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.
- Acyl-CoA : cholesterol acyltransferase
- Selective inhibition
ASJC Scopus subject areas
- Drug Discovery