SB-253514 and analogues; Novel inhibitors of lipoprotein-associated phospholipase A(2) produced by Pseudomonas fluorescens DSM 11579 - I. Fermentation of producing strain, isolation and biological activity

Two new classes of inhibitors of LpPLA(2) have been identified in fermentat ions of Pseudomonas fluorescens. The two structurally isomeric series diffe r in the geometry of closure of the bicyclic carbamate and comprise a range of compounds varying only in length of their lipophilic sidechain. The mos t abundant species were extracted from the cells and purified by silica and C18 chromatography. Members of the more stable class were shown to be pate nt and selective competitive inhibitors of LpPLA(2).