The anti-atherogenic activity of beauveriolide derivative BVD327, a sterol O-Acyltransferase 2-Selective inhibitor, in apolipoprotein E knockout mice

Taichi Ohshiro, Satoshi Imuta, Ichiro Hijikuro, Hiroaki Yagyu, Takashi Takahashi, Takayuki Doi, Shun Ishibashi, Hiroshi Tomoda

研究成果: Article査読

3 被引用数 (Scopus)

抄録

The fungal 13-membered cyclodepsipeptides, beauveriolides I and III, were previously reported to be atheroprotective activity in mouse models via inhibiting sterol O-acyltransferase (SOAT) activity. A total of 149 beauveriolide derivatives (BVDs) synthesized combinatorially were evaluated in in silico absorption, distribution, metabolism and excretion (ADME) analysis and inhibitory activity toward the two SOAT isozymes, SOAT1 and SOAT2. Hence, only 11 BVDs exhibited SOAT2-selective inhibition. Among these, we chose BVD327, which had the highest ADME score, for further evaluation. BVD327 administration (50mg/kg/d, per os (p.o.)) significantly decreased atherosclerotic lesions in the aorta and heart (25.4±6.9 and 20.6±2.9%, respectively) in apolipoprotein E knockout (Apoe/) mice fed a cholesterol-enriched diet (0.2% cholesterol and 21% fat) for 12 weeks. These findings indicate that beauveriolide derivatives can be used as anti-atherosclerotic agents.

本文言語English
ページ(範囲)951-958
ページ数8
ジャーナルBiological and Pharmaceutical Bulletin
43
6
DOI
出版ステータスPublished - 2020

ASJC Scopus subject areas

  • 薬理学
  • 薬科学

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