title: Discovery of novel secretory phospholipase A2 inhibitors using virtual screen.
abstract: 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.
authors.affiliation: BNLMS, State Key Laboratory of Structural Chemistry for Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
authors.forename: Shunchen
authors.initials: S
authors.lastname: Qiu
authors.forename: Fangjin
authors.initials: F
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Luhua
authors.initials: L
authors.lastname: Lai
mesh_terms: D001391:Azo Compounds / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D005449:Fluorenes / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D062105:Molecular Docking Simulation; D010649:Phenylalanine / Q000737:chemistry / Q000494:pharmacology; D064801:Phospholipase A2 Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D054497:Phospholipases A2, Secretory / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013050:Spectrometry, Fluorescence
chemical_list: C496789:9-fluorenylmethoxycarbonyl; D001391:Azo Compounds; D005449:Fluorenes; D064801:Phospholipase A2 Inhibitors; D010649:Phenylalanine; D054497:Phospholipases A2, Secretory
keywords: continuous fluorescence assay; drug design; novel inhibitor; secretory phospholipase A2; virtual screen