Synthesis and evaluation of substrate-mimicking cytosolic phospholipase A2 inhibitors--reducing the lipophilicity of the arachidonyl chain isostere

Bioorg Med Chem Lett. 2004 Jul 16;14(14):3645-9. doi: 10.1016/j.bmcl.2004.05.024.

Abstract

The high lipophilicity of a series of cytosolic phospholipase A(2) inhibitors has been reduced by the modification of a decyloxyphenyl chain designed to mimic the arachidonyl group of the natural substrate. These changes have resulted in an improvement in the whole cell potency of the inhibitors.

MeSH terms

  • Arachidonic Acid / chemistry
  • Arachidonic Acid / metabolism*
  • Cytosol / chemistry*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology*
  • HL-60 Cells
  • Humans
  • Inhibitory Concentration 50
  • Molecular Mimicry
  • Phospholipases A / antagonists & inhibitors*
  • Phospholipases A / metabolism
  • Phospholipases A2
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Arachidonic Acid
  • Phospholipases A
  • Phospholipases A2