the 2-oxoamide backbone that are uncharged, containing ester groups. Although the most potent inhibitors of GVIA iPLA2 also inhibited GIVA cPLA2, there were three 2-oxoamide compounds that selectively and weakly inhibited GVIA iPLA 2. We further show that several potent 2-oxoamide inhibitors of GIVA cPLA2 containing free carboxylic groups (Kokotos et al. J. Med. Chem. 2002, 45, 2891-2893) do not inhibit GVIA iPLA2 and are, therefore, selective GIVA cPLA2 inhibitors. © 2006 American Chemical Society.
Συγγραφείς:
Stephens, D.
Barbayianni, E.
Constantinou-Kokotou, V.
Peristeraki, A.
Six, D.A.
Cooper, J.
Harkewicz, R.
Deems, R.A.
Dennis, E.A.
Kokotos, G.
Περιοδικό:
Journal of Medicinal Chemistry
Λέξεις-κλειδιά:
2 oxoamide inhibitor; amide; carboxylic acid derivative; phospholipase A2; phospholipase A2 group IVA; phospholipase A2 group VIA; phospholipase A2 inhibitor; unclassified drug, animal cell; animal tissue; article; controlled study; drug potency; enzyme inhibition; inflammation; mouse; nonhuman; signal transduction; structure activity relation, Animals; Cell Line; Dinoprostone; Enzyme Inhibitors; Mice; Molecular Structure; Phospholipases A; Pyridines; Structure-Activity Relationship
