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  • Title: The selectivity of beauveriolide derivatives in inhibition toward the two isozymes of acyl-CoA: cholesterol acyltransferase.
    Author: Ohshiro T, Matsuda D, Nagai K, Doi T, Sunazuka T, Takahashi T, Rudel LL, Omura S, Tomoda H.
    Journal: Chem Pharm Bull (Tokyo); 2009 Apr; 57(4):377-81. PubMed ID: 19336931.
    Abstract:
    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.
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