title: 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.
authors.affiliation: SmithKline Beecham Pharmaceuticals, Worthing, West Sussex, UK.
authors.forename: J
authors.initials: J
authors.lastname: Thirkettle
authors.forename: E
authors.initials: E
authors.lastname: Alvarez
authors.forename: H
authors.initials: H
authors.lastname: Boyd
authors.forename: M
authors.initials: M
authors.lastname: Brown
authors.forename: E
authors.initials: E
authors.lastname: Diez
authors.forename: J
authors.initials: J
authors.lastname: Hueso
authors.forename: S
authors.initials: S
authors.lastname: Elson
authors.forename: M
authors.initials: M
authors.lastname: Fulston
authors.forename: C
authors.initials: C
authors.lastname: Gershater
authors.forename: M L
authors.initials: ML
authors.lastname: Morata
authors.forename: P
authors.initials: P
authors.lastname: Perez
authors.forename: S
authors.initials: S
authors.lastname: Ready
authors.forename: J M
authors.initials: JM
authors.lastname: Sanchez-Puelles
authors.forename: R
authors.initials: R
authors.lastname: Sheridan
authors.forename: A
authors.initials: A
authors.lastname: Stefanska
authors.forename: S
authors.initials: S
authors.lastname: Warr
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D005285:Fermentation; D006801:Humans; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D011551:Pseudomonas fluorescens / Q000378:metabolism*; D011714:Pyrans / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D011714:Pyrans; C414127:SB 253514; D010741:Phospholipases A; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase