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: Shunchen Qiu, Fangjin Chen, Ying Liu, Luhua Lai
• Journal: Chemical biology & drug design (Chem Biol Drug Des) Vol. 84 Issue 2 Pg. 216-22 (Aug 2014) ISSN: 1747-0285 [Electronic] England
• PMID: 24612767 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons A/S.

Chemical References

• 9-fluorenylmethoxycarbonyl
• Azo Compounds
• Fluorenes
• Phospholipase A2 Inhibitors
• Phenylalanine
• Phospholipases A2, Secretory

Topics

• Azo Compounds (chemistry, pharmacology)
• Drug Design
• Fluorenes (chemistry, pharmacology)
• Humans
• Molecular Docking Simulation
• Phenylalanine (chemistry, pharmacology)
• Phospholipase A2 Inhibitors (chemistry, pharmacology)
• Phospholipases A2, Secretory (antagonists & inhibitors, metabolism)
• Spectrometry, Fluorescence