Study of indole derivative inhibitors of Cytosolic phospholipase A(2)alpha based on Quantitative Structure Activity Relationship
Cytosolic phospholipase A(2)alpha, one of the three subtypes of Cytosolic phospholipase A(2) (alpha, beta and gamma), is deemed to play an important role in the arachidonate pathway. Due to the rate-limiting provider for proinflammatory mediators, it is a particularly attractive target for drug development. Studies have revealed that indol derivate compounds can inhibit the activities of Cytosolic phospholipase A(2)alpha. However, few papers on the relationship between the molecular structure and the activity of inhibitor were reported. In this study, the Quantitative Structure Activity Relationship (QSAR) of indole derivates has been performed based on the dataset of 49 compounds. By using stepwise multiple linear regression, 5 descriptors were selected from 1777 molecular descriptors, including GGI5 (Topological charge index G(5)), TIE(dssC) (sum of E-State of atom type dssC: vertical bar S-2(dssC)), RDF115a (the atomic Sanderson ALOGP), RDF100c (the atomic charge), and RDF065p (the atomic polarizability). Subsequently, Partial Least Squares (PLS), Artificial Neural Networks (ANN) and Support Vector Machine (SVM) were adopted to build the QSAR model, respectively. The independent test indicated that the SVM can give the best statistical results. And indole derivative inhibitors activity might be related to global charge transfers, carbon atoms type linked benzyl sulfonamide and molecule geometrical the distance distribution. Crown Copyright (C) 2011 Published by Elsevier BM. All rights reserved.
quantitative structure activity relationships partial least squares artificial neural networks support vector machine cytosolic phospholipase a(2)alpha inhibitor