ZG-1494 alpha, a novel platelet-activating factor acetyltransferase inhibitor from Penicillium rubrum, isolation, structure elucidation andbiological activity.
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.
West
R R
RR
Zymogenetics, Seattle, WA 98102, USA.
Van Ness
J
J
Varming
A M
AM
Rassing
B
B
Biggs
S
S
Gasper
S
S
Mckernan
P A
PA
Piggott
J
J
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
D004791:Enzyme Inhibitors; D010972:Platelet Activating Factor; D011760:Pyrrolidinones; D011965:Receptors, Glucocorticoid; C103027:ZG 1494alpha; D006632:Histamine; D000123:Acetyltransferases; C046035:1-alkylglycerophosphocholine acetyltransferase