Purpactins, new inhibitors of acyl-CoA:cholesterol acyltransferase produced by Penicillium purpurogenum. III. Chemical modification of purpactin A.
Acylated derivatives of the C-1' and/or C-11 hydroxy group(s) of penicillide were synthesized and their inhibitory activity against acyl-CoA:cholesterol acyltransferase (ACAT) was studied. Introduction of long acyl group into either or both hydroxy residue(s) decreased the inhibitory activity. A small acyl moiety such as acetyl or n-butyryl at the C-1' hydroxy group is responsible for potent inhibitory activity against ACAT. The 1'-O-acetyl-11-O-tetrahydropyranyl derivative (11-O-2''-tetrahydropyranylpurpactin A) showed high selectivity (cytotoxic dose vs. effective dose) in a cell assay using J774 macrophages.
Nishida
H
H
Research Center for Biological Function, Kitasato Institute, Tokyo, Japan.
Tomoda
H
H
Cao
J
J
Araki
S
S
Okuda
S
S
Omura
S
S
D000818:Animals; D002460:Cell Line; D006571:Heterocyclic Compounds / Q000378:metabolism*; D006575:Heterocyclic Compounds, 3-Ring; D008264:Macrophages / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*
D006571:Heterocyclic Compounds; D006575:Heterocyclic Compounds, 3-Ring; C068086:purpactin A; D002785:Sterol O-Acyltransferase