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

• Published in: Journal of antibiotics 2000/07/25, Vol.53(7), pp.664-669
• Main Authors: THIRKETTLE, JAN, ALVAREZ, EMILIO, BOYD, HELEN, BROWN, MURRAY, DIEZ, EMILIO, HUESO, JUAN, ELSON, STEVE, FULSTON, MARK, GERSHATER, CRAIG, MORATA, MARIA LUISA, PEREZ, PALOMA, READY, SARAH, SANCHEZ-PUELLES, JOSE MARIA, SHERIDAN, ROSE, STEFANSKAC, ANNA, WARR, STEPHEN
• Format: Article
• Language: English
• Subjects: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Animals; Antibiotics (antibacterial agents, antifungal agents); Antibiotics, microbial producers, chemotherapic agents, antiseptics, disinfecting agents; Applied microbiology; Biological and medical sciences; Bridged Bicyclo Compounds, Heterocyclic - isolation & purification; Bridged Bicyclo Compounds, Heterocyclic - metabolism; Bridged Bicyclo Compounds, Heterocyclic - pharmacology; Drug Evaluation, Preclinical - methods; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - metabolism; Enzyme Inhibitors - pharmacology; Fermentation; Fundamental and applied biological sciences. Psychology; Humans; Microbiology; Phospholipases A - antagonists & inhibitors; Phospholipases A2; Pseudomonas fluorescens - metabolism; Pyrans - isolation & purification; Pyrans - metabolism; Pyrans - pharmacology; Rabbits
• ISSN: 0021-8820; 1881-1469
• DOI: 10.7164/antibiotics.53.664

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.