SB-253514 and Analogues; Novel Inhibitors of Lipoprotein-Associated Phospholipase A₂ Produced by Pseudomonas fluorescens DSM 11579

I. Fermentation of Producing Strain, Isolation and Biological Activity

Abstract

Two new classes of inhibitors of LpPLA₂ have been identified in fermentations of Pseudomonas fluorescens. The two structurally isomeric series differ in the geometry of closure of the bicyclic carbamate and comprise a range of compounds varying only in length of their lipophilic sidechain. The most abundant species were extracted from the cells and purified by silica and C18 chromatography. Members of the more stable class were shown to be potent and selective competitive inhibitors of LpPLA₂.