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

doi:10.1248/cpb.57.377

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

PHA - Molecular Pharmaceutical Science

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	377-381
Number of pages	5
Journal	Chemical and Pharmaceutical Bulletin
Volume	57
Issue number	4
DOIs	https://doi.org/10.1248/cpb.57.377
Publication status	Published - 2009

Keywords

Acyl-CoA : cholesterol acyltransferase
Beauveriolide
Isozyme
Selective inhibition

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10.1248/cpb.57.377

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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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T1 - The selectivity of beauveriolide derivatives in inhibition toward the two isozymes of acyl-CoA

T2 - Cholesterol acyltransferase

AU - Ohshiro, Taichi

AU - Matsuda, Daisuke

AU - Nagai, Kenichiro

AU - Doi, Takayuki

AU - Sunazuka, Toshiaki

AU - Takahashi, Takashi

AU - Rudel, Lawrence Lee

AU - Omura, Satoshi

AU - Tomoda, Hiroshi

PY - 2009

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AB - 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.

KW - Acyl-CoA : cholesterol acyltransferase

KW - Beauveriolide

KW - Isozyme

KW - Selective inhibition

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

Abstract

Keywords

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