Pyripyropenes, novel ACAT inhibitors produced by Aspergillus fumigatus. IV. Structure elucidation of pyripyropenes M to R.
Six new pyripyropenes, M to R, were isolated from the ethyl acetate extracts of the jar fermentation broth of Aspergillus fumigatus FO-1289-2501. Structural elucidation indicated that all the pyripyropenes have the same pyridino-alpha-pyrone sesquiterpene core as pyripyropenes A to L. Among them pyripyropene M showed the most potent inhibition against acyl-CoA : cholesterol acyltransferase activity with an IC50 value of 3.80 microM in rat liver microsomes, but pyripyropenes N to R showed moderate inhibitory activity (IC50 11.0 approximately 78.0 microM).
Tomoda
H
H
Research Center for Biological Function, Kitasato University, Kitasato Institute, Tokyo, Japan.
Tabata
N
N
Yang
D J
DJ
Namatame
I
I
Tanaka
H
H
Omura
S
S
Kaneko
T
T
D000818:Animals; D001232:Aspergillus fumigatus / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D012717:Sesquiterpenes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D011725:Pyridines; D012717:Sesquiterpenes; C099308:pyripyropene M; C099309:pyripyropene N; C099310:pyripyropene O; C099311:pyripyropene P; C099312:pyripyropene Q; D002785:Sterol O-Acyltransferase