Structure-activity relationships of natural and non-natural amino acid-based amide and 2-oxoamide inhibitors of human phospholipase A(2) enzymes

Bioorg Med Chem. 2008 Dec 15;16(24):10257-69. doi: 10.1016/j.bmc.2008.10.046. Epub 2008 Nov 1.

Abstract

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).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry
  • Amino Acids / chemistry*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Structure
  • Phospholipase A2 Inhibitors*
  • Phospholipases A2 / pharmacology
  • Pyridines / chemistry*
  • Structure-Activity Relationship

Substances

  • Amides
  • Amino Acids
  • Enzyme Inhibitors
  • Phospholipase A2 Inhibitors
  • Pyridines
  • oxoamide
  • Phospholipases A2