The selectivity of beauveriolide derivatives in inhibition toward the two isozymes of acyl-CoA: cholesterol acyltransferase.
The selectivity of synthetic beauveriolide derivatives in inhibition toward the two isozymes of acyl-CoA : cholesterol acyltrasferase (ACAT), ACAT1 and ACAT2, was studied in cell-based assays using ACAT1- or ACAT2-expressing Chinese hamster ovary (CHO) cells. NBV274, 285 and 300 showed ACAT1 selective inhibition similar to that of natural beauveriolides I and III, NBV345 inhibited both isozymes with similar potency, but NBV281, 331 and 249 were found to selectively inhibit the ACAT2 isozyme. The structure-activity relationships indicated that a subtle structural difference in beauveriolide derivatives can affect the selectivity of inhibition of the ACAT isozymes.
Ohshiro
Taichi
T
Graduate School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Matsuda
Daisuke
D
Nagai
Kenichiro
K
Doi
Takayuki
T
Sunazuka
Toshiaki
T
Takahashi
Takashi
T
Rudel
Lawrence Lee
LL
Omura
Satoshi
S
Tomoda
Hiroshi
H