3D-QSAR pharmacophore modeling and in silico screening of phospholipase A2α inhibitors

Abstract

Cytosolic phospholipase A2α have emerged as an attractive target for the development of analgesic and anti-inflammatory drugs. 3D-QSAR pharmacophore model was developed, based on previously reported 28 indole-5-carboxylic acids, and used to understand the structural factors affecting the inhibitory potency of these derivatives. Hydrogen bond acceptor, negative charge, and aromatic effects contribute to the inhibitory activity. The model was employed as a 3D search query to screen SPECS database to select new scaffolds. Finally, docking studies lead to the identification of fourteen potential phospholipase A2α inhibitors. Subsequent ADME studies revealed the pharmacokinetic efficiency of these compounds.