The selectivity of beauveriolide derivatives in inhibition toward the two isozymes of acyl-CoA: Cholesterol acyltransferase

Taichi Ohshiro, Daisuke Matsuda, Kenichiro Nagai, Takayuki Doi, Toshiaki Sunazuka, Takashi Takahashi, Lawrence Lee Rudel, Satoshi Omura, Hiroshi Tomoda

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)377-381
Number of pages5
JournalChemical and Pharmaceutical Bulletin
Volume57
Issue number4
DOIs
Publication statusPublished - 2009
Externally publishedYes

Keywords

  • Acyl-CoA : cholesterol acyltransferase
  • Beauveriolide
  • Isozyme
  • Selective inhibition

ASJC Scopus subject areas

  • Chemistry(all)
  • Drug Discovery

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