Summary:
Phospholipases A2 (PLA2) are enzymes that hydrolyze the sn-2 ester bond of
phospholipids releasing free fatty acids and lysophospholipids. Among them,
arachidonic acid can be converted into a variety of eicosanoids by metabolic
enzymes, while lysophosphatidylcholine (LPC), the most abundant
lysophospholipid in plasma and tissues, can be converted into lysophosphatidic
acid (LPA) by a secreted enzyme that exhibits lysophospholipase D activity,
known as autotaxin (ATX). Both enzymes are involved in inflammatory conditions
and, as a consequence, constitute attractive targets for the development of
novel agents for the treatment of inflammatory diseases.
Due to the fact that molecules which bear the 2-oxoamide functional group and
long aliphatic chains exhibit inhibitory activity against cytosolic GIVA cPLA2,
2-oxoamides with reduced lipophilicity were designed and synthesized.
Taking into consideration that in recent years hydroxamic acids have attracted
considerable attention due to their pharmacological properties, hydroxamic
acids and derivatives thereof were designed and synthesized, so as to evaluate
their inhibitory activity against ATX.
Keywords:
Phospholipase A2, Autotaxin, Oxoamide, Hydroxamic acid, Inhibitor
