Terpendoles, novel ACAT inhibitors produced by Albophoma yamanashiensis. I. Production, isolation and biological properties.
A series of new acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors termed terpendoles were isolated from the culture broth of a fungal strain FO-2546 which was proposed to belong to a new genus designated as Albophoma yamanashiensis. Among four structurally related terpendoles, terpendole C showed the most potent ACAT inhibitory activity with an IC50 value of 2.1 microM in an in vitro enzyme assay, followed by terpendoles D (IC50: 3.2 microM), A (15.1 microM) and B (26.8 microM). Evaluation of their ACAT inhibition in the cell assay using J774 macrophages indicated that terpendole D exhibited the highest specificity (cytotoxicity vs. ACAT inhibition) among microbial ACAT inhibitors we discovered so far.
Huang
X H
XH
Research Center for Biological Function, Kitasato Institute, Tokyo, Japan.
Tomoda
H
H
Nishida
H
H
Masuma
R
R
Omura
S
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000302:isolation & purification* / Q000494:pharmacology*; D002788:Cholesterol Esters / Q000378:metabolism; D004224:Diterpenes / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D005285:Fermentation; D005658:Fungi / Q000737:chemistry* / Q000378:metabolism*; D007211:Indoles / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*
D000900:Anti-Bacterial Agents; D002788:Cholesterol Esters; D004224:Diterpenes; D007211:Indoles; C092161:terpendole A; C092162:terpendole B; C092163:terpendole C; C092164:terpendole D; D002785:Sterol O-Acyltransferase