Study of indole derivative inhibitors of Cytosolic phospholipase A2α based on Quantitative Structure Activity Relationship

Cytosolic phospholipase A2α, one of the three subtypes of Cytosolic phospholipase A2 (α, β and γ), 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 A2α. 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 G5), TIE(dssC) (sum of E-State of atom type dssC: ¦2S(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.