Σύνθεση και μελέτη αναστολέων λιπολυτικών ενζύμων

Abstract

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-oxoamideswith 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 there of were designed and synthesized, so as to evaluate their inhibitory activity against ATX.