Protein-based alignment in 3D QSAR of 26 indole inhibitors of human pancreatic phospholipase A2.

摘要

An automated docking procedure was applied on a series of 26 reversible and competitive indole inhibitors of human pancreatic phospholipase A2 (hp-PLA2). X-ray data of this enzyme are not available and the structure was then reconstructed exploiting its protein sequence and the crystallographic data of a bovine pancreatic source. The docking data were used to build a three-dimensional quantitative structure-activity relationship (3D QSAR) model, established using the comparative molecular field analysis (CoMFA) method. This model, joined to the previous one developed for the indole inhibitors of human non-pancreatic secretory phospholipase A2 (hnps-PLA2), an enzyme involved in inflammation processes, will allow for the selection of new strong anti-inflammatory drugs with negligible side effects, at least at the level of hp-PLA2.