Quinoline-4-methyl esters as human nonpancreatic secretory phospholipase A₂ inhibitors

Yiran Wu; Zheng Chen; Ying Liu; Lanlan Yu; Lu Zhou; Suijia Yang; Luhua Lai

doi:10.1016/j.bmc.2011.04.039

Quinoline-4-methyl esters as human nonpancreatic secretory phospholipase A₂ inhibitors

Bioorg Med Chem. 2011 Jun 1;19(11):3361-6. doi: 10.1016/j.bmc.2011.04.039. Epub 2011 Apr 22.

Authors

Yiran Wu¹, Zheng Chen, Ying Liu, Lanlan Yu, Lu Zhou, Suijia Yang, Luhua Lai

Affiliation

¹ BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

PMID: 21555224
DOI: 10.1016/j.bmc.2011.04.039

Abstract

A series of novel fused heterocycle methyl esters were designed and synthesized as human nonpancreatic secretory phospholipase A₂ (hnps-PLA₂) competitive inhibitors. Among the 22 synthesized compounds, 17 quinoline-4-methyl esters displayed hnps-PLA₂ inhibition activity in the in vitro bioassay. The IC₅₀ value for the best compound 3o was 1.5 μM. The structure-inhibition-activity relationships of the compounds were studied using molecular docking.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Computer Simulation
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology
Esters
Group II Phospholipases A2 / antagonists & inhibitors*
Group II Phospholipases A2 / metabolism
Humans
Quinolines / chemical synthesis
Quinolines / chemistry*
Quinolines / pharmacology
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Esters
Quinolines
methyl 6-methoxy-2-phenethylquinoline-4-carboxylate
quinoline
Group II Phospholipases A2