Discovery of novel secretory phospholipase A2 inhibitors using virtual screen.

Human non-pancreatic secretory phospholipase A2 was reported to be associated with inflammatory diseases and considered as a potential drug target for inflammation and other related disease treatment. Although many human non-pancreatic secretory phospholipase A2 inhibitors were reported, few entered into the drug development stage due to various problems. In this study, we discovered seven novel human non-pancreatic secretory phospholipase A2 inhibitors using virtual screen. Of the 99 compounds tested by continuous fluorescence assay, seven are potent human non-pancreatic secretory phospholipase A2 inhibitors with micromolar IC50 values. Typical molecules include 9-fluorenylmethoxycarbonyl protected α-phenylalanine derivatives and azo compounds, which may serve as novel scaffold for developing potent human non-pancreatic secretory phospholipase A2 inhibitors. These compounds bind to human non-pancreatic secretory phospholipase A2 by interacting with the catalytic calcium ion and the hydrophobic regions in the substrate-binding pocket.