Protein-based alignment in 3D QSAR of 26 indole inhibitors of human pancreatic phospholipase A(2)

An automated docking procedure was applied on a series of 26 reversible and competitive indole inhibitors of human pancreatic phospholipase A(2) (hp-P LA(2)). X-ray data of this enzyme are not available and the structure was t hen reconstructed exploiting its protein sequence and the crystallographic data of a bovine pancreatic source. The docking data were used to build a t hree-dimensional quantitative structure-activity relationship (3D QSAR) mod el, established using the comparative molecular field analysis (CoMFA) meth od. This model, joined to the previous one developed for the indole inhibit ors of human non-pancreatic secretory phospholipase A(2) (hnps-PLA(2)), an enzyme involved in inflammation processes, will allow for the selection of new strong anti-inflammatory drugs with negligible side effects, at least a t the level of hp-PLA(2). (C) 2001 Editions scientifiques et medicales Else vier SAS.