title: ZG-1494 alpha, a novel platelet-activating factor acetyltransferase inhibitor from Penicillium rubrum, isolation, structure elucidation andbiological activity.
abstract: A novel inhibitor of platelet-activating factor (PAF) acetyltransferase, an essential enzyme in the remodeling pathway of platelet-activating factor synthesis, was identified by a high throughout screen of natural product extracts of microbial origin. The compound, ZG-1494 alpha, was isolated from an ethyl acetate extract of a culture broth of Penicillium rubrum through bioassay guided fractionation. The structure of ZG-1494 alpha was determined by spectroscopic methods. A key feature of the structure, which is relatively rare among natural products, is the 5-hydroxy-3-pyrrolin-2-one moiety. A 13C-13C INADEQUATE was utilized to unambiguously determine the regiochemistry of this molecule.
authors.affiliation: Zymogenetics, Seattle, WA 98102, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: West
authors.forename: J
authors.initials: J
authors.lastname: Van Ness
authors.forename: A M
authors.initials: AM
authors.lastname: Varming
authors.forename: B
authors.initials: B
authors.lastname: Rassing
authors.forename: S
authors.initials: S
authors.lastname: Biggs
authors.forename: S
authors.initials: S
authors.lastname: Gasper
authors.forename: P A
authors.initials: PA
authors.lastname: Mckernan
authors.forename: J
authors.initials: J
authors.lastname: Piggott
mesh_terms: D000123:Acetyltransferases / Q000037:antagonists & inhibitors*; D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D018922:HL-60 Cells; D006632:Histamine / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D010407:Penicillium / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000378:metabolism; D011485:Protein Binding; D011760:Pyrrolidinones / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D011965:Receptors, Glucocorticoid / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D010972:Platelet Activating Factor; D011760:Pyrrolidinones; D011965:Receptors, Glucocorticoid; C103027:ZG 1494alpha; D006632:Histamine; D000123:Acetyltransferases; C046035:1-alkylglycerophosphocholine acetyltransferase